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| # | nctid | description | label |
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| 1 | NCT02464748 | MND is often referred to as amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease. | ALS |
| 2 | NCT00362362 | OBJECTIVE:||The causes of sporadic motor neuron diseases, primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are unknown. Genes have been identified for some forms of familial motor neuron diseases. We don't know whether genes also play a role in sporadic motor neuron disease, for example through risk-factor genes or by the interaction of multiple genes as a complex genetic disorder. Identification of genetic contributions to sporadic motor neuron diseases requires analysis of DNA from patients.||The goal of this protocol is to collect blood samples from patients with motor neuron disease for creation of cell lines to bank in a repository created through an NINDS initiative. The cell lines will be used for DNA extraction. The repository provides anonymized samples of patient DNA or cell lines to investigators who are seeking to define genetic causes, contributions, and susceptibilities to neurological disorders. DNA and cell lines created from the blood sample are stripped of patient identifiers and stored indefinitely. A limited amount of clinical data, termed the clinical data elements, will be available for each coded sample. The samples will only be available for research. The results of testing will not be communicated to the patient.||STUDY POPULATION:||All patients will be enrolled in a primary protocol for the study of motor neuron diseases at NIH. This protocol will serve as a secondary protocol for sample collection and reporting of clinical data elements. Patients with Primary lateral sclerosis must meet the diagnostic criteria for PLS proposed by Pringle and patients with ALS must fulfill the revised El Escorial criteria for probable or definite ALS.||DESIGN:||Determination of diagnosis and eligibility will be carried out as part of the primary protocol. Patients will be informed of the DNA sample repository and its purpose. After informed consent is obtained, 2 tubes of blood will be drawn and assigned a unique identifier code. The coded samples, and a clinical data element form will then be sent to the repository, which will extract DNA and prepare cell lines. The identities of the subjects will not be stored. An aliquot of the sample will be forwarded to the associate investigator to look for disease associations with genetic markers.||OUTCOME MEASURES:||There is no specific outcome measure for this protocol. The samples will be made accessible to a wide variety of researchers seeking to determine the causes of motor neuron diseases and other neurological disorders through the repository's contract with NINDS. | ALS |
| 3 | NCT03154450 | Non-invasive ventilation (NIV) use in patients with motor neurone disease (MND) who develop respiratory failure can improve symptoms and survival. Initiation of NIV can be difficult for patients and those who do not adequately adhere to the regime fail to gain benefit. This study will evaluate the use of EncoreAnywhere: a system which collects data on NIV use and effectiveness from the NIV machines and transmits it to the MND care team for review.||This study is a pilot, feasibility study. It is a randomised controlled trial comparing the use of EncoreAnywhere with usual care. Up to 40 patients with MND about to start NIV will be recruited. All patients will have the EncoreAnywhere system installed on their NIV machine for the first three months of NIV use. Half the patients will be randomised to the intervention arm which will allow the MND care team to review the information sent from the device regularly during the study. Data will be collected from the other patients but not reviewed by the clinical team. All patients will receive usual care.||Data will be collected by three methods. Data collected from the EncoreAnywhere system will examine adherence and effectiveness of ventilation. The main outcome of interest is adherence to NIV at three months. Data will be collected from patients (patient symptoms and quality of life) using questionnaires (at baseline, one and three months) and collected from information recorded in the patients' notes as part of usual care. Data will also be collected to examine feasibility e.g. recruitment and retention rates. A subset of patients will be invited to undergo overnight oximetry at 1 and 3 months to examine NIV effectiveness.||The aims of the research are to establish the level of adherence and effectiveness of NIV during initiation and factors that may impact on adherence and effectiveness and also evaluate the feasibility and impact using EncoreAnywhere on the Sheffield MND team working pattern, the clinical and cost implications for a full service. | ALS |
| 4 | NCT03487263 | The objectives of this study are to determine:||The safety, tolerability and immunogenicity of IC14 in patients with motor neurone disease (MND).|The pharmacokinetics and pharmacodynamics of IC14 in patients with MND.|The preliminary effect of IC14 on the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) in patients with MND.|The preliminary effect of IC14 on forced vital capacity (FVC) and other clinical markers of disease severity in patients with MND.|The preliminary effect of IC14 on patient-reported outcome measures.|The preliminary effect of IC14 on disease biomarkers.||Ten patients with MND will be sequentially assigned to receive one of two dose regimens of IC14 in an unblinded manner:||For the initial 3 patients: IC14 at a dosage of 2 mg/kg on Study Day 1, then 1 mg/kg once daily on Study Days 3-5 for 4 total doses.|For the subsequent 7 patients: IC14 at a dosage of 4 mg/kg on Study Day 1, then 2 mg/kg once daily on Study Days 2-4 for 4 total doses.||Study participation will continue until 28 days after the last dose of study drug. | ALS |
| 5 | NCT04454892 | With the development of supportive measures, the natural history of ALS has changed. Researchers compared the natural history of ALS patients from 1999-2004 and 1984-1998 and found that the median survival time was significantly longer in the former than in the latter (4.32 years vs. 3.22 years) and that the disease progression was slower in the former, even after adjusting for other confounding factors. Although previous studies have provided reference for the diagnosis and treatment of ALS, the etiology of ALS is still unknown, and the relevant clinical features and natural history of ALS still lack the verification of large samples. Therefore, the research on the natural history of ALS is of great significance to further increase the understanding of ALS and provide new evidence for the diagnosis and treatment of ALS. | ALS |
| 6 | NCT02852278 | The patient activities of daily living for amyotrophic lateral sclerosis survey (PADL-ALS, Appendix B) is a patient-centric revision of the standard revised ALS functional rating scale used in clinical trials, the ALSFRS-R. The PADL-ALS was developed based on patient interviews, and patient focus groups. The ALSFRS-R is made up of 12 categories detailing various activities of daily living and includes six bulbar-respiratory functions, three upper extremity functions (writing, cutting food, and dressing), and three gross motor functions (walking, climbing, and turning in bed). Each activity is recorded to the closest approximation from a list of five choices, scored 0-4, with the total score ranging from 48 (normal function) to 0 (no function). The PADL-ALS includes questions from the ALSFRS-R, with revisions to make the questions easier to understand. In addition the PADL-ALS contains a question about pain; a question about emotional lability; and a general non-denominational question about faith. The survey will be composed of two parts, the initial survey, and then monthly follow up surveys. The initial survey will include the PADL-ALS with additional questions about symptom onset, date of diagnosis, initial region involved, patient impression of diagnosis, general demographic questions (age, gender, race, ethnicity, education), and medications related to their diagnosis of motor neuron disease.||The survey data will be stored by the Rare Diseases Clinical Research Network's Data Management and Coordinating Center (DMCC) at the University of South Florida. Upon conclusion of the study period, the data will be sent to Jeffrey Statland, MD, University of Kansas Medical Center (Study Chair) and Michael Benatar, MD, PhD, University of Miami (CReATe Consortium PI). All data collected will be sent to the database of Genotypes and Phenotypes (dbGaP) to be stored indefinitely. | ALS |
| 7 | NCT01776970 | CANALS project has as a main objective to analyse the safety profile, tolerability and efficacy of a Cannabis Sativa (Sativex) derivative on patients affected by spasticity due to motor neuron disease.||Muscular rigidity (or spasticity) is a symptom that affects many patients with motor neuron disease, concurring to reduce personal autonomy, patients' quality of life and can potentially cause secondary symptomatology (as pain or secondary muscular retractions). Currently available anti-spasticity drugs are often unsatisfactory and their pharmacological action can cause weakness as a secondary effect. There many arguments supporting the use of cannabinoid derivatives in motor neuron diseases. Cannabinoids receptor is expresses both in the brain and in the spinal cord. In animal models cannabinoids have an anti-spasticity effect. Moreover recent studies on ALS animal models demonstrated a neuroprotective effect of cannabinoids, including the preservation of the motor ability and a survival increase of the treated animals. Recently many clinical trials (some of them performed at the Neurological Division of San Raffaele Hospital) demonstrated cannabinoid efficacy on spasticity in Multiple Sclerosis patients. CAnnabinois would be able to reduce spasticity with no secondary weakness effect on treated patients. The results of these studies led to the drug approval in certain countries and by the European Community for the treatment of spasticity in Multiple Sclerosis.||The aim of this study is to analyze the safety, tolerability and efficacy profile of a Cannabis Sativa (Sativex) derivative on patients affected by spasticity due to motor neuron disease ( Amyotrophic Lateral Sclerosis and Primary Lateral Sclerosis). The study will be performed along 7 weeks. During the first week will be asked patients to note down in the clinical diary elements related to their symptomatology. Afterwards patients will be randomized in two groups: drug-treated and placebo treated. The study will be followed by a 6-weeks open-label phase during which all patients will receive the active drug (Phase B) | ALS |
| 8 | NCT01772602 | The National ALS Registry's Research Notification System allows person with ALS to participate in clinical trials. | ALS |
| 9 | NCT01143428 | Objective||Primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) are motor neuron disorders with different phenotypes that progress at very different rates. ALS is a rapidly progressive disease with a median survival less than 5 years. Patients with PLS have a slowly progressive course with a normal lifespan. One hypothesis is that oxidative stress affects the way in which different motor neuron disorders progress. To test this hypothesis, exposures to putative triggers of oxidative stress and biomarkers that may reflect oxidative stress will be assessed in patients with motor neuron disorders. A multicenter effort (the COSMOS study) has been initiated to accumulate sufficient numbers of ALS patients to address this hypothesis. As an add-on study, PLS patients will also be assessed in the multicenter effort. The objective of this protocol is to enroll PLS patients in this multicenter effort. The goal is to assess environmental factors and markers of oxidative stress in patients with established PLS.||Study Population||15 adult patients with PLS who have symptoms of pure upper motor neuron dysfunction for at least 5 but not more than 15 years.||Design||Patients will undergo a standard battery of clinical, physiological, and cognitive screening tests at enrollment, with scheduled follow-up evaluation visits every 12 months for 36 months. Blood and urine samples will be sent to collaborators at Columbia University for analysis of markers of oxidative injury and genetic risk factors. Patients will complete a self-administered nutritional survey and will be interviewed by phone by Columbia University investigators using questionnaires to assess environmental, occupational, lifestyle and psychosocial factors thought to be triggers of oxidative stress.||Outcome Measures||The Columbia University collaborators will combine data from several centers in a regression model correlating the slope of decline of the ALS-FRS score with an index of oxidative stress. | ALS |
| 10 | NCT02360891 | This is a prospective observational multicentric French study of a cohort of 1000 ALS patients, 100 neurological controls and 200 healthy controls followed from the first signs to the end of the disease.||The aim of the present study is therefore to determine the clinical, biological, imaging, and electrophysiological biomarkers of prognosis of survival without events (i.e. severe comorbidity, 24 hours of non invasive ventilation, tracheotomy).||Secondary objectives will notably include i) the biomarkers of disease progression ii) biomarkers of diagnosis as compared with controls iii) the determination of the different endophenotypes according to the prognosis, the genetic profiles and the initial clinical presentations. Criteria of assessment will notably include detailed medical history, habitus, past and present treatments, vascular risk factors, ALSFRS-R, muscular testing, respiratory parameters including early nocturnal saturation and apneal profile, the detailed and predetermined clinical presentations, extensive cognitive and behavioral examination, extensive blood, cerebrospinal fluid, urines biological tests, genetic analyses, multiple brain and spinal MRI sequences, and electrophysiological tests (i.e. electromyogram, MUNIX, triple stimulation). Invasive tests will be optional (i.e. lumbar puncture, skin biopsies, muscular biopsies).||The large number of patients will allow in depth statistical analyses, notably to establish decisional trees (CHAID). | ALS |
| 11 | NCT02166944 | The investigators will assess the ALSFR-s in ALS patients at start, 1, 3, 6 and 12 months and correlate the score to the neurological outcome of the patients with and without tamoxifen treatment at dose of 40mg daily for one year.||The study will be able to prove the investigators hypothesis: Tamoxifen, a protease and autophagy enhancer, has synergic effect with riluzole in ALS patients to slowing the progression of neurological dysfunction, and respiratory insufficiency. | ALS |
| 12 | NCT03444428 | The stiffness of the arterial wall is highly relevant to cardiovascular disease. Large elastic arteries and smaller muscular conduit arteries become stiffer with ageing, a process that is accelerated in the presence of cardiovascular disease. Arterial stiffness increases also with various disease states, including hypertension, diabetes mellitus, obesity, smoking, hypercholesterolemia, and kidney disease. Numerous techniques have been developed to measure arterial stiffness, either in single vessels or in entire muscular arterial trees. These techniques have increasingly been shown to improve stratification of cardiovascular risk and risk reduction beyond that provided by conventional risk factors. Furthermore, large artery stiffness, measured via carotid-femoral pulse wave velocity, independently predicts the risk of cardiovascular events in both clinical and community-based cohorts.||Abnormalities in arterial stiffness have been noted in disorders characterized by hypoxia with or without hypercapnia. These abnormalities could be driven by the risk factors for those conditions (e.g. cigarette smoke, obesity). In COPD, all studies are consistent showing a significant increase in arterial stiffness compared with ex-smokers without airway obstruction and nonsmoker healthy control subjects. The severity of airway obstruction is consistently related to arterial stiffness in COPD. Furthermore, airflow limitation arising from cigarette smoking, but not airflow limitation in non-smokers, was associated with arterial stiffness in a general population independently of established risk factors. The presence of OSA was associated with higher arterial stiffness indices independent of major confounders. In this context, OSA is associated with increased arterial stiffness independent of blood pressure.||Non invasive ventilation has been shown to reduce arterial stiffness in obstructive sleep apnea. In particular, there are studies that have examined the impact of continuous positive airway pressure (CPAP) on arterial stiffness (measured with pulse wave velocity) in OSA patients. Other studies have examined changes in arterial stiffness (measured with other than pulse wave velocity method) after treatment of OSA with CPAP. Furthermore, to the best of our knowledge no investigation exists on the impact of non invasive bilevel positive airway pressure ventilation on arterial stiffness in neuromuscular disease.||The Lane Fox Unit, the UK's largest weaning, rehabilitation and home ventilation unit, is treating neuromuscular patients. In neuromuscular disease, especially in MND, confounding factors as obesity, cigarette smoke, hypertension, and diabetes mellitus can be excluded. This gives the opportunity to determine whether hypoxemia and/or hypercapnia alone cause arterial stiffness. Furthermore, in this pilot study it will be investigated whether non invasive ventilation has any effect on arterial stiffness in MND patients. | ALS |
| 13 | NCT04454840 | This is a single-center, open-label clinical study to evaluate the safety and effectiveness of intravenous infusion of plasma from healthy young people for the treatment of amyotrophic lateral sclerosis. The main outcome indicators are the record of adverse reactions and the rate of change of amyotrophic lateral sclerosisFunctional Rating Scale score. The secondary outcome indicators include survival time-time to the end event (death, tracheotomy, continuous ventilator dependence), forced vital capacity (FVC), recognition Knowledge function evaluation (ECAS score). | ALS |
| 14 | NCT00818389 | Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disorder that results in progressive wasting and paralysis of voluntary muscles.||In this double blind, randomized, placebo-controlled clinical trial, researchers will evaluate the safety and effectiveness of the drug lithium given in combination with riluzole, a drug commonly used to treat ALS, compared to a placebo given in combination with riluzole.||Approximately 250 participants will be recruited from multiple centers, in the US and Canada, that belong to the Northeast ALS Consortium (NEALS) and the Canadian ALS Clinical Trials and Research Network (CALS). Enrollment will occur in stages. Initially 84 participants will be enrolled in the trial. An interim analysis using available data will occur after the 84th participant is enrolled. During this time, the Data and Safety Monitoring Board (DSMB) appointed by the National Institutes of Health (NIH) may decide to stop the trial for efficacy or futility reasons or to stop enrollment and request that follow-up continue with the 84 participants already enrolled in the trial, or the DSMB may decide to continue enrollment.||Participants will be randomized to one of two arms of the study. Arm one will receive lithium and riluzole. Arm two will receive riluzole and placebo (an inactive substance). All participants will be receiving riluzole. After screening and randomization, participants will be followed every 4 weeks for the first 12 weeks. Subsequent in-person visits will occur every 8 weeks with a final visit at week 52. Between in-person visits, telephone interviews will take place every 4 weeks to administer the Amyotropic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) questionnaire. A follow-up telephone interview will occur at week 56 (off study medication) to review adverse events. The primary outcome measure is disease progression as measured by the ALSFRS-R questionnaire. Participants randomized to placebo whose disease progresses will be crossed over to lithium for the remaining period of the study (up to 52 weeks total).||Duration of the study for participants is 56 weeks which includes 52 weeks of treatment and a followup telephone interview at week 56. | ALS |
