Clinical Research Directory

A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS)

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group Phase II study to evaluate the efficacy and safety of VHB937 in participants with early-stage ALS (within 2 years of ALS symptoms onset). The study comprises a core double-blind (DB) 40-week treatment period followed by an open label extension (OLE).

Examining Interactions Between PALS and Caregivers

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 their caregivers. The question is, What are the effects of communicative interaction on verbal communication in people with ALS when they interact with their caregivers and does this change over time? Participants will read words and sentences while they are interacting with their caregivers.

Study of COYA 302 for the Treatment of ALS

The ALSTARS trial will be conducted across 20-25 sites in the US and Canada, and will evaluate the safety and efficacy of an investigational treatment called COYA 302 for adults with Amyotrophic Lateral Sclerosis (ALS). COYA 302 is an investigational and proprietary biologic combination therapy with a dual immunomodulatory mechanism of action intended to enhance the anti-inflammatory function of regulatory T cells (Tregs) and suppress the inflammation produced by activated monocytes and macrophages. It is comprised of low dose interleukin-2 (LD IL-2) and DRL\_AB (a biosimilar candidate for abatacept). Participants will be randomly assigned to receive one of 2 regimens of COYA 302 or placebo (an inactive substance) for 24-weeks in the double-blind (DB) period. Those who complete this part of the study may be eligible to receive one of the two regimens of COYA 302 for an additional 24 weeks in a blinded active extension phase (EXT). The study will assess changes in disease progression using established ALS clinical outcome measures, including the ALS Functional Rating Scale-Revised (ALSFRS-R), neurofilament (NfL), maximal inspiratory pressure (MIP), slow vital capacity (SVC), and neurological assessments. Additional objectives include evaluation of biomarkers and safety through routine clinical assessments and adverse event monitoring.

PHENOGENE-1A (Cromolyn) Treatment in Patients With Mild to Moderate ALS

The purpose of this study is to test the effects of PHENOGENE-1A, which is the treatment under investigation in this study. This research will investigate if PHENOGENE-1A can help people with ALS by measuring their function using the ALS Functional Rating Scale Revised (ALSFRS-R), measuring lung function using pulmonary function tests (PFTs), such as forced vital capacity (FVC), and measuring neuro-inflammatory biomarkers in the blood.

Do Video Recordings of Multidisciplinary Clinics Improve Quality of Life for People With ALS and Their Caregivers?

Amyotrophic lateral sclerosis (ALS) is a fatal, rare neurodegenerative disease affecting 30,000 people in the United States. The gold standard of care for people with ALS is multidisciplinary clinics (MDC). In these multidisciplinary clinics, which occur every 3 to 4 months, people with ALS see up to 12 different healthcare providers (e.g., speech therapy, physical therapy, the ALS doctor). These clinics can last from three to five hours, and across these three to five hours people with ALS and their caregivers receive a lot of information that is critical to the care and quality of life for people with ALS. However, this information can be difficult to remember given the large amount of information that is conveyed. The current standard for providing take-home information about the visit is to provide patients with a written after-visit summary and access to their doctor's notes about the visit, typically through the patient portal. This study tests whether providing participants with video recordings of their MDC visits improves their quality of life and the quality of life of their caregivers. The study will enroll 400 pairs of people with ALS and their caregivers from eight different sites in the United States. Half of the participants in the study will receive their after-visit summary notes (the NOTES condition) and the other half of the participants will receive both their summary notes, but will also receive video recordings of their MDC visits that they can watch on their own at home (the VIDEO condition). The study will last for 12 months, with participants receiving NOTES or VIDEO at each of their regularly-scheduled MDCs during the 12 months. The study will test whether caregiver and patient participants in the VIDEO condition experience better quality of life than those in the NOTES condition at 1 month, 6 months, and 12 months from study enrollment. The results of this study will help determine what is the most effective approach to communicating MDC information to people with ALS and their caregivers.

First in Human (FIH) Study of ALN-SOD in Adult Participants With Amyotrophic Lateral Sclerosis Associated With Mutation in the SOD1 Gene (SOD1-ALS)

This study is researching an experimental drug called ALN-SOD (called "study drug"). This study is focused on people with Amyotrophic Lateral Sclerosis (ALS) caused by a change in a gene called the Superoxide Dismutase-1 (SOD1) gene. This type of ALS is known as "SOD1-ALS". This is the first time that ALN-SOD will be given to people. The aim of the study is to see how safe and tolerable the study drug is. The study is looking at several other research questions, including: * The effect the study drug has on specific biomarkers, which are substances in the blood or in the fluid that surrounds the brain and spinal cord, known as Cerebrospinal Fluid (CSF) * How much study drug is in the blood and in the CSF, at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects) * What effects the study drug has on ALS symptoms

Impact of Robotic Glove Use on Quality of Life, Grip Strength and Fine Motor Control in ALS

