View clinical trials related to Motor Neuron Disease.
Filter by:The proposed study is an Open-Label, Single-Dose Study to Assess the Safety, and Pharmacodynamics (PD) signals of MRG-001 in Patients with Amyotrophic Lateral Sclerosis (ALS). MRG-001 will be administered subcutaneously 3 times per week for 2 weeks. This cycle will be repeated for 3 months. In total, patients are expected to receive 18 injections over the span of 3 months.
This study aims at evaluating efficacy and tolerability of an ultra-high-caloric, fatty diet (UFD) compared to placebo in patients with amyotrophic lateral sclerosis (ALS).
The goal of this clinical trial is to learn about the effect of communicative interaction on verbal communication in people with amyotrophic lateral sclerosis (ALS) and age-matched speakers. The question is, What are the effects of communicative interaction on verbal communication in people with ALS? Participants will read words and sentences while they are in a solo setting and interactive setting.
Amyotrophic lateral sclerosis (ALS) is a progressive neurological disorder characterized by selective death of upper and lower motor neurons, which leads to severe disability and fatal outcomes. One of the major hallmarks of ALS is the denervation of neuromuscular junctions (NMJs), which is one of the earliest events seen in ALS patients and mouse models of ALS. Under healthy conditions, glial cells called Perisynaptic Schwann Cells (PSCs) have a key role in regulating the stability and maintenance of NMJs, but they only participate in NMJ repair once denervation occurs. Denervation and the subsequent decline in synaptic activity triggers a loss of muscarinic acetylcholine receptors (mAChRs) in the PSC, and the resulting decrease in mAChR-mediated gene expression drives the "repair mode" of the PSC. In assessing the NMJ under conditions of ALS, a scarcity of process extensions in PSCs was observed for months prior to disease onset in the superoxide dismutase 1 (SOD1) mouse model of ALS, indicating inadequate glial repair. Collectively, these preclinical findings support the hypothesis that dampening glial mAChRs will restore the anticipated "repair" response of PSCs in the NMJ. Hence, the use of a selective M3 muscarinic receptor antagonist, Darifenacin, as a disease-modifying therapeutic in familial and sporadic ALS could improve NMJ function, resulting in a beneficial impact on the autonomy and quality of life of ALS patients. The purpose of the current Phase 2 trial is therefore to test the safety, tolerability, and pharmacology of Darifenacin in patients with ALS. Specifically, 30 eligible subjects between 18 and 85 years of age will take 7.5 mg of darifenacin or placebo daily (by mouth) for two weeks followed by an increased dose of 15 mg for the next 22 weeks. The trial will evaluate the effects of this medication on several outcome measures including patient safety, physical and neurological function, muscle strength, depression levels, and NMJ innervation of patients with ALS. Detailed clinical assessments will be conducted at regular intervals throughout the study in order to achieve these objectives.
Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder that impairs motor neurons, with a life expectancy of 2 to 7 years after diagnosis. ALS manifests as 'spinal' when it primarily affects limbs, or 'bulbar' when it impairs speech and swallowing. The disease progressively weakens all skeletal muscles, causing respiratory issues and increased risk of lung infections due to ineffective coughing. Mechanical cough assistance via In-exsufflation therapy/ mechanical in-exsufflator devie (INEX/MI-E) applies positive and negative airway pressures non-invasively to improve coughing. However, MI-E may fail in some ALS patients due to airway collapse, often related to brainstem muscle dysfunction.Research by Andersen et al. in 2017 highlighted that during MI-E, ALS patients often experience adverse laryngeal movements, which can obstruct airways and reduce the therapy's effectiveness. To combat this, they suggested individualized MI-E settings to minimize airway collapse. Modern MI-E devices, such as the EOVE-70, offer adjustable positive expiratory pressure (PEP) between cycles to potentially enhance airway stability and coughing efficiency. The current study focuses on the impact of PEP during therapy pauses on the peak expiratory flow rate in ALS patients, which could lead to improved therapeutic outcomes.
In response to oxidative stress, cells activate the Nrf-2 pathway, which induces translation of its target genes and corresponding proteins involved in the antioxidant response. This explains the interest in the Nrf-2 pathway in the pathophysiology of Amyotrophic lateral sclerosis (ALS), supported by the results of several studies and the modulatory effect of TDP-43 on the Nrf-2 pathway. Since both TDP-43 and Nrf-2 proteins are present in the peripheral blood mononuclear cells (PBMC) of ALS patients and may be correlated with disease progression, the investigators wish to explore their relationship and their application in the clinic as potential blood biomarkers for ALS.
This study is a single-center, randomized, double-blind, placebo parallel-controlled, dose-escalation clinical study. The aim of this study was to evaluate the safety, tolerability, and preliminary effect of Aleeto in adult patients with ALS, and to provide an appropriate dose for the future clinical trial.