| 15 | NCT00324454 | Cramps in MNDs are believed to occur as a result of high-frequency burst firing of alpha motor neurons. Levetiracetam inhibits burst firing in epileptic rat hippocampus. Levetiracetam has never been tested against cramps in humans; however, it has helped another condition believed to result from burst firing of a motor nerve: hemi-facial spasm.||The mechanisms underlying spasticity in MNDs likely involve imbalance between excitatory and inhibitory influences on the alpha motor neurons. Levetiracetam may modulate these influences in a number of ways, including reducing the effects of zinc and beta-carbolines in GABA and glycine receptors. Levetiracetam reduces phasic (but not tonic) spasticity in patients with multiple-sclerosis.||Levetiracetam may have neuroprotective properties. In a model of cerebral ischemia induced by occlusion of the rat internal carotid artery, pre-treatment with levetiracetam reduced infarct size in a dose-dependent manner. In rats injected with kainic acid to induce calcium overload, oxidative stress and neurotoxicity, pretreatment with levetiracetam offset kainic acid's effects. The mechanisms for these effects may relate to levetiracetam's ability to influence calcium currents, or its ability to increase the release of growth factors from astrocytes, mechanisms that would be relevant in MNDs. Levetiracetam's ability to inhibit histone deacetylase may also help slow MNDs progression.||OBJECTIVES: 1. Assess the safety and tolerability of levetiracetam over 9 months in patients with MNDs. 2. Determine whether treatment with levetiracetam is associated with a reduction in cramps, spasticity or motor neuron disease progression.||METHODS:Open-label, Phase 2 trial of 20 adult patients with MNDs (ALS, PLS or PMA) at Duke University ALS Clinic. Eligible patients have cramps with average severity 50/100 points, are able to provide informed consent, have normal renal functions and are on a stable riluzole dose. Exclusions include pregnancy, unstable mental illness, dementia, drug abuse or non-compliance. The first 3 months of the study are a baseline period. Over the remaining 9 months, patients take levetiracetam at increasing doses up to 3000mg per day. Outcome measures include adverse events, tolerability,cramp-pain-severity score, cramp-frequency score, modified Ashworth Spasticity Score, Penn Spasm Score, FVC, ALSFRS-R and MMT. | ALS |
| 16 | NCT04518540 | In this proposed study, the investigators will evaluate the safety and efficacy of Lipoic acid in treatment of ALS. The study will recruit 150 ALS patients, then these patients will be randomized to lipoic acid group or control group (75 patients per arm) for 6 courses for about 5 months. Clinical efficacy and safety assessment will be done at screen/baseline, 3th course and 6th course. The specific aims are to compare lipoic acid versus placebo on: (1) Lipoic acid could improve the motor function, delay the disease progression and extend survival time in patients with ALS, measured by the ALSFRS-R Scale, ROADS Scale, upper motor neuron Scale, Muscle strength Scale and Electromyography; (2) Lung function will be collected to prove the hypothesis lipoic acid may help respiratory function. (3) Safety index including blood and urine routine, liver and kidney function, coagulation index will be recorded. | ALS |
| 17 | NCT01950910 | Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by progressive degeneration of motor neurons, muscle atrophy and paralysis. There is no reliable early diagnostic test for ALS making identification of the disease difficult at its earliest stages. Early detection is critical to the initiation of early neuroprotective therapy. By the time a reliable diagnosis can be made, substantial damage to motor neurons and muscle has already occurred. The purpose of the current project is to establish a bank of blood samples (serum and protein/RNA/DNA from blood cells) and CSF for use in the development of an early diagnostic test for ALS and to better understand the progression of this disease.||Samples from patients that have a confirmed or unknown diagnosis of motor neuron disease will be examined. ALS and suspected neuromuscular disease (control) samples will be collected for comparison. Investigators will examine various biochemical, metabolic and genetic markers from these samples in hopes of finding differences in the expression between control subjects and ALS patients and how these biomarkers vary during disease progression. Participants will be asked to complete an optional questionnaire to collect data including medication and vitamin use and medical and disease history. This data will be linked to the patient's samples; however, all samples will be deidentified and coded to avoid the possibility of linking results to the patient. Results will not be stored in the patient's medical record. | ALS |
| 18 | NCT03705390 | Amyotrophic Lateral Sclerosis (ALS) belongs to a wider group of disorders known as motor neuron diseases and mainly involves the nerve cells (neurons) in the body. Voluntary muscles produce movements like chewing, walking and talking. ALS is caused by gradual deterioration (degeneration) and death of these motor neurons. The disease is progressive, meaning the symptoms get worse over time and most people with ALS die from respiratory failure, usually within 3 to 5 years from when the symptoms first appear. Currently there is no cure for ALS and no effective treatment to halt or reverse the progression of the disease (National Institute of Neurological Disorders and Stroke, Fact Sheet).||The aim of this study is to explore the safety and acceptability of a type of low molecular weight dextran sulfate called ILB.||The investigators will invite 15 patients to take part from a single centre in the UK. Participants will be closely monitored for any side-effects; for changes in ALS symptoms and on quality of life during and after the study.||The trial period for patient participation is maximum 56 weeks (12 months), ILB injections will be administered once weekly for up to a maximum of 48 weeks. | ALS |
| 19 | NCT03293394 | Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Current drugs approved for ALS treatment only modestly slow disease progression.||Transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebral excitability in several neurodegenerative disorders and modulate intracortical connectivity measures.||In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with amyotrophic lateral sclerosis and modulate intracortical connectivity, at short and long term.||Subjects will be randomized in two groups, one receiving a 10 day (5 days/week for 2 weeks) treatment with anodal bilateral motor cortex tDCS and cathodal spinal tDCS and the other receiving sham stimulation with identical parameters. After the intervention, patients will be reassessed with a clinical and neurophysiological evaluation at 2 weeks, 2 months and 6 months after treatment. Furthermore, blood neurofilaments will be measured at each time point.||Clinical evaluation will include the ALSFRS-R, ALSAQ-40, CBI, EQ-5D-5L, muscle strength evaluated with the MRC scale.||Neurophysiological evaluation will include measures of intracortical connectivity, evaluated with transcranial magnetic stimulation (TMS) as short interval intracortical inhibition (SICI-ICF), long interval intracortical inhibition (LICI), short interval intracortical facilitation (SICF). | ALS |
| 20 | NCT03536962 | Since April 2010 a quarterly follow-up is available for patients with ALS at Geneva University Hospitals. It takes place in the outpatient unit of the Department of Neurology, and includes interventions by the multidisciplinary team of the " Center for Amyotrophic Lateral Sclerosis and related diseases ". This new tracking method can help improving quality of life of patients and their families by adapting medical care, proposing communication aids, facilitating access to specialized examinations and anticipating pulmonary, nutritional and neurologic complications. Moreover, it speeds up administrative procedures, improves the flow of information between medical teams inside and outside the hospital and it allows and encourages discussion about advanced directives.||Since June 2012, the multidisciplinary follow-up is monitored through a Cohort study that was approved by the ethical committee (NAC 11-062R). We collect clinical examination findings, anthropometric evaluation, blood analyses, pulmonary function tests, respiratory muscle strength, arterial blood gases, nocturnal oximetry, and evaluation by occupational therapists and by physiotherapists on a quarterly basis. Nerve conduction studies are done at the beginning of the follow-up to identify the degree and extent of loss of upper and lower motoneurons in ALS and to help guiding the diagnosis. MRI and analysis of cerebrospinal fluid are also acquired at the beginning of the follow-up in order to rule out other diagnoses which can mimic ALS. Definite, probable or possible ALS is defined according to the Revised El Escorial and Awaji criteria [16-17]. Patients are referred to a genetic counselor who helps making informed decisions regarding genetic issues. The data collected are inserted into the Secu-Trial database, which is managed by an assistant provided by the Clinical Research Center. | ALS |
| 21 | NCT01530438 | Objectives : the investigators aim to study the clinical profile and magnitude of cognitive disturbances, measure brain metabolism and assess cerebral atrophy in patients with ALS. The relationships between cognitive, metabolic and anatomical data will be determined by the correlation method. In addition, pathological studies will be carried out in deceased patients having given their consent in advance, in order to quantify the neuronal loss and UBIs.||Methods : the investigators plan to recruit 60 patients with ALS, 10 patients with ALS/FTD (the diagnosis of dementia will rest on clinical data and formal neuropsychological testing) and 20 normal control subjects. The ALS patients will be divided into 2 subsets on the basis of a preliminary neuropsychological work-up, according to the presence or absence of "subclinical cognitive impairment" as defined by abnormal scoring on tests not meeting the criteria for dementia. In a second testing session carried out at the same time, a comprehensive assessment of memory, behaviour and emotional changes will be done. All subjects will then undergo morphological magnetic resonance imaging (MRI), resting-state functional MRI and 18-fluorodeoxyglucose positron emission tomography (18FDG-PET). Whenever possible, a second testing session will be carried out 9 to 12 months later in order to quantify the cognitive deterioration, if any, and to find early predictors of the evolution towards dementia. In deceased patients, the location and extent of neuronal loss will be determined, as well as the location and number of UBIs.||Results and clinical relevance : this study is intended to improve our knowledge of the clinical phenotype of ALS, and particularly to learn more about the extent of cognitive, behavioural and emotional changes in this disease. This could in turn shed some further light on the relationships between ALS and FTD. | ALS |
| 22 | NCT03508453 | This will be a placebo-controlled, double-blind, parallel-group comparison.||Fifty patients with rapidly progressive ALS will be randomised to receive one of the following regimens:||IC14 4 mg/kg given intravenously twice weekly for 12 weeks; or|Identical-appearing placebo given intravenously twice weekly for 12 weeks. There will be an interim safety review by an independent Data Safety Monitoring Board after the initial 20 subjects have completed 4 weeks and 8 weeks of treatment. Study observation will continue until 12 weeks after the last dose of study drug.||The primary endpoint is:||• Treatment-related change in disease biomarker profiles [e.g., neurofilaments (Nf), urinary p75 neurotrophin receptor (p75NTR), cytokines, and soluble CD14].||The secondary endpoints are:||Safety, tolerability and lack of immunogenicity of IC14.|Treatment-related change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).|Treatment-related change in respiratory function by seated forced vital capacity (FVC) parameters.|Treatment-related change in inspiratory muscle strength by sniff nasal pressure (SNP) test.|Treatment-related change in quality of life by the ALS Specific Quality of Life-Revised (ALSSQOL-R) score.|Treatment-related change in cognitive function by Edinburgh Cognitive and Behavioural Assessment (ECAS) score.|Treatment-related changes stratified by disease severity and prognostic indicators.|Peak serum IC14 concentration following administration of the initial dose and peak serum concentration following a course of treatment.|Area under the serum IC14 concentration versus time curve (AUC) following administration of the initial dose and following a course of treatment. | ALS |
| 23 | NCT02058732 | Investigators will study cervical spinal cord chemical concentrations and cervical spinal cord and brain microstructure in amyotrophic lateral sclerosis(ALS) patients who have had a stem cell transplant compared to ALS patients who have not had a stem cell transplant. Investigators intend to determine cervical spinal cord chemical concentrations and cervical spinal cord and brain microstructure in amyotrophic lateral sclerosis(ALS) patients who have had a stem cell transplant and compare these to corresponding measures in amyotrophic lateral sclerosis(ALS) patients who have not had a stem cell transplant. | ALS |
| 24 | NCT01730716 | These stem cells are called Human Spinal Stem Cells (HSSC) and have been engineered from the spinal cord of a single fetus electively aborted after 8 weeks of gestation. The tissue was obtained with the mother's consent. The cells will be transplanted into the ALS patient's spinal cord after laminectomy, an operation that removes bone surrounding the spine. After the spinal cord is exposed, a device manufactured for this purpose will be mounted onto the patient and will hold a syringe filled with the cells. The syringe will have a needle attached and the needle will enter the spinal cord at 5-10 locations injecting the cells. The device will minimize trauma to the spinal cord by the needle by making the puncture precise and steady and injecting the material at a slow and steady speed.||ALS is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is 2-5 years. The cause is unknown and there is no effective treatment. Previous research has shown that on autopsy, ALS patients are found to have increased levels of the amino acid glutamate accumulated in the brain and spinal cord. This increase is thought to be caused by a decrease in the glutamate transporter which normally "cleans up" glutamate from the cells. HSSC are known to express amino acid transporters and it is hoped that this action will reduce the toxicity of accumulated glutamate and benefit ALS patients. There is a second hypothesized benefit of the HSSC and that is their ability to secrete neurotrophic support factors. Neurotrophic factors support the health of nerves.||There will be 5 sequential cohorts (Groups A - E) with 3 subjects in each cohort. New patients will be enrolled into each group. No control group is included. All subjects will receive spinal cord injections of HSSC. All subjects will also be ambulatory with respiratory function greater than or equal to 50% supine and 60% seated of predicted normal and will receive bilateral injections at the C3 through C5 cervical segments. Subjects in Group E will receive bilateral injections at the L2 through L5 lumbar segments and then return approximately one-three months later to receive bilateral injections at the C3 through C5 cervical segments.||The dose escalation plan is as follows:||Group A: 3 ambulatory early-stage subjects with arm weakness but not paralysis, to receive bilateral C3 through C4 injections of 2x106 cells (10 injections x 2x105 cells/ injection)|Group B: 3 ambulatory early-stage subjects with arm weakness but not paralysis, to receive bilateral C3 through C5 injections of 4x106 cells (20 injections x 2x105 cells/ injection)|Group C: 3 ambulatory early-stage subjects with arm weakness but not paralysis, to receive bilateral C3 through C5 injections of 6x106 cells (20 injections x 3x105 cells/ injection)|Group D: 3 ambulatory early-stage subjects with arm weakness but not paralysis, to receive bilateral C3 through C5 injections of 8x106 cells (20 injections x 4x105 cells/ injection)|Group E: 3 ambulatory early-stage subjects with arm weakness but not paralysis, to receive bilateral L2 through L5 injections of 8x106 cells (20 injections of 4x105 cells/ injection) and then approximately 4-12 weeks later to receive bilateral C3 through C5 injections of 8x106 cells (20 injections of 4x105 cells/ injection.||Transition from one group to the next will be determined by review of available safety data by a Safety Monitoring Board (SMB) which will occur approximately one month post surgery of the last subject in the group. The study data will be collected for 6 months post stem cell transplantation of each study subject. However, all subjects will be followed clinically until death and all SAEs and post-study data will be collected and reported. Autopsy will be strongly encouraged for evaluation of pathology and presence of transplanted cells.||The treatment consists of laminectomy or laminoplasty of approximately two to three vertebral segments overlying either L2 through L4 (for Group E only) or C3 through C5 cord segments (for all Groups) in order to allow intraspinal injections of HSSC. Each injection will administer approximately 2, 3, or 4 x 105 cells in approximately 8.5 - 10 µL volume. The subjects will receive 5 or 10 injections at approximately 4 to 5mm intervals on each side of the cord, in total 10 or 20 injections. Each injection is completed in approximately 3 minutes. The total surgical time is expected to be approximately 3 to 5 hours. After the surgery, subjects will receive routine standard of care for laminectomy subjects who undergo an intradural procedure. Prior to and after the transplant, subjects will be required to remain on immunosuppressive therapy. Immunosuppressive therapy will consist of: 1) basiliximab (Simulect®) 20mg intravenously (IV) when the dura is opened, then again at day 4 post transplantation; 2) tacrolimus (Prograf®) initially dosed at a maximum of 0.1 mg/kg divided approximately every 12 hours by mouth (po) on post transplant day 1, and then maintained at a dose that provides a trough serum level of 4 to 8 ng/ml (adjusted for IV use as necessary); and 3) mycophenolate mofetil (CellCept®) started on post transplant day 1 at 500 mg approximately every 12 hours and progressively increased over 2 weeks to 1.0 gram by mouth (po) twice a day as tolerated. Dose escalation may be modified at the discretion of the site Principal Investigator (PI). Subjects will also receive an initial bolus dose of methylprednisolone 125 mg IV approximately 2 hours prior to the first injection. Beginning on post-operative day 1, the subject will receive oral prednisone 60 mg po daily (QD) for 7 days postoperatively, then progressively decreased over the next 21 days as follows: 40 mg/day for 7 days, 20 mg/day for 7 days, then 10 mg/day for 7 days. At 28 days, prednisone will be discontinued. All pre- and post-surgery immunosuppressive drugs will be administered as noted above, at the discretion of the site PI. If these subjects have previously discontinued mycophenolate mofetil and/or tacrolimus, they may be re-challenged as per the dosing described above, at the discretion of the site PI.||The decision to continue immunosuppression therapy will be at the discretion of the site PIs. Mycophenolate mofetil may be dosed down to half or discontinued prior to the end of the study period if the subject experiences adverse reactions to the immunosuppressive agents. If adverse reactions still persist, tacrolimus dose can be further reduced in half and then further considered to be discontinued. Any or all of the immunosuppressive agents may be reduced or stopped at the discretion of the site PI if it is suspected or determined that the immunosuppressive agent is the cause of toxicity and if symptoms of toxicity cannot be managed adequately with symptomatic treatment.||The study will proceed successively from Group A to Group E with a 4-week interval between Groups. The Safety Monitoring Board (SMB) will be convened at the end of the 4-week interval and review all available safety data. Based on the safety outcomes from the 3 subjects in each Group, the SMB will recommend, according to a predetermined rule, whether to enroll 3 new subjects into the next Group, to continue to collect additional information from the same Group, to enroll additional subjects into the same Group, or to suspend the study. Potential subjects will be recruited for the study but put on a waiting list until SMB approval of their treatment. The SMB will consist of 3 neurologists with expertise in ALS, 1 spinal neurosurgeon, 1 neurooncologist, 1 transplant immunologist, and the scientific director of the ALS Association.||Subjects will be assessed for adverse events including pain and infection, motor function, and quality of life. Additional assessments will be made to measure any postoperative changes from baseline in neurologic deficits, imaging studies, bladder or bowel function, allodynia, and neuropathic pain (see schedule of activities). Subjects will also undergo serial assessments of respiratory function (vital capacity (VC) and negative inspiratory force (NIF)), motor function (Ashworth Spasticity Scale, hand-held dynamometry and electrical impedance myography (EIM)), and respiratory function (diaphragm ultrasound). All subjects will undergo cardiac autonomic function testing at Day -14 to Day -2 pre-operatively, and at 1 and 3 months post-operatively to monitor for potential cardiac autonomic neuropathy.||There will be a lead-in period of at least 1 month period of clinical evaluations before surgery to estimate the slope of decline of clinical status. Measures during this lead-in time will be the ALSFRS-R, hand-held dynamometry/grip strength, Ashworth Spasticity Scale, VC and NIF, EIM, and diaphragm ultrasound.Subjects will be followed postoperatively at 2 and 4 weeks, and then at 3, 6, 9, 12, 15, 18, 21, and 24 months, and then at every 6 months thereafter until death. | ALS |
| 25 | NCT03085706 | Amyotrophic lateral sclerosis (ALS) is a rapidly evolving, fatal neurodegenerative disease resulting from the degeneration of cortical, bulbar and spinal motor neurons. The disease progresses inexorably to death, usually because by failure of respiratory function, with a median duration of 3 years.||Recent clinical trials using various types of stem cells, including mesenchymal stromal cells, neural stem cells, and peripheral blood mononuclear cells (PBMCs), represent promising strategies for stem cell-based treatment in ALS. It has been demonstrated that the inflammation and neuronal death were reduced in ALS patients after bone marrow transplantation. In addition, the incidence of immune response was decreased by autologous transplantation of bone marrow cells in ALS patients. PBMCs are multi-potent stem cells that are very attractive for a cell therapy approach in ALS because of their plasticity and ability to provide the host tissue with growth factors or modulate the host immune system. PBMCs were used clinically and few adverse effects were attributed to their administration. Early clinical investigations indicated that the transplantation of autologous PBMCs into the dura is feasible in ALS patients; however, one study was limited to three patients and the other recruited eight patients. There are still many questions regarding the intrathecal transplantation of PBMCs for ALS. Therefore, a retrospective study was performed to assess further the safety and efficacy of the procedure and to test the impact of a cell therapy approach in ALS patients.||Statistical analysis Data, expressed as the mean ± SD, were analyzed using SPSS version 17.0 for Windows (SPSS Inc., Chicago, IL, USA). Statistical analyses were performed by paired sample t-test. A value of P < 0.05 was considered statistically significant. | ALS |
| 26 | NCT02588677 | Masitinib is novel tyrosine kinase inhibitor that targets microglia and mast cells through inhibiting a limited number of kinases. Masitinib blocks microglia proliferation and activation, and mast cell-mediated degranulation, the release of cytotoxic substances that might further damage the motor nerves.||There are two distinct populations of ALS patients: population of "Normal progressors" and population of "Faster progressors". Targeted population for primary analysis is population of "Normal progressors".||"Normal progressors" are ALS patients whose progression of ALSFRS-R score before randomization is less than 1.1 point per month. | ALS |
| 27 | NCT04455542 | Amyotrophic lateral sclerosis (ALS) is a kind of neurodegenerative disease that affects upper and lower motor neurons. In animal model studies have shown that peripheral nerve degeneration in ALS motor function decline, tip peripheral nerve degeneration is of great significance for early progress of ALS may be, at the same time analysis showed that the motor neuron involvement severity and the prognosis of patients with ALS show obvious negative correlation, so finding biomarkers can reflect the motor neuron axonal degeneration is of great significance. Neurofilaments is an intermediate fiber specifically expressed in central and peripheral neurons and can serve as a biomarker for axonal injury, but there is no evidence now that peripheral neurofilament levels have been associated with severity of motor axonal involvement in ALS. | ALS |
| 28 | NCT03081338 | This is a prospective multi-centre observational research project that will be carried out by 8 European partners in 9 sites: 1 in Ireland (Dublin), 1 in the Netherlands (Utrecht), 2 in the United Kingdom (UK) (Sheffield and London), 2 in Italy (Turin and Milan), 2 in Germany (Berlin and Munich), and 1 in Belgium (Leuven). In terms of data collection, the study consists of 3 substudies and will be organised in 6 interlinked work packages spanning clinical, epidemiological and health services research.||All partners will contribute in participant recruitment and collect comparable data, which will be used for fulfilling the deliverables of each work package. Central co-ordination of research activities in the 2 UK sites will be undertaken in Sheffield. This protocol concerns research activities in relation to the ALS-CarE project involving the 2 UK-based participating sites.||Following ethical and research governance approvals, ALS-CarE officially started on 1st April 2014 and will run for 3 years. Participant recruitment will commence following ethical and research governance approval and will occur for the first 4 months at the Sheffield and King's College MND Care Centres. The follow-up period of each participant will take 12 months depending on the rate of progression of the illness. Finally, a period of 11 months at the end of the project will enable analysis of data, dissemination of findings and report writing.||SCIENTIFIC SUMMARY||Background:||Amyotrophic Lateral Sclerosis (ALS) or else known as Motor Neurone Disease (MND) is a progressive neurodegenerative disease that strikes in the prime of life. There are currently no effective disease modifying therapies for ALS and death usually occurs within 3 years of symptom onset. Management is palliative and is aimed at maximising quality of life and minimising the burden of disease. The complexity and rapidly progressive nature of ALS requires a responsive multidisciplinary care system that that is built on reliable disease staging and evidence based symptom management.||Aim:||To incorporate detailed clinical information drawn from population based sources into a responsive care programme.||Plan of investigation:||A standardised staging system will be validated, and quality of life and patient experiences will be measured and management optimised across disease stages from diagnosis to end of life. Health economic analysis will identify key differences in resource utilisation and will be useful for pharmaco-economic analyses of new therapeutics.||Potential impact:||The completed project will provide a user-friendly best practice framework for ALS that can be modified for management of other neurodegenerative diseases. | ALS |
| 29 | NCT02881476 | Amyotrophic lateral sclerosis (ALS) is one of the progressive neurodegenerative disorders, affecting upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Hence, the signs of damage motor neurons are both at the peripheral (eg. atrophy), and central (eg. spasticity) level. There is no effective treatment for ALS and the majority of patients die within 5 years after diagnosis, usually due to the respiratory failure. Numerous studies on murine models revealed that mesenchymal stem cells (MSCs) successfully improve the clinical and pathological features of ALS patients. The goal of this nonrandomized, open label study is to investigate the safety and tolerability of allogeneic Wharton's jelly-derived mesenchymal stem cell transplantation into the individuals with diagnosed amyotrophic lateral sclerosis. This clinical trial is conducted to test the therapeutic (neuroprotective and paracrine) effect of allogeneic Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs). All patients enrolled will have a documented history of ALS disease prior to enrollment. Patients are recruited for a clinical trial no more than 1 year from the disease diagnosis. Then, patients are divided into two groups: Group I - patients receiving intrathecally one application of WJ-MSCs and Group II - patients receiving intrathecally three applications (each administration every two months) of WJ-MSCs. Subsequently, allogeneic Wharton's jelly-derived mesenchymal stem cell transplantation to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC) and functional rating scale (FRS) to establish ALS progression rate will be recorded throughout the duration and in the post-treatment follow up period. | ALS |
| 30 | NCT04326283 | Trametinib (SNR1611) is a MEK inhibitor that downregulates the MAPK/ERK pathway. In this study, the potential of MAPK/ERK pathway downregulation through trametinib (SNR1611) as a therapeutic treatment for amyotrophic lateral sclerosis (ALS) will be evaluated. | ALS |
| 31 | NCT03103815 | Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting upper and lower motor neurons. Survival is typically 2 to 5 years from symptom onset; death is usually from respiratory paralysis. Standard therapy is with Riluzole 100 mg/day, a FDA approved treatment for ALS that has a small effect on survival. There is a strong need for more effective therapies in ALS.||In our previous studies, we have shown that Amivita, a compound of amino acids and vitamines, is effective for neuronal injury (unpublished data). We have since then use this regimen to treat ALS patients. Our retrospective analysis (unpublished data) of the treated patient indicates that this regimen can slow down the progression of ALS.||We proposed a self-controlled clinical trial to study the safety and efficacy of Amivita. Secondary outcome measures include weight and quality of life. Twenty subjects in our ALS center who are already receiving riluzole will receive treatment for 12 months. The evaluating investigators will be blinded to treatment assignment. Primary outcome measures will be adverse events, the ALS Functional Rating Scale-Revised (ALSFRS-R), and survival. Secondary outcome measures include body weight, forced vital capacity (FVC), quality of life and grip strength.||The total study length from first enrolled subject will be approximately 6 months.||Participants in this study will be subjects with familial or sporadic ALS diagnosed as probable, or definite, according to the World Federation of Neurology El Escorial criteria. Diagnostic and Inclusionary/Exclusionary criteria will be clearly outlined in the protocol. | ALS |
| 32 | NCT02881489 | Amyotrophic lateral sclerosis (ALS) is one of the progressive neurodegenerative disorders, affecting upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Hence, the signs of damage motor neurons are both at the peripheral (eg. atrophy), and central (eg. spasticity) level. There is no effective treatment for ALS and the majority of patients die within 5 years after diagnosis, usually due to respiratory failure. Numerous studies on murine models revealed that mesenchymal stem cells (MSCs) successfully improve the clinical and pathological features of ALS. The goal of this nonrandomized, open label study is to investigate the safety and tolerability of autologous bone marrow-derived mesenchymal stem cell transplantation into the individuals with diagnosed amyotrophic lateral sclerosis. This clinical trial is conducted to test the therapeutic (neuroprotective and paracrine) effect of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients are recruited for a clinical trial not longer than 1 year from disease diagnosis. Then, patients are divided into two groups: Group I - patients receiving intrathecally one application of BM-MSCs and Group II - patients receiving intrathecally three applications (each administration every two months) of BM-MSCs. Subsequently, autologous bone marrow-derived mesenchymal stem cell transplantation to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC) and functional rating scale (FRS) to establish ALS progression rate will be recorded throughout the duration and in the post-treatment follow up period. | ALS |
| 33 | NCT02710162 | This research study is being performed to determine how accurate different screening tools or tests are at identifying swallowing problems associated with Amyotrophic Lateral Sclerosis (ALS).||As a participant one evaluation will be performed at the University of Florida Swallowing Systems Core laboratory located at Shands Hospital, Gainesville will take place. This will take approximately two-hours. During this evaluation an videofluoroscopy (X-ray of swallowing), cough tests, tongue function test and questionnaires will be completed. | ALS |
| 34 | NCT03073239 | The objective of this research is to pursue potentially involved genetic mutations in this disease (new or previously described), in addition to carry out a epidemiological questionnaire including data on personal history, environmental and occupational exposure that might be underlying this high prevalence. | ALS |
| 35 | NCT03892863 | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of central and peripheral motor neurons. ALS leads to death usually within 3 to 5 years from the onset of the symptoms. Available treatment can prolong the disease duration but cannot modify the disease course. Depression is a frequent complication of ALS, which further decreases quality of life and the available data concerning effectivity of antidepressant drugs are conflicting. Similarly, the apathy may also complicate ALS and worsen the prognosis. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with proved antidepressive effect in patients suffering from major depression and in depression associated with several neurological disorders such as Parkinson's disease or stroke.||The purpose of this study is to compare the effectiveness rTMS in improving the depression and - as a secondary outcome - the apathy and daily functioning in patients with ALS.||Intervention will include ten daily sessions of rTMS. In each session 3000 magnetic pulses will be administered over the left dorsolateral prefrontal cortex. Stimulation intensity will equal 120% of the motor threshold value for the right first dorsal interosseus.||Assessment of depression severity and of apathy and daily functioning will be made before and after therapy, as well as two and four weeks later. | ALS |
| 36 | NCT00353665 | Phase 2/3 trial in ALS patients Double-blinded, parallel, randomized (2 blocs, bulbar/spinal onset)||Memantine + riluzole x Placebo + Memantine||Inclusion criteria:||< 75 years at disease onset|< 3 years of disease progression|ALS-FRS > 24|FVC > 60|Probable or definite disease (revised El Escorial criteria)|No other medical condition|Normal blood tests|Regular medication on riluzole > 1 month|Nerve conduction studies ruling out conduction block|EMG with widespread loss of motor units (revised El Escorial criteria)|At least one hand with ADM strength > 2 on MRC scale||Duration - 2 years||Evaluation - every 3 months||Primary outcome - ALS-FRS Secondary -SF36, Hamilton depression scale, motor unit number estimation, neurophysiological index, strength (clinical evaluation); side-effects||Intention to treat analysis||60 patients||number estimated for 50% change in decline rate of ALS-FRS | ALS |
| 37 | NCT01348451 | These stem cells are called Human Spinal Stem Cells (HSSC) and have been engineered from the spinal cord of a single fetus electively aborted after 8 weeks of gestation. The tissue was obtained with the mother's consent. The cells will be transplanted into the ALS patient's spinal cord after laminectomy, an operation that removes bone surrounding the spine. After the spinal cord is exposed, a device manufactured for this purpose will be mounted onto the patient and will hold a syringe filled with the cells. The syringe will have a needle attached and the needle will enter the spinal cord in specified areas. The device will minimize trauma to the spinal cord by the needle by making the puncture precise and steady and injecting the material at a slow and steady speed.||ALS is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is 2-5 years. The cause is unknown and there is no effective treatment. Previous research has shown that on autopsy, ALS patients are found to have increased levels of the amino acid glutamate accumulated in the brain and spinal cord. This increase is thought to be caused by a decrease in the glutamate transporter which normally "cleans up" glutamate from the cells.||Because the HSSC are human in origin, their transplantation will be handled in some ways like other organ transplants in that patients will receive immunosuppressive medications to prevent the rejection of the cells. Right before and immediately after surgery patients will receive infusions of a drug called basiliximab. After surgery they will take prednisone and be tapered off that medication over one month. They will also be given two other immunosuppressive agents, tacrolimus and mycophenolate mofetil after surgery and it is expected that the patients will take these drugs for the rest of their lives. | ALS |
| 38 | NCT03272503 | Amyotrophic lateral sclerosis (ALS) or Lou Gehrig's disease is a neuromuscular disease that results in rapid decline in normal muscle function and tone leading to difficulties with mobility, eating, drinking, breathing, sleeping, and communicating. The disease is progressive and no cure currently exists. Most people diagnosed with ALS succumb within 3 to 5 years. Rilutek® (riluzole) has been approved as a treatment to slow progression of ALS, but is minimally effective with mean increase in survival of only a few months. Radicava® or Radicut® (edaravone) has recently been approved in Canada, USA, Japan and South Korea.||Muscular dysfunction present in people with ALS is caused by nerve breakdown and a dysfunction in the communication between the muscles and the nerves. The area where these communications occur is called the neuromuscular junction. Some recent studies have focused on using different medications to enhance communication at the neuromuscular junction with the goal of improving muscle function as a result. This approach is unproven but may help to slow the progression of the disease.||Pimozide is a medication that has been demonstrated to enhance communication at the neuromuscular junction in fish and mice. This study will look at whether Pimozide may help to slow the progression of ALS.||There are two parts to this study.||Treatment Phase: In the first part of this study, 100 people from several Canadian centres with ALS who have provided their consent will be randomly assigned into one of 2 groups. The first group will receive a dose of up to 2mg of Pimozide per day and the second group will receive placebo (lactose tablets). Subjects will be assigned randomly (like by a flip of a coin) to receive either Pimozide 2 mg per day or placebo tablets. There will be a fifty-fifty chance of receiving Pimozide or placebo.||Each Pimozide tablet contains 2 mg of Pimozide. The matching placebo tablets for this study will look exactly like the Pimozide tablets. Placebos are used in clinical trials to find out if the results observed in the study are due the drug being tested, or for other reasons.||Neither the subject nor their doctor will know which group a patient belongs to. However, if an emergency should arise, information about a treatment group will be shared with their doctor to ensure appropriate medical care. Participants will take their treatment once a day, every day for about 22 weeks. The total time in the study from the screen visit up until the last phone call communication is about 26 weeks.||Observational Phase: The second part of this study is optional. It is each subject's decision whether to participate only in the first part of this study, or in both parts of the study, or not at all. In the second part of this study, the Canadian Neuromuscular Disease Registry (CNDR) will collect data on overall ALS progression using the Revised ALS Functional Rating Scale (ALSFRS-R) and breathing using Vital Capacity data collected during breathing tests. This information will be collected from a subject medical record following each routine clinical appointment. Data will be collected at each routine clinic visit for up to 5 years from the end of the first part of the study. There will be no extra visits for this part of the study beyond routine ALS clinic visits.||The information collected during this part of the study will be used to compare the progression of ALS, after the clinical trial is completed, among the two treatment types (Placebo or 2 mg per day). By analyzing this information, the researchers conducting this study hope to determine if Pimozide may help to slow the progression of ALS. To participate in this part of the study consent must be provided to join the CNDR. A subject who hasn't already provided their CNDR consent, and wishes to participate in this part of the study will be given a CNDR consent form to review and sign in addition to this consent form. A subject already participating in the CNDR will just need to sign the main study consent form. | ALS |