Neuralis is an innovative assistive technology designed for individuals with severe neuromuscular conditions, enabling wheelchair control through EEG signals. This study aims to assess the safety, feasibility, and efficacy of Neuralis in restoring mobility and independence. The device is a discreet EEG headset which specializes in decoding signals from visual cortex, allowing users to initiate precise wheelchair movements through focused attention. This research seeks to demonstrate Neuralis' potential in revolutionizing assistive technology by offering a non-invasive, user-friendly solution for individuals facing motor impairments, ultimately enhancing their quality of life.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease. Studies have shown the importance of weight loss at the time of diagnosis and during the progression of the disease. However, the pathophysiological mechanisms behind weight loss remain unknown. Identifying these mechanisms could make it possible to propose an effective therapeutic strategy against weight loss for ALS patients, which could improve their survival and quality of life. In this context, the investigators are proposing an innovative multidisciplinary project aimed at structuring a large Franco-German cohort to identify the markers associated with weight loss in ALS. Participants will undergo high quality standard care for ALS patients. In addition, participants will be asked to respond different questionnaires and blood samples will be taken for analysis to identify biological markers.
Phase II/III multicenter, randomized, double-blind, placebo-controlled trial on acetyl-L-carnitine (ALCAR) in subjects living with amyotrophic lateral sclerosis (ALS). Primary study aim: The clinical objective consists of assessing the efficacy of ALCAR (two different dosages will be tested: 1.5g/day and 3g/day) on the progression of functional disability (loss of self-sufficiency), as measured by the ALSFRS-R scale. Secondary study aims: 1. The effect of ALCAR treatment on different clinical aspects: functional decline as measured by ALSFRS-R total score; the decline of forced vital capacity (FVC); quality of life as measured by ALSAQ-40 scale; cognitive function as measured by Edinburgh Cognitive and Behavioural ALS Screen (ECAS) scale; survival (being alive and without tracheostomy). 2. To measure the effects of ALCAR treatment on disease biomarkers potentially involved in the drug's mechanisms of action. These include PGC-1 alpha, 3-nitrotyrosine (3-NT), acetyl cyclophilin A (acetyl-PPIA), neurofilament light chain (NFL), creatine kinase (CK), Musclin/osteocrin, MyomiRNA (MiR-206), Uric acid, Matrix metalloproteinase-9 (MMP-9), Monocyte Chemoattractant Protein-1 (MCP-1), 4-Hydroxynonenal (HNE). 3. The tolerability and safety of ALCAR treatment by identifying unexpected adverse events. Study population: 246 subjects will be enrolled on one Australian and ten Italian ALS sites. Inclusion criteria: subjects aged 18+ years with a diagnosis of ALS according to Gold Coast Criteria; disease duration <24 months; satisfactory bulbar and spinal function (self-sufficiency evaluated by a score 3+ on the ALSFRS-R for swallowing, cutting food and handling utensils, and walking); satisfactory respiratory function (FVC ≥80% of predicted); documented progression of symptoms as measured by the ALSFRS-R scale. Disease progression rate (DFS) must be>= 0.33. DFS =(48- ALSFRS-R at screening)/months from onset to screening, treatment with Riluzole in the last four weeks. Exclusion criteria: antecedent polio infection; other motor neuron disease; involvement of other systems possibly determining a functional impairment; other severe clinical conditions; unwillingness or inability to take riluzole; previous use of ALCAR for any reason; inability to understand and comply with the study requirements, and to give written informed consent personally or via their legally authorized representative. All eligible participants will be randomized to receive ALCAR (1,5 or 3 g/day) or placebo in addition to riluzole 50 mg b.i.d. Permuted block (with a block size of 6), 1:1:1 centralized randomization scheme will be used. The overall treatment duration will be 48 weeks. After enrolment, each participant will be followed up until death. Eligible subjects will be seen after 4, 12, 24, 36 and 48 weeks. At each visit, a general assessment will be made, including vital signs, body mass index (BMI), neurological examination (including quantitative and qualitative evaluation of the motor system), comorbidity, concomitant treatments and adverse events. Blood samples will be collected at baseline -Day 1 (randomization)-, 4, 12, 24, 36 and 48 weeks to test biomarkers. Functional disability will be assessed at each visit using the ALS-FRS-R scale. The respiratory function will be assessed using a spirometer to measure FVC before starting treatment (baseline visit) and at 4, 12, 24, 36 and 48 weeks. Cognitive function will be evaluated at baseline, weeks 24 and 48, using ECAS scale. Health-related quality of life, measured by the ALSAQ-40, will be tested at baseline, 24 and 48 weeks. Compliance will be tested by the local investigators, counting unused packages at each follow-up visit. Pre-planned statistical analyses will be done on Intention-to-treat and Per-protocol (PP) populations. The statistical plan will include descriptive statistics and a comparison of the proportions of self-sufficient participants at week 48 using the chi-square or Fisher's exact test for the primary endpoint. Secondary endpoints measured by numerical scores obtained from clinical scales will be analyzed using repeated measures mixed models, while biomarkers using repeated measures ANOVA. Time-to-event endpoints, such as survival and the probability of remaining self-sufficient over 48 weeks, will be analyzed with Kaplan-Meier curves. The number of adverse events and serious adverse events after 48 weeks will be compared between treatment arms.