| 39 | NCT02383654 | This pilot clinical trial is design to see the safety and possible efficiency of ADSCs treatment in a ALS patient. one subjects will be treated (n=1). The patient will receive brain transplantation of ADSCs and combines intravenous infusion ADSCs 4 times. Subjects will be assessed by adverse effects and functional outcomes of clinical: PI max , PE max,and Haloscale respiration, ALS functional rating scale (ALS-FRS) are analyzed at 1 month, 3 months, 6 months 9 months and 12 months.||Brain MRI scans will be obtained before and after the treatment. Long term follow-up will be performed at 1, 6 , and 12months for safety reasons. Brain CT for check operation safety before and after brain implantation.||Timing of Study: 12months recruitment period after approvals | ALS |
| 40 | NCT00877604 | Amyotrophic lateral sclerosis (ALS), or motor neuron disease (MND), is a rapidly progressive, fatal neurodegenerative condition characterized by loss of upper and lower motor neurons in the brain and spinal cord. The terms ALS and MND are often used inter-changeably to cover the different clinical syndromes, which include upper and lower motor neuron disorder, progressive bulbar palsy, and pseudo-polyneuritic form.||Degeneration of lower motor neurons (LMN) in the anterior horns of spinal cord and brainstem leads to progressive muscular atrophy and eventually to death within a few years due to respiratory insufficiency. During the course of the disease, the involvement of tongue and pharynx muscles causes swallowing impairment with marked drooling, need of parenteral or enteral feeding, and finally gastrostomy. Denervation of laryngeal muscles causes loss of speech. Cramps and fasciculation typically occur from the early phases of the disease. Degeneration of upper motor neurons (UMN) in the brain cortex causes pyramidal tract dysfunctions including clonus, Babinski sign, hypertonia, and loss of dexterity that further limit patients' daily activities.||The incidence of ALS varies from 0.2 to 2.5 cases per 100,000 per year, although estimates vary between countries, likely reflecting a combination of availability of medical services, diagnostic accuracy, and demo-graphic characteristics of the area. Increasing life expectancy and improvements in standards of treatment and care will also result in an increased incidence of ALS. Globally, the overall rate is approximately 2 per 100,000. Its prevalence is approximately of 7 per 100,000. In Italy, the reported incidence of ALS is 2.2 cases/100,000/year.||There is currently no cure for ALS. Despite initial positive results in preclinical and early clinical studies, large-scale clinical trials with all agents except riluzole failed to demonstrate a clinically meaningful therapeutic effect in patients with ALS. Riluzole at the dose of 100 mg/day showed a significant difference on survival (6.4%; gain of 3 months) and slowed deterioration in muscle strength.||Primary involvement of apoptotic mechanisms has important implications in selecting drug candidates for therapy in ALS. Recent preclinical studies have demonstrated that TUCA is endowed with antioxidant, antiapoptotic and neuroprotective activities. In particular, TUDCA can cross the blood-brain-barrier and has been shown to exert a significant therapeutic effect in a model of HD mice.||Tauroursodeoxycholic acid (TUDCA) is a hydrophilic bile acid that is normally produced endogenously in humans at very low levels. TUDCA is synthesized in the liver by conjugation of taurine to ursodeoxycholic acid (UDCA), which is commonly used as a bile acid replacement therapy for the treatment of certain cholestatic syndromes.||The main pharmacological activity of TUDCA consists in its ability in increasing the cholesterol solubilising activity of bile, thus transforming "lithogenic" bile in "non-lithogenic" or "litholytic" bile.||TUDCA inhibits mitochondrial-associated apoptosis via many pathways: 1) it inhibits the mitochondrial permeability transition (MPT) and cytochrome C release, 2) it inhibits mitochondrial membrane depolarization, and 3) it antagonizes Bax translocation from the mitochondria and caspase activation in hepatocytes and brain. TUDCA may also ease oxidative stress.Study relevant TUDCA pharmacology consists in its antioxidant, antiapoptotic and neuroprotective activities evidenced in preclinical studies.||Recent reports have shown that hydrophilic bile acids, such as UDCA and TUDCA, can prevent hepatic cytotoxicity through several mechanisms. For example, TUDCA prevents the production of reactive oxygen species and thus acts as an antioxidant. Additionally, TUDCA mitigates mitochondrial insufficiency and toxicity, and prevents apoptosis, in part, by inhibiting Bax translocation from cytosol to the mitochondria. In hepatocytes, this inhibition results in reduced mitochondrial membrane perturbation, release of cytochrome c, and activation of downstream caspases. TUDCA reduced cytotoxicity in neurons through similar mechanisms, as well as mitochondrial pathways that are independent of the permeability transition. TUDCA prevented striatal degeneration and ameliorated locomotor and cognitive deficits in the in vivo 3-nitropropionic acid (3-NP) rat model of HD. Intracellular inclusions were significantly reduced, and the TUDCA-treated mice showed improved locomotor and sensorimotor abilities.||In addition, the antiapoptotic and cytoprotective effects of TUDCA have been tested in models of acute stroke. The possibility that TUDCA exerts an antiapoptotic action by ameliorating mitochondrial function raises the issue whether other neurological disorders, including Friedreich's ataxia, amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease, can benefit by the administration of TUDCA. This drug is a candidate neuroprotective agent for a variety of chronic neurodegenerative conditions. | ALS |
| 41 | NCT02000713 | Currently there is no definitive diagnostic test for amyotrophic lateral sclerosis (ALS). The investigators' goal is to determine if magnetic resonance imaging can provide an accurate diagnosis of ALS by looking at chemical concentrations in the spinal cord at the neck level which show up in MRI imaging and compare these chemical concentrations to corresponding measures in healthy control subjects. | ALS |
| 42 | NCT03828123 | Subjects will be assigned to autologous mesenchymal stromal cell (AMSC) treatment according to inclusion and exclusion criteria (see below) screened four times prior to administration. Then the subjects will be observed for three consecutive yearsAfter a half year of screening period, the autologous multipotent mesenchymal stromal cells from bone marrow will be isolated. The cells will be cultivated for 3 passages (3 - 4 weeks) in order to get sufficient amount for therapy, cell suspension for intrathecal application will be prepared and introduced intrathecally through lumbar puncture. Subsequently, all the subjects will be observed at the range of standard medical care used at these types of interventions. | ALS |
| 43 | NCT01823380 | Amyotrophic lateral sclerosis is one of the most serious neurodegenerative disease, leading to death in 3 years by progressive paralysis of 4 limbs, speech, swallowing and breathing, and due to a progressive death of central and peripheral neurons. The cause of the disease is unknown, but an immunologically factor is more precisely suspected in ALS. Since 2008, the work of Immunology have shown that vitamin D was a major regulator of immunity. It regulates particularly the function of dendritic cells and regulates the immune response in macrophages. A vitamin D deficiency will induce activation of microglia. In neurology, vitamin D deficiency is associated with a greater impairment in neuronal function. This deficit is associated with a faster alteration of the microvasculature, alteration known to increase neuronal suffering and to enhance the neurodegenerative processes. The investigators postulate that ALS patients have a more severe prognosis if their vitamin D levels at the time of diagnosis is lower. The main objective of this study is to investigate the correlation between the rate of motor decline and blood levels of Vitamin D total. Secondary objectives are to investigate the relationship between blood levels of vitamin D and total disease duration of ALS, forced vital capacity, weight loss, age of onset and the start site of ALS. | ALS |
| 44 | NCT00231140 | Study drug will be provided as 50 mg tablets. Patients will be instructed to take 2 tablets orally once a day during the evening at least 60 minutes after a meal. Thalidomide will be administered starting at 100 mg (Group 1) for 6 weeks. Thereafter, the dose will be increased every week by 50mg until reaching the dose of 400 mg/day. This treatment is continued for 12 weeks. Thalidomide is administered in conjunction with the standard treatment of riluzole (100mg/day). | ALS |
| 45 | NCT00958048 | Objectives: Amyotrophic lateral sclerosis is the commonest motor neuron disease with incidence of 0.8 person-years in Chinese. Respiratory muscle function has been proposed to be a strong predictor of quality of life (QoL) and survival in ALS. Some studies suggest that most patients with ALS developed hypoventilation when their vital capacity (FVC) is less than 50% of predicted value. However, the incidence of hypoventilation and factors associated with hypoventilation in ALS patients is not clear. Also, there is still no consensus as to which physiologic marker should be used as a trigger for the initiation of non-invasive ventilation (NIV) in ALS patients. The conflicts of studies come from variable subgroup of ALS, pulmonary function at enrollment, techniques used to diagnose ALS, time to apply NIV, and target endpoint. Therefore, this project aimed to study ALS patients who had relatively preserved respiratory muscle function and no respiratory failure at clinical to achieve three goals: (1) To determine the incidence of hypoventilation in ALS patients (2) To identify the clinical characteristics and risk factors associated with hypoventilation in ALS patients (3) To determine the effect of early intervention with NIV on the prognosis of ALS patients Study design: Randomized, controlled trial Participants: ALS patients whose FVC 40%-80% of predict, Pimax <60mmHg, and daytime PaCO2<50mmHg Protocol: Eligible patients with whole-night polysomnography (PSG) and transcutaneous CO2 (PtcCO2). Enrolled patients were randomized to standard treatment or NIV. The primary endpoint of prognosis was survival. The secondary endpoint was changes of PtcCO2 and PaCO2, unexpected admission or clinic visiting, daytime function and QoL.||Statistic: The baseline demographics of patients with or without hypoventilation were compared to determine the factors associated with hypoventilation in ALS patients. The impact of NIV in ALS patients was determined by comparing the primary and secondary goals between standard treatment and NIV group. A two-sided p value of < 0.05 was considered statistically significant.||Clinical implication: Hypoventilation at ALS patients who had relatively preserved respiratory muscle function and no respiratory failure at clinical sleep was common, early identification through PSG screening and PtcCO2 will allow for the early diagnosis and intervention. Understanding the time of applying NIV and the effect on prognosis in ALS will allow for the early intervention and prediction of outcomes. | ALS |
| 46 | NCT02969759 | The investigators will study fibroblasts derived from sporadic ALS patients.||Clinical parameters will be collected such as sex, age, age of onset, clinical presentation, electrophysiological an respiratory parameters, treatments.||Patients and controls derived fibroblasts will be amplified and cultivated from skin biopsies.||Primary fibroblast cell cultures will be derived from skin biopsies obtained from control subjects and from the patients after obtaining written consent. Amplifications will be performed, from passage 1 to 6, allowing the time for cell cryopreservation of 10 samples per cell line. All experiments will be conducted on cells with similar passage numbers, ranging from 6 to 25, to avoid artefacts due to senescence.||Cell growth of each line will be monitored with the IncuCyte ZOOM® system (Essen Biosciences), a microscope gantry that resides in a cell incubator, and a networked external controller hard drive that gathers and processes image data. Cell growth will be automatically calculated at each time point using the relative cell density (ratio of the occupied area to the total area of the acquired regions).||The respiratory parameters of the fibroblasts will be monitored precisely with an high resolution oxygraph (OROBOROS). Enzymatic activity of each complex of the mitochondrial respiratory chain will be measured by spectrometry, and the mitochondrial membrane potential will be studied with fluorescence microscopy (TMRM probe). The investigators will also study mitochondrial dynamics and the architecture of mitochondrial network with fluorescence microscopy and super-resolution microscopy (SRM, Roper). The production of free radicals will be estimated with probes sensitive to oxidative stress. Finally, a metabolomic study (mass spectrometry QTRAP LC/MS/MS 5500 ABSciex) will be performed to characterise precisely the metabolites in the cells and to assess their metabolic profile.||The investigators will search for protein inclusions (intermediate filaments, TDP43, FUS, ubiquitin) with immuno-fluorescence technics. Western Blots will be performed to study the protein metabolism. The architecture of the cytoskeleton will be analysed in SRM and fluorescence microscopy, and the investigators will try to transfect fibroblasts in order to express Neurofilaments and study the consequences on the cytoskeleton and protein metabolism.||The investigators will study the response of the cells to the stress (hypoxia SCI-tive Dual, starvation), and to senescence (high passage numbers). | ALS |
| 47 | NCT00790582 | This is a Phase II Screening study. There is no placebo (inactive or 'fake' drug) in this study, meaning that all participants will be taking lithium carbonate. The purpose of this study is to find out if lithium carbonate is safe to be used in people with ALS and if it can slow the progression of the disease.||A recent article was published in a highly regarded medical journal that showed a positive effect of lithium carbonate on an ALS type mouse. The researchers then studied a very small number of people with ALS, giving 16 people lithium carbonate with riluzole and giving 28 people only riluzole. The people who took lithium remained stronger for a considerably longer period of time. However, the study was very small and we cannot really tell if lithium works unless a larger study is performed. It is not well understood why lithium carbonate might be helpful but it is believed that it may play a role in protecting the motor nerves from the damage of ALS.||If you choose to participate, you will need to go to your study clinic for research study visits 7 times in one year and you will have 4 telephone interviews during that time. These visits and phone calls could take up to 17 hours in total.||Caution: Lithium is an FDA approved drug used for some psychiatric disorders. It is not FDA approved for ALS. Lithium has many potentially serious side effects and must only be taken under close supervision of your physician. | ALS |
| 48 | NCT02437110 | Objective:||In this Phase I, proof-of-concept study, we aim to determine whether an antiretroviral regimen approved to treat human immunodeficiency virus (HIV) infection would also suppress levels of Human Endogenous Retrovirus-K (HERV-K) found to be activated in a subset of patients with amyotrophic lateral sclerosis (ALS). We propose to measure the of blood levels of HERV-K by quantitative PCR before, during, and after treatment with an antiretroviral regimen. We will evaluate the safety of the antiretroviral regimen for participants with ALS and also explore clinical and neurophysiological outcomes of ALS symptoms, quality of life, and pulmonary function.||Study Population:||We will study a subset of ALS patients who have a ratio of HERV-K:RPP30 greater than or equal to 13. About 30% of ALS patients may have detectable levels of HERV-K; about 20% of patients with ALS have a level >1000 copies/ml. To show whether the HERV-K could be suppressed, we will recruit from the approximately 20% of patients with the high levels so that the antiretroviral effect can be determined.||Design:||This is an open-label study of a combination antiretroviral therapy for 24 weeks in 20 HIV-negative, HTLV-negative ALS patients with high ratio of HERV-K:RPP30. The study duration for each participant will be up to 60 weeks. Participants will be followed regularly for safety, clinical, and neurophysiological outcomes.||Outcome Measures:||The primary outcome measure will be the percent decline HERV-K concentration measured by quantitataive PCR. Percent decline for a patient is measured by: 100 x (screening visit - week 24 visit measurement) / screening visit. The safety of antiretrovirals in volunteers with ALS as measured by the frequency and type of AEs, the ability to remain on assigned treatment (tolerability), physical examinations, laboratory test results, vital signs, and weight/body mass index (BMI). Efficacy will be explored by measuring the change in mean scores of: the ALS Functional Rating Scale-Revised (ALSFRS-R), the ALS Specific Quality of Life Inventory-Revised (ALSSQOL-R), the ALS Cognitive Behavioral Screen (ALS-CBS), vital capacity and maximal inspiratory pressure as measured by handheld spirometer, electrical impedance myography (EIM), the change in neurofilament levels in blood and/or CSF, and the change in uring p75ECD levels. | ALS |
| 49 | NCT01650818 | Scarce evidence is available regarding aerobic exercise training of patients with ALS. Some studies using transgenic mouse models of familial ALS have shown markedly slowed disease progression, improved functional capacity, and extension of survival in animals undergoing aerobic exercise training. In humans, only one non-randomized study has shown that moderate-intensity aerobic exercise training was of little beneficial effect in a small group of patients with Kennedy disease, a rare X-linked progressive neuromuscular disease involving lower motorneurons, presenting a pathophysiological picture quite different from that of ALS. To the best of our knowledge, the safety and the effects of aerobic exercise training on functional capacity and quality of life of patients with ALS have not been systematically evaluated as yet in a randomized, controlled trial with an adequate sample size. | ALS |
| 50 | NCT00800501 | Vascular endothelial growth factor (VEGF) is an endogenous human protein fundamental to the development of the vascular and nervous systems in the body. A role for VEGF in ALS has been suggested from observations in animal models of the disease as well as observations of a dysregulation of VEGF production in patients with ALS.||NeuroNova intends to investigate whether intracerebroventricular administration of VEGF165 in the form of the drug product sNN029 can improve motor function and prolong survival in patients with ALS, and in this first study the safety and tolerability of treatment for 3 months will be evaluated.||Assessments will include:||Electrocardiograms, vital signs and clinical laboratory tests|Adverse events and withdrawals related to adverse events|Possible pathological changes in the brain, spinal cord or retina identified through magnetic resonance imaging and funduscopy|Possible signs of intracranial bleeding or loss of blood-brain-barrier integrity through measurements of bilirubin and albumin levels in cerebrospinal fluid collected through lumbar and cervical puncture|Device performance as characterized by catheter tip placement (determined by imaging) and infusion accuracy (pump residual volume)||The secondary objective of this study is:||To explore the effect of ICV administration of sNN0029 on the time course of Amyotrophic Lateral Sclerosis related parameters including:||Disease activity as measured by Amyotrophic Lateral Sclerosis Functional Rating Scale|Quality of life as measured by the EQ-5D rating scale|To explore the levels of VEGF165 in cerebrospinal fluid collected through lumbar and cervical puncture. | ALS |
| 51 | NCT03367650 | The amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis due to degeneration of motor neurons in the primary motor cortex, corticospinal pathway, brain stem and spinal cord. The incidence is estimated at 2/100 000 per year and prevalence at approximately 4/100000.||Various clinical forms are described. The disease is fatal is 3-5 years on average.||The majority of cases are sporadic and of unknown origin but 5-10% are familial and present for 20% of them, mutations in the SOD1 (21q22.11) gene. Other genes have recently been implicated in ALS. Environmental toxic factors have been extensively researched. Beta-methylamino-L-alanine (BMAA), a neurotoxic nonprotein amino acid produced by most cyanobacteria, has been proposed to be the causative agent of the ALS-Parkinsonism Complex on the island of Guam in the Pacific Ocean.||Epidemiology and clinical features of ALS have never been studied in Caribbean countries.||The main purpose of the study will be to evaluate the incidence of ALS in Guadeloupe and Martinique.||Secondary purposes will be:||to evaluate the presence of specific phenotypic features;|to establish he prognosis of different clinical forms;|to study the genes implicated in ALS and quantify theexposure to BMAA.||Since 2000, the diagnosis of ALS is made in about 20 patients per year in Guadeloupe and Martinique(for a total population of 800000 inhabitants) but the incidence and the clinical presentation of ALS in the French West Indiesare unknown.||The exceptional association of ALS and parkinsonism is regularly observed in Guadeloupe. We propose to perform a prospective descriptive and longitudinal epidemiological study to determine the incidence of ALSin the French West Indies. In parallel we will study the involvement of genetic andenvironmental toxic factors as etiological factor for this disease.||Primary outcome:||- the impact of ALS in Guadeloupe and Martinique||Secondary outcomes:||Assess the clinical characteristics (presence of phenotypic features?),|the prognosis of different clinical forms study,|to establish the genetic factors of the ALS and to search potential environmental factors | ALS |
| 52 | NCT04514952 | Once the eligibility is confirmed, approximately 1-2 weeks after the screening visit, the subject will return for the baseline/first infusion visit. Subsequent treatments will occur 2 weeks apart for 18 weeks, for a total of 10 infusions. Follow-up visits will occur at 22 weeks, 26 weeks and 39 weeks. End of study visit will occur at 52 weeks.||Baseline/Infusion 1 Visit||A verification of patient consent will be verbally performed and included in the progress note.|Review of medical history, and concomitant medications.|Physical exam + ALS Functional Rating Scale-Revised (ALSFRS-R)|Vital signs (Heart Rate, Blood Pressure, Respirations, Temp., SpO2)|Weight measurement||Blood samples will be collected for safety and efficacy assessments:||Hematology|Chemistry|Coagulation Panel|Proinflammatory Cytokines (IL-2, IL-6, TNF-a)|C- Reactive Protein (CRP)||The HB-adMSCs will be administered and the patient closely observed:||• One intravenous infusion of HB-adMSCs (2x108 cells) to last 1 hour:||Volume: 250 ml of Saline Solution 0.9%.|Rate: 83gts/min (250ml/h)||The subject will then be monitored for a minimum of 2hr after infusion as follows:||Measure Vital signs at minute 0 of infusion.|Measure Vital signs at minute 15 after IV infusion.|Measure Vital Signs at minute 30 after IV infusion.|Measure Vital signs at minute 60 after IV infusion.|Measure Vital signs at minute 120 after IV infusion. (Vital signs will be recorded more frequently if clinically indicated).|Adverse event monitoring|24 hrs. Telephone encounter. The subject will be contacted by telephone the following day after the infusion visit to determine if any adverse events have occurred.|ALS-specific Quality of Life Survey-revised (ALSSQOL-R)|A video recording will be made with the purpose to capture patient's overall status (gait, range of motion assessments, etc.).||One week following infusion, PI will perform an assessment to determine patient status and discuss any changes since previous infusion.||Infusion Visits Week 2,6,10,14 and 18||Review and update medical history|Update concomitant medications list|Weight measurement|Vital signs (Heart Rate, Blood Pressure, Respirations, Temp., SpO2)|Physical examination + ALS Functional Rating Scale-Revised (ALSFRS-R)||The HB-adMSCs will be administered and the patient closely observed:||• One intravenous infusion of HB-adMSCs (2x108 cells) to last 1 hour:||Volume: 250 ml of Saline Solution 0.9%.|Rate: 83gts/min (250ml/h)|Adverse event monitoring|24 hrs. Telephone encounter. The subject will be contacted by telephone the following day after the infusion visit to determine if any adverse events have occurred.||Infusion Visits Week 4, 8, 12, and 16||Review and update medical history|Update concomitant medications list|Weight measurement|Vital signs (Heart Rate, Blood Pressure, Respirations, Temp., SpO2)|Physical examination and ALS Functional Rating Scale-Revised (ALSFRS-R)||Blood samples will be collected for safety and efficacy assessments:||Hematology|Chemistry|Coagulation Panel|Proinflammatory Cytokines (IL-2, IL-6, TNF-a)|C - Reactive Protein||The HB-adMSCs will be administered and the patient closely observed:||• One intravenous infusion of HB-adMSCs (2x108 cells) to last 1 hour:||Volume: 250 ml of Saline Solution 0.9%.|Rate: 83gts/min (250ml/h)|ALS-specific Quality of Life Survey-revised (ALSSQOL-R)|Adverse event monitoring|24 hrs. Telephone encounter. The subject will be contacted by telephone the following day after the infusion visit to determine if any adverse events have occurred.||Follow-Up Visit Week 22||You will be asked about your current health and medical history (if any changes since last study visit or telephone call).|You will be asked if there was any change in the medication list you have previously provided (Concomitant medication list).|Your blood pressure, heart rate, respiration rate, temperature, oxygen saturation and weight will be measured.|The doctor will perform a physical examination driven by the signs and/or symptoms you experience, if any.|The doctor will perform tests including the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure the symptoms of ALS Disease on how you are able to perform.|You will be asked to complete the Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) questionnaire to assess the impact of Amyotrophic Lateral Sclerosis on your quality of life.|You will be reminded to stay on your stable regimen of treatment throughout the study||Follow-Up Visit Week 26||You will be asked about your current health and medical history.|You will be asked about the medicines that you have taken and are currently taking for Amyotrophic Lateral Sclerosis and for other health issues.|Your blood pressure, heart rate, respiration rate, oxygen saturation, temperature, and weight will be measured.|The doctor will perform a complete physical examination.|The doctor will perform tests including the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure the symptoms of ALS Disease on how you are able to perform.|You will be asked to complete the Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) questionnaire to assess the impact of Amyotrophic Lateral Sclerosis on your quality of life.|Laboratory test will be done. About 6 tablespoons of blood will be taken from your arm using a needle. Your blood will be tested to measure your overall health and efficacy markers (TNF-a, IL-6, IL-2 and C - Reactive Protein).|You will be given an order for a Chest X ray (PA single view) and Magnetic Resonance Imaging to be performed. If within 7 days of the End of study visit you have undergone any or both, such reports would suffice this requirement.|An Electrocardiogram (ECG) will be performed to evaluate cardiac function.|An Electromyogram (EMG) will be performed to evaluate neuromuscular function.|A video documenting of yourself walking and sitting will be performed.||Follow-Up Visit Week 39||You will be asked about your current health and medical history (if any changes since last study visit or telephone call).|You will be asked if there was any change in the medication list you have previously provided (Concomitant medication list).|Your blood pressure, heart rate, respiration rate, temperature, oxygen saturation and weight will be measured.|The doctor will perform a physical examination driven by the signs and/or symptoms you experience, if any.|Laboratory test will be done. About 6 tablespoons of blood will be taken from your arm using a needle. Your blood will be tested to measure your overall health and efficacy markers (TNF-a, IL-6, IL-2 and C - Reactive Protein).|The doctor will perform tests including the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) to measure the symptoms of ALS Disease on how you are able to perform.|You will be asked to complete the Amyotrophic Lateral Sclerosis-Specific Quality of Life-Revised (ALSSQOL-R) questionnaire to assess the impact of Amyotrophic Lateral Sclerosis on your quality of life.|You will be reminded to stay on your stable regimen of treatment throughout the study||End of Study Visit Week 52||Review and update medical history|Review and update concomitant medications list|Weight measurement|Vital signs (Heart Rate, Blood Pressure, Respirations, Temp., SpO2)|Physical examination + ALS Functional Rating Scale-Revised (ALSFRS-R)||Blood samples will be collected for safety and efficacy assessments:||Hematology|Coagulation Panel|Proinflammatory Cytokines (IL-2, IL-6, TNF-a)|C - Reactive Protein|ALS-specific Quality of Life Survey-revised (ALSSQOL-R)|Chest X-Ray (PA single view)|Electromyogram (EMG)|Magnetic Resonance Imaging (MRI)|Adverse event monitoring|A video recording will be made with the purpose to capture patient's overall status (gait, range of motion assessments, etc.). | ALS |
| 53 | NCT04008329 | Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron disease (MND), which is characterized with highly clinical heterogeneity and no effective treatment is available now. The purpose of this registered cohort is to observe the natural history of ALS patients in China, and then identify some factors correlated with disease progression. Besides, ALS-related gene mutations will be screened and explore novel disease causing gene as well. | ALS |
| 54 | NCT00537641 | Amyotrophic Lateral Sclerosis (ALS), also known as "Lou Gehrig's Disease", is a fatal disorder that causes breathing failure due to progressive weakness of the muscles of breathing. Breathing assist devices known as noninvasive ventilation (NIV) are offered to ALS patients when their breathing function worsens. These devices deliver breathing assistance via a mask on the nose or nose and mouth, and are thought to be particularly important to be used during sleep, when breathing often becomes more shallow and irregular. However, although these devices have become the standard of therapy in ALS patients once their lung function worsens, it remains unclear how effective these devices actually are when a patient is sleeping, partly because of the practical difficulties in applying the device properly and keeping it applied throughout the sleep period, and partly because they are most commonly prescribed without objective evidence regarding how much breathing support the patient needs as the disease progresses and the breathing muscles weaken further. | ALS |
| 55 | NCT03892382 | Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive loss of central and peripheral motor neurons. ALS leads to death usually within 3 to 5 years from the onset of the symptoms. Available treatment can prolong the disease duration but cannot modify the disease course. Apathy is a frequent complication of ALS, which negatively influences quality of life (caga et al. 2018) and is an independent poor prognostic factor for survival (Caga et al. 2016). Similarly, the depression is also a frequent complication of ALS. Repetitive Transcranial Magnetic Stimulation (rTMS) is a noninvasive method of modulation of brain plasticity with confirmed beneficial effect on apathy in several neurologic and psychiatric conditions like mild cognitive impairment (Padala et al. 2018), stroke (Sasaki et al. 2017), Alzheimer disease (Nguyen et al. 2017) and schizophrenia (Prikryl et al. 2013). The purpose of this study is to compare the effectiveness of rTMS in improving the apathy in patients with ALS with placebo stimulation and - as a secondary outcome - depression in patients with ALS.||Intervention will include ten daily sessions of rTMS. In each session 3000 magnetic pulses will be administered over the left dorsolateral prefrontal cortex. Stimulation intensity will equal 120% of the motor threshold value for the right first dorsal interosseus.||Assessment of apathy and of depression and daily functioning will be made before and after therapy, as well as two and four weeks later. | ALS |
| 56 | NCT00753571 | This study will examine the effectiveness of Cistanche Total Glycosides(CTG) in treating patients with amyotrophic lateral sclerosis (ALS) - a fatal neurological degenerative disease that causes adult-onset, progressive motor neurons loss in the spinal cord, brain stem and motor cortex. Patients develop progressive wasting and weakness of both upper and lower limbs, bulbar and respiratory muscles. Usually death from respiratory failure typically is within 3-5 years of diagnosis. Although there are various treatments for ALS, riluzole is the only approved treatment to delay the disease progression. Cistanche Total Glycosides is an approved drug that has protective effects. It acts anti-apoptosis by activating several protective pathways, stimulates neuronal differentiation of adult neural stem cells in the brain, and improves long-term recovery. CTG is a highly attractive candidate for the treatment of neurodegenerative conditions such as ALS.||Patients 18 to 65 years of age who have had mild to moderately severe ALS for 0.5 to 2 years of duration may be eligible for this study. Candidates will be screened with a medical history and possible review of medical records, physical examination, blood test, urine and stool analyses, electrocardiogram, electrophysiological examination, neurological imaging and, for women, a pregnancy test.||Participants will have drug therapy according to randomized number. One group receives CTG while other group receives placebo. For the procedure, patients are given a medication to lessen anxiety and any discomfort. Patients receive drugs for 9 months. The CTG dosage is 1.8g/day. Physical examination and interview, Appel ALS scale and ALS-Functional Rating Scale will be done in 28 days and 3, 6, 9months. Electrophysiological examination will be tested per 3 months. Blood samples will be collected on treat28 days and 3, 6, 9months. | ALS |
| 57 | NCT02164253 | At the end of the study, it will propose to continue the usual quarterly patient follow up, as recommended by the French ALS centers.||Deferiprone can be administered as part of a compassionate use, for patients who want it and who do not have hypoxemia.||We therefore plan a treatment period compassionate relatively short and less than 3 years. | ALS |
| 58 | NCT01277315 | Open Safety and Tolerability study to evaluate a subcutaneous application 100 mg of Anakinra in combination with Riluzol in Amyotrophic Lateral Sclerosis. | ALS |
| 59 | NCT00302198 | Any person who has been diagnosed with ALS by a physician can enroll into this registry.||The information you provide in the ALS registry will be used to evaluate variations in patient care, adherence to standards of care and also to help foster ALS research. An additional focus of this website will be to educate participating patients and visitors to this site about ongoing ALS research. | ALS |
| 60 | NCT01254539 | Patients with Amyotrophic Lateral Sclerosis (ALS) typically endure a progressive paralysis due to the continued loss of motoneurons that leads them to death in less than 5 years. No treatment has changed its natural history. Intraspinal injections of bone marrow mononuclear cells (MNC) have been able to ameliorate the course of ALS in murine models, acting as pumps of trophic factors that keep the motoneurons functional. Moreover, the clinical trial (Study NCT00855400 on www.ClinicalTrials.gov) conducted by our research group to determine the safety and efficacy of Autologous Stem Cell transplantation in Amyotrophic Lateral Sclerosis in humans, found that this procedure is feasible and safe. Continuing with that study, we have designed a phase I/II clinical trial to check the feasibility of the intraspinal and intrathecal infusion of autologous bone marrow stem cells. | ALS |
| 61 | NCT01363401 | Amyotrophic lateral sclerosis is a progressive neurodegenerative disease characterized by motor neuron loss. Despite of many trials for disease-modifying, no treatment has so far changed natural course of disease.||We have performed the pre-clinical and clinical studies using autologous bone marrow-derived stem cells in ALS. We could get the evidence that autologous bone marrow-derived stem cells have dose-dependent effects on SOD1 mice via intrathecal injection. In our results of clinical trial, intrathecal injection of autologous bone marrow-derived stem cells could slow down disease progression and might be used as a disease modifying strategy in patients with ALS.||This study was designed as a single center, randomized, open-label, parallel-group, 2-stage study, and targeted at patients diagnosed with Amyotrophic Lateral Sclerosis(Lou Gehrig's disease). The study consisted of Stage-1 study for safety evaluation and Stage-2 study for efficacy and safety evaluation of the study drug, and at Stage 1, 7 subjects eligible for the inclusion/exclusion criteria received safety evaluation for 28 days of study drug administration in twice under the protocol, and then followed Stage 2. To decide whether the study can be proceeded in 2 stages, ADR(CTCAE Version 3.0, ≥grade 3) should not appear in initial 7 subjects.||Data obtained from subjects of this study were analyzed into three: Safety Analysis, ITT(Intent-To-Treat) Analysis, and PP(Per Protocol) Analysis. However, in case of phase 1, only safety analysis was conducted, and in case of phase 2, all of safety, ITT, and PP analyses were conducted.||For ITT Analysis, all the subjects whose data on primary efficacy endpoint could be obtained following the administration of investigational drug were analyzed in analysis among subjects who were administered the investigational drug once at least. Also, Modified ITT Analysis, including 7 subjects at Stage 1, was carried out. | ALS |
| 62 | NCT02869048 | Amyotrophic lateral sclerosis (ALS) is a progressive, deadly, neurodegenerative disease which affects the upper and lower motor neurons. This leads to profound muscular dystrophy, hyperreflexia, fasciculations and paresis of the bulbar as well as the skeletal musculature. ALS causes increasing physical fatigue and the patients soon become bedridden and respiratory insufficient.The diagnosis ALS is made according to the El Escorial revisited. Often clinical and neurophysiological tests must be repeated (1-4).||In Denmark the incidence of ALS is 1-2/100.000 and the prevalence is 4-6/100.000. The average survival time from the time of the diagnosis is 3 years but with great variance. (5+6)||Today the pathogenesis is still unknown and no treatment can stop the progression of ALS. Treatment with riluzole seems to prolong the median time of survival for 2 or 3 months (7).||Most likely, a future medical treatment requires a better understanding of the pathogenesis as well as the pathophysiology of ALS. This present study aims to do so based on the hypothesis that ALS partially or fully is caused by complement activation.||The complement system is a complex system consisting of proteins in plasma as well as membrane bound proteins which together complement the antibody-based immune system. The complement system is a self-perpetuating cascade system which is activated through different pathways. It works by opsonisation where complement proteins bind to microorganisms to activate and target granulocytes, monocytes and macrophages. The complement system also causes cytolysis of microorganisms via MAC (membrane attack complex) by activation of the mast cells. It also inactivates and eliminates burned out immune complexes as well as performing apoptotic renovation.||A recent pilot study of Neuromyelitis Optica has shown how the complement system play a central part in the pathogenesis of a disease that previously was wrongfully perceived as an early stage of Disseminated Sclerosis. These findings resulted in medical treatment with anticomplement (equlizumab) with promising results (8). It is possible that similar pathogenetic mechanisms could be the molecular basis of ALS.||Different research groups have tried to illuminate how the immune system is involved in the progression of ALS (9-35). Several studies support the hypothesis that the complement system is of crucial importance for the onset and progression of ALS. (9-28)||In several clinical trials with ALS plasma it is concluded that ALS plasma is cytotoxic when incubated with healthy red blood cells or healthy nerve tissue. Some research indicates that the cytotoxicity is caused by the complement system. The results cannot, however, be reproduced consequently in all clinical trials. These trials were conducted decades ago where the methods of detecting complement activity were limited. (9-14)||Several animal trials indicate that ALS starts in the neuromuscular junctions (NMJ) and therefore should be considered a distal axonopathy rather than a central neurological disease, which today is the general perception of ALS. (27-31)||The purpose of the project The aim is to increase the knowledge of the pathophysiology of the disease ALS as this possibly may lead us closer to a targeted medical treatment.||The project group wants to investigate if a previously found, unique cytotoxicity in the ALS plasma can be retrieved (9-14). If this is the case, then the modern methods of today make it possible to detect whether the immune system in general, and in particular the complement system, is causing this cytotoxicity.||The establishment of a national research project about ALS and the complement system by making a research biobank with systematically collected blood and spinal liquid from ALS patients from all over the country will ensure the opportunity to find out if the complement system plays a role in the onset and progression of ALS.||Furthermore a pilot study will be conducted with the purpose to investigate if there is complement activity in the NMJ in patients with ALS as it has been shown in a study of ALS mice. (28)||The hypotheses||ALS is characterized by an abnormal immune response with cytotoxicity and increased complement activity in plasma which is revealed by the following:||Plasma from patients with ALS shows increased haemolytic activity when incubated with red blood cells from healthy subjects.|The complement activity is increased in the plasma from ALS patients compared with plasma from neurologically healthy subjects and subjects with other neurological disease.|The haemolytic activity in the plasma from ALS patients is correlated with the complement activity.|Spinal liquid from ALS patients contains increased complement activity compared with spinal liquid from neurologically healthy subjects and from subjects with other neurological disease.||Patients, materials and methods:||Clinical trial 1(CT1): Haemolytic activity and the complement system in ALS plasma||Number of subjects: 25 patients with ALS, 25 patients with other neurological disease, 25 healthy volunteers||The course of CT1: A blood sample is taken from each patient. The red blood cells and the liquid part of the blood, the plasma, are separated. The red blood cells from different subjects are incubated in an other subjects plasma.The same trial course is repeated after inactivation of the present complement system both by heat and by anti-complement.||Clinical trial 2(CT2): Case-control study aiming to mapping the complement system||Number of subjects:100 patients with ALS, 100 patients with other neurological disease and 100 neurologically healthy patients||The course of CT2:Blood samples and cerebrospinal fluid are prepared and then freezed in a research biobank. Then the samples from the 3 groups of subjects are analysed and compared focusing on the complement system: The complement activation potential is measured in the biological material. A cytokine profile is made as well as mapping the acute phase reactants by multiplex assays. Furthermore the RNA expression profile is made on a cell pellet stabilised with RNA later.||Clinical trial 3(CT3): The complement system of ALS patients over time - a cohort study Number of subjects:20 patients with ALS (subset from CT2)||The course of CT3: Every sixth month the course from the CT2 is repeated. The activity of the complement system in each patient with ALS is analyzed as the disease progresses.||Clinical trial 4(CT4): Searching for complement activity in the NMJ of ALS patients||Number of subjects:10 patients with ALS||The course of CT4: The muscle biopsies are taken and immediately brought to the Dep. of Pathology at Rigshospitalet. Then thin layers of tissue are stained in order to analyze the muscle fibers and the NMJ as well as detecting presence of complement activity.||Conducting the study The project consists of four clinical trials. Inclusion of the subjects is done together with staff in ALS outpatient clinics at hospitals all over the country and subjects for the control groups are included according to the list of inclusion sites below.||Inclusion sites:||ALS outpatient clinic, Neurological clinic, Rigshospitalet Glostrup (CT1+2+3+4) Contact: Chief physician Elisabeth Elmo Neurological Clinic, Rigshospitalet Glostrup (neurological control group, CT1+2) Contact: Professor, Chief physician, dr.med. Rigmor Højland Jensen Neurosurgical Clinic, Rigshospitalet (neurological control group, CT2) Contact: Professor, chief physician, dr.med. Marianne Juhler ALS outpatient clinic, Neurological Dep., Bispebjerg Hospital (CT2) Contact: Chief physician Merete Karlsborg ALS outpatient clinic, Neurological Dep., Roskilde Hospital (CT2 + 3) Contact: Chief physician Helle Thagesen ALS outpatient clinic, Neurological Dep., Odense University Hospital (CT2) Contact: Chief physician, dr.med. Matthias Bode ALS outpatient clinic, Neurological Dep., Aarhus Hospital, Nørrebrogade (Clinical Trial 2) Contact: Chief Physician, ph.d. Anette Torvin Gildhøj Private Hospital, Brøndby (Neurologically healthy control group, Clinical Trial 2) Contact: Anaesthesiologist Niels Anker Pedersen||Power calculations CT1: Haemolytic activity and the complement system in ALS plasma The study Overgaard et al. (18) found a mean difference of about 0,20 (SE 0,052 in the ALS group, N=20, SD 0,22) in the absorbance (415 nm and 5 hours of incubation) between ALS patients and healthy bioanalysts. With α=0,05 og beta=0,20 corresponding to power 0,80 we need to include 21 subjects. As possible drop outs and technically failed are considered tests the investigators choose to include 25 subjects in each group. (36)||CT2: Case-control study mapping the complement system The number of subjects in each group is in this case-control study calculated with α=0,05 The investigators compare the complement activation potential of 3 groups with same amount of subjects in each. In healthy subjects the complement activation potential is 100 % with a normal area ranging from 50-150 % and where the prevalence of low complement activation potential (under 50 %) is under 10 %. With power =0,80 it is calculated to be necessary to include 100 subjects in each group. Hereby it is possible to find statistically significant differences between the groups corresponding to an odds ratio of 2,3, which would correspond to 20 % of ALS patients having a low complement activation potential caused by increased complement activity. (36)||CT3: The complement system of ALS patients over time - a cohort study This is a hypothesis generating study. It is expected that the included 20 ALS patients in this cohort will be a subset from Clinical Trial 2. As a control group at baseline the neurologically healthy control group from Clinical Trial 2 will be used.||CT4: Searching for complement activity in the NMJ of ALS patients There is no previous studies describing the complement activity in the NMJ in living humans. It is therefore not relevant to make a calculation of power.||Data processing CT1: Haemolytic activity and the complement system in ALS plasma Comparing the degree of haemolysis between the ALS patients and the control groups t-test and one way ANOVA are used. For calculating the cut-off values the investigators use receiver operating characteristic (ROC) curves.||CT2: Case-control study mapping the complement system Comparing the concentration of complement and the complement activation potential between ALS patients and the control groups t-test and one way ANOVA are used. In order to calculate the odds for low complement activation potential in the ALS group compared with the control groups the investigators use logistic regression. For calculating the cut-off values receiver operating characteristic (ROC) curves are used.||CT3: The complement system of ALS patients over time - a cohort study As in Clinical Trial 2. Furthermore, regression analysis of the complement activity as a function of time since the onset of ALS, gender, age, subtype of illness and disease progression are conducted.||CT4: Searching for complement activity in the NMJ of ALS patients As in CT2. The degree of complement deposition and muscle pathology is described qualitatively and a blinded scoring in "normal", "light degree" and "severe degree" of changes is conducted. This will be compared quantitatively with 2 x K tables and non-parametric statistics.||Dissemination of results The results of the project will be published in international peer reviewed, journals. Both positive and negative findings will be published.||Perspectivation With the establishment of a big national ALS research biobank it will be possible to conduct many future research projects. Continuous research in ALS is paramount for ALS patients nationally as well as internationally in order to maintain hope for an efficient medical treatment for this aggressive disease is found in the future. | ALS |
| 63 | NCT03693781 | Recent evidence supports the disruption of the ubiquitin-proteasome-system and autophagy as central events in ALS. ALS is characterized by the presence of misfolded proteins prone to oligomerize into aggregates, which exert a toxic effect by affecting several intracellular functions. Heat shock protein B8 (HSPB8) recognizes and promotes the autophagy-mediated removal of misfolded mutant SOD1 and TDP-43 fragments from ALS motor neurons (MNs). Moreover, HSPB8-BAG3-HSP70 maintains the so called "granulostasis", a surveillance mechanism that avoids the conversion of dynamic stress granules (SGs) into aggregation-prone assemblies, which are a hallmark of ALS.||Colchicine enhances the expression of HSPB8 and of several autophagy players while blocking TDP-43 accumulation in neurons. Moreover, given the cross-talk between infalmmation and autophagy, the well-known antinflammatory action of Cochicine may contribute to cell homeostasis.||Based on these premises, this is a phase II randomized, double-blind, placebo-controlled, multicenter (9 MND Centres in Italy: 2 centres in Milan, Pavia, Turin, Modena, Padua, Rome, Naples, Bari), clinical trial to test efficacy of Colchicine in ALS. | ALS |
| 64 | NCT00159198 | The objective of this study without direct individual benefit is to confirm the linkage with one or another region of the two identified regions (chromosomes 9 and 15) or to identify a new implicated chromosomal region, and then to reduce the linkage interval in order to identify the responsible gene(s) and characterize the mutations with the study of at least 9 families with FTD and ALS. | ALS |
| 65 | NCT00876772 | After randomization, there is a placebo-controlled parallel group treatment with 10 mg OLN in combination with the standard treatment of Riluzole (100mg/day)(Group 1) in comparison to treatment with placebo in combination with 100 mg RIL (Group 2). Study drug will be provided as 5 mg tablets. OLN will be begun in an initial dosage of 5 mg/day for one week. The intake will occur in the evening hours in the form of a capsule containing 5 mg OLN. The evening dose of Riluzole can be taken together with the OLN medication. After one week (day 8), the dose will be increase to 10 mg OLN/day, which will be taken in the form of two capsules at the same timepoint in the evening hours. This dose will be continued for 51 weeks. | ALS |
| 66 | NCT01622088 | Amyotrophic Lateral Sclerosis (ALS) is a rapidly progressive, degenerative disease of motor neurons in the brain and spinal cord that leads to muscle atrophy and spasticity in limb and bulbar muscles resulting in weakness and loss of ambulation, oropharyngeal dysfunction, weight loss, and ultimately respiratory failure. The purpose of this study is to collect long-term safety data from subjects with Amyotrophic Lateral Sclerosis (ALS) exposed to dexpramipexole. | ALS |
| 67 | NCT00983983 | Weight loss is a common and severe symptom of amyotrophic lateral sclerosis (ALS), caused both from inadequate calorie intake and an increased metabolic rate. People with ALS are generally instructed to increase their calorie intake; however, the ideal amount and type of calories has not been studied. Several studies in an animal model of motor neuron disease have shown that a high fat/high calorie diet can increase survival by as much as 38%. Mice on a high fat diet also live longer than mice fed diets consisting of high protein or high sugar. We are therefore conducting a phase II safety, tolerability, and preliminary efficacy trial in ALS of high fat versus high calorie versus normal diet. The normal diet will be calculated based on the number of calories needed to replace each participant's measured daily calorie requirement. | ALS |
| 68 | NCT00673140 | As a motor neuron disease, ALS causes muscle weakness and atrophy throughout the body as both the upper and lower motor neurons degenerate, ceasing to send messages to muscles. Unable to function, the muscles gradually weaken, develop fasciculations (twitches) because of denervation, and eventually atrophy due to that denervation. The patient may ultimately lose the ability to initiate and control all voluntary movement except of the eyes.||Observations from our research studies indicate that, far infrared rays provide energy to the body, improve the autonomic functions of the nervous system, restore the functions of the endocrine system, strengthen the immune system, improve blood circulation and increase the level of oxygen in the cells and promote the regeneration of muscle cells, nerves and brain cells.||It is hereby postulated that irradiation using far infrared, with wavelength between 5 to 20 microns, of the central nervous system, the endocrine system and the whole body could prevent, control, manage or possibly lead to complete rehabilitation of people who have ALS. | ALS |
| 69 | NCT04293484 | Amyotrophic Lateral Sclerosis (ALS) is a motor neuron disease, which is a group of neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. The disorder causes muscle weakness and atrophy throughout the body due to the degeneration of the upper and lower motor neurons. Current drugs approved for ALS treatment only modestly slow disease progression.||Transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebral excitability in several neurodegenerative disorders and modulate intracortical connectivity measures.||The present randomized, double-blind, sham-controlled study followed by an open-label phase will investigate a repetition of two-weeks' treatment with bilateral motor cortex anodal tDCS and spinal cathodal tDCS, after a six months interval, may further outlast clinical improvement in patients with amyotrophic lateral sclerosis and modulate intracortical connectivity, at short and long term. | ALS |
| 70 | NCT01257581 | Amyotrophic lateral sclerosis (ALS) is a rare, neurodegenerative disorder that results in progressive wasting and paralysis of voluntary muscles. It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown.||In this double blind, randomized, selection design trial, researchers will evaluate the safety and effectiveness of creatine and tamoxifen in volunteers with ALS. There are a large number of potential drugs that may improve the survival or slow down the disease progression in people with ALS. The current strategy is to test one drug at a time against placebo. "Selection Design" is a different type of study design. A Selection Design study uses multiple drugs to screen against each other and picks the winner to take to a larger study. This design can speed the search for effective drugs to treat ALS. In this Selection Design study, each volunteer will take one active study drug (creatine 30gm, tamoxifen 40mg, or tamoxifen 80mg) and one placebo.||Approximately 60 eligible volunteers with ALS will be recruited from multiple centers in the US that belong to the Northeast ALS Consortium (NEALS). Volunteers will be randomly assigned equally to the three treatment arms: creatine 30gm/day, tamoxifen 40mg/day and tamoxifen 80mg/day. Volunteers will take study treatment for 38 weeks. After screening and randomization, volunteers will be followed at weeks 4, 10, 18, 28 and week 38. A final telephone interview will occur at week 42 (off study drug). | ALS |
| 71 | NCT00855400 | Patients with Amyotrophic Lateral Sclerosis (ALS) typically endure a progressive paralysis due to the continued loss of motoneurons that leads them to death in less than 5 years. No treatment has changed its natural history. Intraspinal injections of bone marrow mononuclear cells (MNC) have been able to ameliorate the course of ALS in murine models, acting as pumps of trophic factors that keep the motoneurons functional. We have designed a phase I/II clinical trial to check the feasibility of this approach in humans. | ALS |
| 72 | NCT02670226 | Amyotrophic Lateral Sclerosis (ALS), the most common MND, is a fatal adult-onset neuromuscular disease. Due to clinical heterogeneity and absence of biological tools to diagnose ALS, the delay between the first symptoms and diagnosis averages 9-13 months. A group of pathophysiological processes, including oxidative stress and glutamate-mediated excitotoxicity contribute to cell death, but the triggering factor, the timing and the interaction of different cellular events await elucidation [2]. Unknown pathogenesis for most patients means few available treatments. The search for biomarkers that can aid diagnosis, characterize phenotype, define pathophysiology, identify endpoints in trials and measure disease progression is of utmost importance for the field. Some studies have advocated that muscle per se may be impaired by pathogenesis of the diseases. Muscle has been poorly studied and its central role in energetic metabolism suggests that this tissue, quite easily available, should be more analyzed to find biomarkers and to compare muscular metabolism with those of brain and overall body. Specific aims of our subjects are:||Specific aims are focused on:||the acquisition of metabolites profiles of the muscle, blood and satellite cells using an analytical platform enable a deep exploration. For that, the use of three analytical modalities (NMR, mass spectrometry coupled to GC or UPLC) ensures the best coverage of the metabolite population with a high range of concentration variability and molecular diversity.|the building of metabolites profiles models that discriminate pathological and control situations.|the identification of metabolites implicated in the discriminant model.|the generation of metabolism pathways hypothesis related to the discriminant model.|the acquisition of transcriptomics data to confirm and add complementary results to metabolomics data | ALS |
| 73 | NCT00420719 | The purpose of this study is to demonstrate the safety and efficacy of the NeuRX RA/4 Diaphragm Pacing Stimulation (DPS) System in conditioning the diaphragm of an ALS patient to improve the quality of life and slow the progression to respiratory failure.||Amyotrophic Lateral Sclerosis (ALS, also known as Lou Gehrig's disease or Motor Neuron Disease) is a progressive neurodegenerative disease of unknown cause. One of the most important effects of progressive neuromuscular weakness in patients with ALS is the effect on respiration. Although ALS has no direct effect on the lung, it has devastating effects on mechanical function of the respiratory system. ALS affects all of the major respiratory muscle groups: upper airway muscles, expiratory muscles, and inspiratory muscles. Therefore, all patients with ALS are at significant risk for respiratory complications. Progressive inspiratory muscle weakness in ALS inevitably leads to carbon dioxide retention, inability to clear secretions and hypercarbic respiratory failure, the major cause of death in ALS.||Synapse Biomedical, in conjunction with Case Western Reserve University and University Hospitals of Cleveland, have evaluated activating the diaphragm with percutaneous intramuscular electrodes implanted laparoscopically. This eliminates any direct contact with the phrenic nerve, allows all circuitry and electronics to remain outside the body, and provides direct, selective activation to each hemidiaphragm. The NeuRx-RA/4 DPS System provides an electrical signal to the motor point of the muscle that causes the diaphragm to contract and allows patients to breathe more naturally.||The NeuRx RA/4 DPS System has been implanted in over 10 individuals with ALS, in a pilot study at the University Hospitals of Cleveland that began January, 2005.||The NeuRx RA/4 DPS System platform, also used for respiratory support for individuals with high-level spinal cord injury, has over 56 years of cumulative active implantation time. The longest term patient was implanted March 6, 2000 and has been using the DPS System as his sole means of respiratory support for over six years.||Given patient results to date the data supports safety and efficacy to proceed to pivotal study in this patient population. With no unexpected significant adverse events reported, the NeuRx RA/4 DPS System has performed reliably and safely.||Device Description: The NeuRx RA/4 Respiratory System is manufactured by Synapse Biomedical. The NeuRx RA/4 System comprises the following components: an external, battery powered Stimulator Device, an associated Programmer/Controller, Intramuscular Electrodes, associated percutaneous Lead Wires, a Surgical Placement Tool Set, and a surgical Mapping Station.||Inclusion Criteria:||Age 18 or older|Participants with familial or sporadic ALS diagnosed as laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria will be eligible|Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with fluoroscopic sniff test or with EMG recordings and nerve conduction times|Forced Vital Capacity (FVC) between 50 - 85% of predicted values to begin screening procedures.|FVC greater than 45% of predicted value at time of surgery.|No underlying cardiac or pulmonary diseases that would increase the risk of general anesthesia greater than the expected risk of the patient with ALS|Negative pregnancy test in females of child-bearing potential|Informed consent from patient or designated representative||Exclusion Criteria:||Preexisting implanted electrical device such as pacemaker or cardiac defibrillator.|Underlying pulmonary diseases that were present prior to ALS that would effect pulmonary tests independent of ALS.|Active cardiovascular disease that would increase the risk of general anesthesia|Current pregnancy or breastfeeding|Hospitalization for a treated active infection within the last 2 months|Significant decision making incapacity preventing informed consent by the subject due to a major mental disorder such as major depression or schizophrenia, or dementia such as having Alzheimer's disease.|Marked obesity | ALS |
| 74 | NCT00706147 | Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Telephonic evaluations at Month-1, 3, 4, 5, 6, 8, and 10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months-1, 3, 4, 5, 6, 8, and 10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month-13 (30 days after the last dose of study medication). | ALS |
| 75 | NCT03113630 | Participants A total of 60 individuals participated in this study, 30 individuals with ALS (18 men and 12 women, mean age 59 years, range 44-74 years) and 30 healthy individuals who formed the control group, which were (equally) matched individually for age and gender with ALS group.||Rating scales For clinical characteristics of the participants, the scales of functional assessment, fatigue and quality of life were applied. As a functional assessment tool, the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS - R) was used, validated in Brazilian individuals with ALS which allows monitoring of symptoms and limitations of daily living activities. To evaluate fatigue during the execution of tasks, were used the Fatigue Severity Scale (FSS) and for the assessment of quality of life, were used the Amyotrophic Lateral Sclerosis Assessment Questionnaire in the Portuguese Language (ALSAQ-40/BR), which is also validated for the Brazilian population with ALS.||Protocol Subjects were randomly divided into three groups, using different interfaces for the acquisition of movement. The description of the task and the RV interfaces that were used are described as follows.||Task Participants performed a task to test communication devices developed by the Information Systems Team at the University of São Paulo. The task was set up as a game in which the goal was to reach as many bubbles displayed on an 11-inch computer monitor, forming seven rows and 18 columns with a total of 126 bubbles. This required individuals to be able to use a range as is typically required in communication systems. The task was divided into two phases: (1) the first phase was characterized by identification of dexterity zone or range of reach, in which the subject had to touch ("burst") the largest possible number of bubbles (changing bubble color from blue to gray) in a set time of 30 seconds, identifying the range zone; (2) the second phase was characterized as the persecution stage, at this time the researcher defined a central bubble (usually chosen in the center of the skill area, on the bottom line), which changed the color to red. From this moment the individual pursued random bubbles that appeared in their range zone, alternating with a return to the central bubble. This phase was carried out for 30 seconds. To motivate, the task randomly provided bubbles outside the range zone and generated a greater challenge to the individual. The software generated information of the coordinates x, y (row and column) where the bubble was touched and the time the bubble was touched. During task execution, the participant received feedback of the number of bubbles touched, the remaining playing time and the total number of points obtained in attempts, thus observing the performance of the participants.||Interfaces To perform the task were used 3 different interfaces: two interfaces without physical contact, being the Kinect® for Windows from Microsoft, composed of a traditional RGB camera and an infrared depth sensor (IR) and LMC®, characterized as a small motion sensor that demonstrated robustness to measure the movements of the hand and fingers. The interface with physical contact, the touchscreen, was the computer screen itself, where individuals touched the screen in order to burst the bubbles, performing the task. It is noteworthy that the touchscreen is a sensitive interface, employed through pressure, created in order to interact with digital information, found in a majority of modern consumer electronics, mainly computers, tablets and mobile phones.||Procedures and design Individuals who participated in the study gave written informed consent and then were sent to a reserved and quiet room to perform the tasks only in the presence of the researcher. The computer monitor was positioned on a table in front of the participants. The chair was adjusted in accordance with the size and need of the individual, with a footrest available if needed. For wheelchair users, their own wheelchair was used. After the necessary adjustments to perform the task, questionnaires and functional assessment scales were applied; then the researcher provided verbal instructions and performed a demonstration of interfaces according to each task (Kinect® for Windows, LMC® or touchscreen). Subjects were instructed to use the dominant hand (i.e., the least affected side) for all interfaces used during the game.||For the acquisition phase a target was set of 300 bubbles to be touched in the definition phase of the dexterity zone. There were 126 bubbles presented during each attempt; therefore it took at least three attempts to reach the proposed goal. Soon after the step establishing the dexterity zone, the researcher defined the central bubble and began the stage of chase area. In addition to the acquisition phase, all groups performed a retention test after 5 minutes with the completion of only one attempt. After the retention test, two transfer tests with the change of interfaces were performed. | ALS |
| 76 | NCT00069186 | Introduction: Twenty-one ALS patients were enrolled in a placebo controlled pilot study at the Carolinas Neuromuscular/ALS-MDA Center, The University of Texas Health Science Center at San Antonio and The University of New Mexico at Albuquerque. At all time points sampled over a nine month period, patients taking creatine monohydrate had either a significantly greater improvement in their strength or a more modest decline compared to the patients taking placebo. Overall analysis of variance is significant for both an effect of the drug (p=0.002) and time (p< 0.001).The pilot study also showed that quality of life, as measured by ALSFRS-R, correlated significantly with the observed changes in muscle strength (MVIC).||Phase III Study: The primary objective of this study is to determine whether treatment with creatine monohydrate results in an increase in muscle strength relative to placebo in patients with amyotrophic lateral sclerosis (ALS), after three months, and at the end of a nine-month treatment period.||The study is a Phase III, eight-center, double-blind, placebo-controlled, randomized clinical trial designed to evaluate the safety and efficacy of creatine monohydrate in patients fulfilling the eligibility criteria. The subjects (n=156) will be randomized in a 1:1 ratio to receive treatment of highly purified creatine monohydrate or placebo (Dextrose, USP) for nine months. The subjects will be administered 10 grams of creatine monohydrate per day for the first five days, and then 5 grams per day thereafter. Each subject will be followed for the nine-month treatment period.||The primary outcome measure for the study is change in upper extremity motor function after three weeks, and at the end of a nine-month treatment period as tested by MVIC. Strength in ten arm muscles will be measured (bilateral shoulder and elbow flexion/extension and grip).||Patient safety will be assured by ongoing review of reports of adverse events, clinical laboratory data, and measurement of vital signs. These tests include: measurement of MVIC and muscle fatigue, measurement of FVC, completion of ALSFRS-R and SF-12 quality of life instruments, review of potential adverse effects, determination of vital signs and weight, serum creatinine and BUN, and urine dipstick for protein. | ALS |
| 77 | NCT00035815 | The objective of this trial was to determine whether IGF-1 (MyotrophinTM) slows progression of weakness in amyotrophic lateral sclerosis (ALS). Three hundred thirty patients with ALS from 20 medical centers participated in this double blind, placebo-controlled two-year study. Half the patients received IGF-1 and the other half received placebo. The drug will be administered twice a day.||ALS is a neurodegenerative disorder that causes progressive muscle weakness and loss of motor neurons. IGF-1 is a neurotrophic factor essential for normal development of the nervous system and shows protection of motor neurons in animal models and cell culture systems. It is thought to block cell death pathways and promote muscle re-innervation and axonal growth and regeneration. | ALS |
| 78 | NCT01777646 | This is a phase IIa prospective, open label, dose-escalating, three patient-group clinical study, to evaluate the safety, tolerability and preliminary efficacy of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a potent treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early disease stages. This study is a single center trial. It is anticipated that the study will be conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. In addition, ALS patients could also be referred to the clinical site above by other medical centers.||All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage ALS disease with duration of less than 2 years. ALS patients identified as "predisposed" will be approached and requested to sign an Informed Consent Form (ICF). Overall, 14 patients will be recruited.||Treatment will start with the lowest dose (94x106 cells) and the dose will be increased to the next medium and high dose (141x106 and 188x106 respectively), for the next patients group only following safety analysis.||The expected duration of patient screening period prior to enrollment into this study is in-between two weeks up to 2 days prior to the study enrollment day during visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed for every month during a "run in period" of 3 months for determination of the progression rate of the disease (allowing a time window of ± 5 days for all visits). During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration (BMA) procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last "run in period" visit, patients will undergo the treatment and MSC-NTF will be transplanted by IM+IT to the early ALS patients.||After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months (allowing a time window of ± 5 days for all visits). Treatment safety, adverse events and exploratory parameters, to establish ALS progression rate assessment of the disease will be recorded throughout the duration of the "run in period" and the post treatment follow up period. | ALS |
| 79 | NCT00230074 | This is a study to evaluate the safety and clinical effects of 4 oral doses of TCH346 compared to placebo in patients with mild or mild to moderate stages of ALS. | ALS |
| 80 | NCT03579017 | Screening of cognitive and behavioral impairment is a distinct recommendation in ALS-specific health-care. Thus, a rapid screening tool valid for use in Norway is urgent. However, cognitive assessment for patients with ALS can be difficult due to the complexity of cognitive impairment, as well as motor challenges with writing, drawing and speaking. Therefore, only ALS-specific, multi domain screening instruments with integrated behavioral sections should be used. Internationally, the Edinburgh cognitive and behavioral amyotrophic lateral sclerosis screen (ECAS), is recommended for the purpose. Besides being quick and easy to administer, the ECAS is shown to be sensitive and have high specificity to ALS-specific dysfunction and behavioral changes. The introduction of ECAS has probably contributed to a more nuanced picture of cognitive impairment in ALS than previously assumed. Therefore the ECAS has been translated and culturally adapted into Norwegian (ECAS-N). Based on scores from healthy people, Norwegian age- and educational-adjusted norms for verbal fluency (n=277) and cut-off-scores (n=85) for abnormal findings are established. However, further investigation of psychometric properties of the ECAS-N is needed. The objectives of the study are: 1. To investigate if the ECAS-N reflect cognitive impairment (internal consistency), and is robust to measurement errors due to different times of testing (test-retest reliability) and different raters (interrater reliability) 2. To investigate if the ECAS-N can be used to distinguish between people with ALS-specific cognitive impairment, and those who do not have cognitive impairment, and those who have cognitive impairment due to other disorders (construct validity). | ALS |
| 81 | NCT03766321 | The study will include 42 ALS patients with 2:1 allocation in 2 groups of subjects (28 FMT vs 14 placebo); computerized randomization will be stratified by progression rate (ΔFS) </≥0.7. Randomization time will last 18 months. Treatment will be double blinded to patients and physicians, and will be done at baseline and at month 6. FMT is regarded as the active treatment. Post-treatment follow up will be 6 months.||ALS patients will undergo upper GI endoscopy with small-intestine biopsies (n° 4 biopsies of small intestine, performed with a standard biopsy forces) at baseline and after 6 months. At baseline patients will be randomized (2:1) to either an allogenic (from donors) infusion of collected feces (fecal microbiota transplantation, FMT) (or no procedure in case of allocation to placebo) in the duodenum-jejunum. The infusion will be performed through a standard nasojejunal tube, that will be placed during endoscopy. Infusion of feces will be performed at time 0 and repeated at month 6. The patients allocated to placebo arm will not receive treatment, but will undergo intestinal biopsy.||Upper GI endoscopy 12 months after FMT will be performed only to identify specific microbioma and mucosal immunological evaluation. Fecal samples and small intestine biopsy samples (at baseline, before treatment, and at month 6 and 12) will be obtained from patients to perform the gut microbiota typing.||Every endoscopic procedure will be performed with sedation of the patient. Feces for FMT will be obtained by healthy donors for C. difficile infection. Procedures that are usually performed for the selection of donors for transplantation of feces are as follows. Potential donors stool will be chosen in healthy volunteers that will have given a questionnaire with questions about lifestyle, health status, current therapy, etc., significant clinical symptoms of gastrointestinal disease, etc.. Based on this questionnaire, the potential donor will be considered eligible if excluded: I) Habits of life and risk behaviors, II) Concomitant significant known disorders, III) chronic or recent use of concomitant medications that may interfere with the state of the intestinal microflora (eg, antibiotics), IV) Clinical symptoms indicative of gastrointestinal disease or other diseases of importance, V) Personal or family medical history known of neurodegenerative diseases or other autoimmune diseases.||Moreover, each suitable potential donor will be subjected to the following screening tests: I) Examination of stool for Clostridium difficile bacterial pathogens and protozoa and helminths of the small intestine and colon, Vancomycin-resistant Enterococci (VRE ), Methicillin-resistant Staphylococcus aureus (MRSA), Gram-negative Multidrug-Resistant Organisms (MDR), II) Serological screening for hepatitis virus A,B and C, HIV 1-2, Treponema pallidum, H. pylori, blood count with differential, dose transaminasemia, creatinine and C-reactive protein.||Potential donors negative for this screening will be considered definitively suitable and will be invited to give a stool sample to prepare than for the fecal transplant. The donation will be made in the appropriate circles in the Department of Internal Medicine and Gastroenterology, and the preparation of faeces (manual homogenization in 500 mL of saline solution) for infusion will be performed at the Unit of Analysis 2 ° (Virology and Microbiology).||Analysis of T cell sub-populations will be performed both in peripheral blood and gut mucosa: especially the ratio T Regulatory cells (Tregs)/Th17 cells A Contract Research Organization (CRO) will be in charge for study monitoring. | ALS |
| 82 | NCT02794857 | This is a randomized, double-blind, placebo-controlled study of NP001 in subjects with ALS and evidence of elevated systemic inflammation. Subjects will be allocated (1:1) to NP001 and placebo. Drug or placebo will be given intravenously. | ALS |
| 83 | NCT01232738 | The specific aim of this screen study is to determine whether rasagiline is safe in this patient population and if the drug has the potential to slow ALS disease progression | ALS |
| 84 | NCT02710110 | This research study will measure the maximum inspiratory and expiratory pressure with secondary measures of respiration, swallow, cough, quality of life and global disease progression following twelve-weeks of treatment compared to the sham group.||As a participant two evaluations at the University of Florida Swallowing Systems Core laboratory located at Shands Hospital, Gainesville will take place. Each will take approximately two-hours and these will be spaced exactly three-months apart. During each evaluation tests will be performed to look at breathing, swallowing, and ability to cough doing standard clinical exams. In addition, some surveys about eating, speaking and quality of life will be taken.||Breathing Exercises: a home research therapist will train the participants how to use the hand-held respiratory trainer. Training for both treatment groups will be very similar, except the PowerLung trainer device will have an additional spring load valve inside it that will place a force on the respiratory muscles during training. The other breathing trainer will not have this spring so that no resistance will be placed on the respiratory muscles during training and this will represent an aerobic respiratory treatment. The breathing exercises will be completed five days a week for a total of three months (a total of 60 therapy sessions). During each session, a total of three sets of ten repetitions of breathing exercises will be performed. Once a week the home research therapist will visit and guide participants through the breathing exercise. | ALS |
| 85 | NCT02193893 | Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is less that 5 years. The cause is generally unknown and there is no effective treatment. Patients with ALS typically exhibit a progressive paralysis due to the continued loss of motoneurons. Intraspinal injections of bone marrow mononuclear cells have been able to ameliorate the course of ALS in murine models. The purpose of this prospective, nonrandomized, open label, pilot study is to conduct the investigation of the safety and efficacy of infusion of autologous bone marrow-isolated stem/progenitor cells with different selected phenotypes into the subjects with diagnosed ALS. Especially, this clinical trial is designated to test the therapeutic (pro-regenerative and neuro-protective) functions of different stem/progenitor cell populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage of ALS with the duration of disease less than 6 months and patients diagnosed with advanced stage of ALS disease with duration of 6-12 months will be recruited and allocated based on their disease severity to two treatment groups: Group I - patients of early ALS disease stage and Group II - patients of advanced ALS disease. Next, autologous bone marrow-isolated stem/progenitor cells administration to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC), functional rating scale (FRS) and maximum voluntary isometric contraction-arm (MVIC-arm) evaluation, to establish ALS progression rate will be recorded throughout the duration of the post-treatment follow up period. | ALS |
| 86 | NCT04055623 | Based on data collected in a previous study with a small group of patients, evidence was found to show that interfering with the immune system using Treg cells slowed ALS disease progression. It is known that Treg cell numbers and function are reduced in patients with ALS and in some patients with lower Treg cells, they have a more marked rapid progression of their ALS. For this study, there are two sites (in Houston, TX and Boston, MA) in which Tregs will be taken from participants, increased or expanded outside the body, and then re-administered back to the participants from which the Tregs came.||This study has two parts:||the first period is a 6-month phase 2a, 2-center, randomized, placebo-controlled clinical trial studying the biological activity, safety, and tolerability of the increased / expanded Tregs administered intravenously (IV) with subcutaneous low-dose Interleukin-2 (IL-2) in 12 adults with ALS. IL2 helps regulate the immune system's white blood cells.|The second period is a 6-month open-label extension in which all participants will receive their own expanded Treg cells administered intravenously in combination with subcutaneous low-dose IL-2.||This study is studying whether the enhancement of Treg numbers and function will slow disease progression.||In the first study of Tregs, we completed a single-center, open-label phase I study of Tregs from people with ALS. Tregs were increased outside the body and returned back to the individual Treg owners in multiple doses every 2 to 4 weeks. This early study provided evidence in a small group of patients that treatment with autologous Tregs may be effective in slowing ALS progression. | ALS |
| 87 | NCT01786174 | The primary objective of the study is to determine the acute safety and tolerability of oral administration of Gilenya (fingolimod) 0.5mg daily vs. matched oral placebo administered daily.||The primary outcome measure will be safety and tolerability; safety will be assessed by the occurrence of adverse events and clinically meaningful changes in vital signs, ophthalmologic examination, physical examination, electrocardiogram and standard clinical laboratory blood tests, and tolerability will be defined as the ability of subjects to complete the entire 4-week study.||The secondary outcome measure will be the measured effect of the treatment on circulating lymphocyte populations in patients with ALS.||Exploratory outcome measures will include the rate of decline of the ALS Functional Rating Scale (Revised) (ALSFRS-R) and Slow Vital Capacity (VC) during the course of treatment.||This study will be conducted in subjects who meet the El Escorial criteria of possible, laboratory-supported probable, probable, or definite criteria for a diagnosis of ALS. At screening, eligible subjects must be at least 18 years old, must have an SVC ≥ 65% of predicted capacity for age, height and gender, and must provide written informed consent prior to screening. Subjects on a stable dose of riluzole and those not taking riluzole, and women of child-bearing age at screening are eligible for inclusion as long as they meet specific protocol requirements.||Subjects will remain on randomized, placebo-controlled, double-blind treatment until the Week 4 visit. Each randomized subject will also have a Week 8 Follow-up Telephone Interview to assess for adverse events (AEs), changes in concomitant medications and to administer the ALSFRS-R. | ALS |
| 88 | NCT02478450 | This study is a non-randomized, open-label, partially blinded, sequential cohort, dose-escalation study designed to obtain preliminary data on the safety, tolerability, and early efficacy of Q-Cells® transplantation in subjects with ALS. Following an initial cohort receiving cell transplants unilaterally in the lumbar spinal cord, subsequent cohorts will receive escalating doses transplanted unilaterally in cervical spinal cord. Subjects and outcome measure assessors will be blinded to side of treatment. The study will be conducted at sites with extensive clinical experience with the care of patients with ALS.||The study is planned to enroll up to 30 subjects over 24 months. Each subject will receive a single time point administration of Q-Cells®: with 5 or 10 (dependent upon dose level) transplantation foci targeted to the anterior horn in either the lumbar or cervical spinal cord.||The study consists of Screening, Pre-operative/Treatment, and Post-treatment study periods. The study data will be assessed for safety and efficacy after the last subject has completed the 9-month study visit. Following the 9-month study period, subjects who consent will continue to be followed for safety and efficacy long-term in a separate protocol. | ALS |
| 89 | NCT01984814 | Survival duration in Amyotrophic Lateral Sclerosis patients who received cellular transplantation was compared to patients who did not receive cellular transplantation. Kaplan-Meier survival analysis was used for this comparison. | ALS |
| 90 | NCT04233099 | SAMPLE COLLECTION: Saliva collection from all the selected subjects will be performed following the Salivette (SARSTEDT) manufacturer's instructions. To limit variability in salivary content not related to ALS, saliva will be obtained from all subjects at a fixed time, after an appropriate lag time from feeding and teeth brushing. Pre-analytical parameters (i.e. storage temperature and time between collection and processing), dietary and smoking habit will be properly recorded. Briefly, the swab will be removed, placed in the mouth and chewed for 60 seconds to stimulate salivation. Then the swab will be centrifuged for 2 minutes at 1,000 g to remove cells fragments and food debris. Collected samples will be stored at -80° C.||SAMPLE PROCESSING: Before the Raman acquisition, saliva samples will be filtered with different cut-off ranges (3, 10 and 30 kDa), collecting and analysing by RS the eluted sample and discarding the concentrated counterpart. For the Raman analysis, a drop of each sample will be casted on an aluminium foil in order to achieve the Surface Enhanced Raman Scattering (SERS).||DATA COLLECTION: Raman and SERS spectra will be acquired using an Aramis Raman microscope (Horiba Jobin-Yvon, France) equipped with a laser light source operating at 785 nm with laser power ranging from 25-100% (Max power 512 mW). Acquisition time between 10-30 seconds will be used. The instrument will be calibrated before each analysis using the reference band of silicon at 520.7 cm-1. Raman spectra will be collected from 15 points following a line-map from the edge to the centre of the drop. Spectra will be acquired in the region between 400 and 1800 cm-1 using a 50x objective (Olympus, Japan). Spectra resolution is about 1.2 cm-1. The software package LabSpec 6 (Horiba Jobin-Yvon, France) will be used for map design and the acquisition of spectra.||DATA PROCESSING: All the acquired spectra will be fit with a fifth-degree polynomial baseline and normalized by unit vector using the dedicated software LabSpec 6. The contribution of the substrate will be removed from each spectra. The statistical analysis to validate the method, will be performed using a multivariate analysis approach. Principal Component analysis (PCA) will be performed in order to reduce data dimensions and to evidence major trends. The first 20 resultant Principal Components (PCs) will be used in a classification model, Linear Discriminant Analysis (LDA), to discriminate the data maximizing the variance between the selected groups. The smallest number of PCs will be selected to prevent data overfitting. Leave-one-out cross-validation and confusion matrix test will be used to evaluate the method sensitivity, precision and accuracy of the LDA model. Mann-Whitney will be performed on PCs scores to verify the differences statistically relevant between the analysed groups. Correlation and partial correlation analysis will be performed using the Spearman's test, assuming as valid correlation only the coefficients with a p-value lower than 0.05. The statistical analysis will be performed using Origin2018 (OriginLab, USA). | ALS |
| 91 | NCT03067857 | A motor neuron disease (MND) is any of several neurological disorders that selectively affect motor neurons, the cells that control voluntary muscles of the body. They include amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP) and pseudobulbar palsy; spinal muscular atrophies are also sometimes included in the group.They are neurodegenerative diseases that cause increasing disability and eventually, death.||In spite of intensive research, motor neuron diseases (MNDs) are still incurable. Some of the key factors in this failure to find a cure have been the lack of human cell-based disease models for molecular analysis and drug screening and the difficulty of obtaining homogeneous populations of specific cell types for clinical applications. Stem cell biology has the potential to transform our understanding of disease processes and to revolutionize our approach to develop novel therapies for MNDs.||In this study, the investigators suggest a protocol for the treatment of MND by transplantation of purified autologous bone marrow-derived stem cells via the intrathecal and intravenous route. | ALS |
| 92 | NCT01551940 | The patient will benefit from an ultrasound guided injection of botulinum toxin A (Botox®) or placebo (NaCl 0.9 %) and will be followed up in consultation at 4, 12, 16 (if reinjection) and 24 weeks. He will be contacted by telephone in 2 and in 8 weeks (percentage of decrease of functional embarrassment, percentage of decrease of salivary secretion rate). He can be able to benefit in the open label phase of a botulinum toxin type A injection at the 12-week follow up if he estimates that first injection was not effective or if the efficiency of the first injection began to become blurred. After the 6 months of the study, the patient will benefit again from the usual follow-up as advised by the French consensus conference in November, 2005. | ALS |
| 93 | NCT03843710 | This is a single-center open label pilot, sequential group, investigator blinded study of the CNS metabolic effects, safety, pharmacokinetics, and pharmacodynamics of CNM-Au8 in patients who have been diagnosed with Amyotrophic Lateral Sclerosis within twelve months of Screening. The Sponsor will select a starting treatment dose of CNM-Au8 for the initial treatment. Investigators and patients will be blinded to each cohort's study dose. Upon completion of the first treatment cohort, the Sponsor will select a single dose or two different doses for the subsequent second cohort from a pre-specified dosing selection plan based on the evaluation of the 31P-Magnetic Resonance Spectroscopy (31P-MRS) changes versus baseline in the first cohort. Up to a total of two treatment cohorts may be studied (n=12 patients/cohort, total n=24 patients). All patients will receive daily oral treatment over twelve consecutive weeks during each cohort's Treatment Period.||There will be three study periods per treatment cohort:||A four-week screening period (Screening Period); A twelve-week treatment period (Treatment Period); A four-week follow-up period (End-of-Study Assessment).||The primary study outcome, CNS metabolic changes, will be assessed based upon each patient's Week 12 study visit versus the pre-treatment baseline. The primary endpoint is the brain metabolic effects of treatment with CNM-Au8 as assessed by an improvement of 31P-MRS assessment of Brain Tissue Cellular Redox Potential defined by the measured tissue ratio of NAD+:NADH concentrations following 12 weeks of once daily treatment. | ALS |
| 94 | NCT03793868 | To measure the effect on motor threshold (MT) by transcranial magnetic stimulation (TMS) after a single dose of perampanel at two dose levels. | ALS |
| 95 | NCT00748501 | SB-509 contains the gene (DNA-a kind of biological "blueprint") for a protein. When a study doctor injects SB-509 into the muscles of your neck, arms and/or legs, the drug enters the muscle and nerve cells around the injection sites and causes these cells to make a protein. This protein causes your cells to increase production of one of your own protein called vascular endothelial growth factor(VEGF-A), which may improve the structure and function of nerves and muscles. In addition, there are changes in the levels of 28 additional proteins in your cells. These proteins function to promote the growth of cells, are structures in cells, help synthesize products, and affect immune cells, and some have unknown functions. This increase in your own VEGF proteins may protect and repair the damaged nerves and muscles caused by ALS. | ALS |
| 96 | NCT01459302 | Participants will be asked to provide a blood sample ( or sometimes saliva or skin sample) and to complete a couple of questionnaires regarding their overall medical health and some environmental risk factors. Medical records will be requested for all those diagnosed with one of the study diseases to allow the researchers to review details of their clinical disease symptoms, neurological exams and test results.||Participants do not need to travel to Massachusetts for this study. Samples can be obtained locally at no costs to the participant. Family members may be included in the study depending on family history and their relationship to the affected individual. | ALS |
| 97 | NCT02124057 | Objectives:||Spinal and bulbar muscular atrophy (SBMA), or Kennedy s disease, is a slowly progressive hereditary motor neuron disease for which there is currently no effective treatment. Whether the liver is affected in SBMA is unclear. Preliminary analysis in SBMA patients has shown changes including increased hepatic fat, which requires additional investigation. Female carriers and patients with motor neuron disease will also participate in the study to evaluate for liver fat and function via imaging and laboratory tests.||Study Population:||We plan to enroll 15 men with genetically confirmed SBMA, 15 age-matched healthy control men, 15 SBMA carrier women, 15 age-matched healthy control women and 15 males with other motor neuron disease patients as disease controls. As of September 2017, recruitment is complete for men with genetically confirmed SBMA (n=15 recruited), age-matched healthy control men (n=15 recruited), SBMA carrier women (n=14 recruited), and 15 age-matched healthy control women (n=14 recruited). Recruitment of motor neuron disease subjects as disease controls for the study began in April 2018 and is ongoing. Our goal is to recruit 12 more disease control subjects.||Design:||Subjects will complete liver evaluations at the NIH that may include blood work, liver MRI imaging with spectroscopy (MRS), ultrasound, and biopsy. Liver biopsy will be performed on a subset of subjects with SBMA only, who have a clinical indication for biopsy analysis. Liver tissue will be analyzed by the NIH Clinical Center Pathology Department, and additional studies will be done in the research laboratory at NIH. Patients may undergo repeated non-invasive testing to determine if the liver findings are changing over time. An evaluation of muscle fat by MRI spectroscopy will be done with a subset of up to 10 subjects receiving the liver studies.||Outcome measures:||Subjects will be assessed using several different types of measurements including blood work for fatty metabolism, muscle function, and hepatic function. Liver biopsies will be used to determine the pattern and degree of fatty infiltration in SBMA patients. Liver and muscle imaging will be used to detect fat. Ultrasound elastography will be used to assess the extent of fibrosis and loss of elasticity in the liver. | ALS |
| 98 | NCT02559869 | In this trial, approximately 200 subjects will participate in this study from 2 Northeast ALS Consortium (NEALS) centers in the United States. Fifty (50) ALS participants will be age and gender matched to 50 participants with no known neurological disorder (healthy controls). Of these, twenty five (25) ALS participants will be age (±5 years) gender and binding affinity (TSPO) matched to 25 healthy controls.||During the enrollment period 200 participants will be screened and 100 participants will ultimately be scanned. There will be a maximum allowed time of 45 days between the screening and baseline visits (1st scan). All 100 subjects will undergo MRI scanning and clinical assessment at the Baseline Visit. Healthy control participants will have no further follow-up visits once they have completed their participation in the screening and baseline visits. Only 50 subjects from this sample will undergo PET scanning. The ALS participants will return for follow-up MRI scanning and clinical assessments every three months and follow-up PET scanning every 6 months over a 12-month period. | ALS |
| 99 | NCT02588807 | This is an open label pilot study, where patients (n=10) with ALS will take a daily nutritional supplement for 8 months. After documenting the ALS symptom history at baseline, the disease severity, and the motor muscles functions will be assessed at baseline and every two months (0, 2 , 4, 6, 8 months of the treatment). Adverse events and side effect will be assessed on every visit and throughout the experiment. In addition, the level of renal function, liver function and electrolytes will be evaluated from blood samples taken at baseline, 4, and 8 months visits. | ALS |
| 100 | NCT00070993 | Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder selectively affecting motor neurons, resulting in progressive weakness. Currently there is no known cure and a specific cause has not been identified. Creatine is a nutritional supplement that improves mitochondrial function and has been shown to protect motor neurons in animal models of ALS. Preliminary research indicates that creatine may also improve strength in patients with ALS. This study will determine the effect of creatine treatment on short-term muscle strength and long-term muscle deterioration in patients with ALS.||Participants in this study will be randomly assigned to receive either creatine or placebo. Participants will be enrolled in the study for 9 months. Quantitative muscle testing will be done weekly for the first 3 weeks; participants will then be followed monthly for the next 4 months and bimonthly for the remainder of the 9-month study. The study will also monitor purposeful exercise to determine if this enhances the benefit of creatine usage on muscle strength. Pulmonary function testing will accompany the muscle testing to determine if creatine strengthens respiratory muscles, thereby enhancing pulmonary function. | ALS |