The goal of this clinical trial is to determine the impact of robotic glove use on quality of life, grip strength and fine motor control in participants with Amyotrophic Lateral Sclerosis (ALS). This will provide valuable insights into how an assistive technology intervention can influence functional ability in daily tasks and enhance overall well-being in individuals impacted by ALS. Participants will attend 3 in-person clinic visits (BASE, 4 week and 8 week visit) and 2 Telehealth visits (occurring 24 hours after BASE and 4 week visit). The in-person clinic visits will include assessments by either a physical or occupational therapist, followed by assessments and scoring of grip strength, various fine motor strength assessments of affected hand, fine motor coordination assessment of the affected hand and various quality of life scales. The participant will be fitted and measured for the appropriately sized robotic glove. Once the fit is confirmed, both the participant and caregiver will receive education on how to don and doff the glove, power it on and off, and follow the study protocol. Once they demonstrate understanding and independence with these steps, the intervention will begin. The robotic glove intervention consists of either the participant or caregiver donning the glove and powering it on. A timer will be set for 20 minutes. The participant will sit comfortably at a table with their elbow supported on the table. The PI and/or member of the study team will be present throughout the 20 minute session to monitor for discomfort, fatigue or any additional patient reported symptoms. Once the time is complete, the robotic glove will be powered off and the glove removed. The participant and caregiver will be instructed to perform this one time daily, for 5 days per week for a total of 8 weeks. The PI and study team members will be available for any questions via iPhone or e-mail throughout this time period. The Telehealth visits will consist of synchronous video and audio via the Zoom application. The PI and/or study team members will monitor the set up, application and powering on of the Robotic Glove. The treatment of 20 minutes will be monitored and any questions the participant or caregiver have will be answered. This visit's goal is to ensure compliance and proper application of the robotic glove.

HEALEY ALS Platform Trial - Regimen I NUZ-001

The HEALEY ALS Platform Trial is a perpetual multi-center, multi-regimen clinical trial evaluating the safety and efficacy of investigational products for the treatment of ALS. Regimen I will evaluate the safety and efficacy of a single study drug, NUZ-001, in participants with ALS.

Usnoflast Neuromuscular Investigation for Treatment Efficacy in Amyotrophic Lateral Sclerosis

Usnoflast Neuromuscular Investigation for Treatment Efficacy in Amyotrophic Lateral Sclerosis

Retinal Imaging in Neurodegenerative Disease

This study aims to develop and evaluate biomarkers using non-invasive optical coherence tomography (OCT) and OCT angiography (OCTA) as well as ultra-widefield (UWF) fundus photography to assess the structure and function of the retinal and choroidal microvasculature and structure in persons with mild cognitive impairment (MCI) and Alzheimer's Disease (AD), Parkinson's Disease (PD), or other neurodegenerative disease, diseases as outlined.

Quantification of Hsp90 in the Human Brain

This study tests the radiolabeled molecule ("tracer"), \[¹¹C\]HSP990, using positron emission tomography (PET) imaging to assess whether it can be used to measure levels of Heat Shock Protein 90 (Hsp90). The protein Hsp90 plays an important role in how proteins in the brain fold into their three-dimensional structure and how this protein helps maintain cellular homeostasis. Since neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are characterized by disrupted three-dimensional protein folding resulting in protein aggregation, we also aim to measure Hsp90 levels in patients with these conditions. \[¹¹C\]HSP990 is a promising tracer for this purpose and has already been extensively tested in animal models with safe and favorable results. The investigator now aims to evaluate this tracer in the human brain in healthy volunteers as well as in patients with Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis. The investigator expects that Hsp90 protein levels will be present at reduced concentrations in patients, possibly in different brain regions depending on the distribution of the disease-causing proteins associated with these disorders. Since the discovery of the important role of Hsp90 in neurodegenerative diseases, several candidate drugs targeting Hsp90 have been developed in recent years. The imaging method used in this study may support the development of Hsp90-targeting medications by enabling measurement of Hsp90 levels in the brain and assessment of the effects of these drugs.

Healing ALS Registry Observational Study (HAROS)

This is a prospective, observational, online study of people diagnosed with ALS, MND or PLS referred to as HAROS (Healing ALS Registry Observational Study). Participants will enter information into an online ALS registry once per month, including their ALSFRS-R data, certain other symptoms, dietary intake, supplements, medications and other therapies, both conventional and integrative. Participants will also enter the hours spent on optional self-study and free online education. The investigators will assess the effectiveness of various therapies and education by measuring physical outcomes.

A Clinical Trial to Evaluate NB-4746 in Participants With Amyotrophic Lateral Sclerosis.

The purpose of this trial is to learn about the effects of NB-4746 compared with placebo in people with amyotrophic lateral sclerosis. The questions this trial aims to answer in comparing NB-4746 to placebo are: * What adverse events associated with taking NB-4746 are reported during this trial? (An adverse event is any sign or symptom that participants have during a trial. Adverse events may or may not be caused by treatments in the trial.) * How does NB-4746 move into, through, and out of the body of the participants? * What is the change in the level of neurofilament light (NfL) in the participants' blood? (NfL is a marker used to measure the extent of damage to the nerve cells.) This trial has 2 parts. The trial doctors will start Part A before starting Part B of the trial. Participants have an option to enter the open label extension after completing Part A or Part B. Part A: Participants will be randomly placed into 1 of the 3 groups. There are equal chances to be assigned to either group. Group 1: Participants will receive NB-4746 capsules at a low dose to take by mouth twice daily for 1 month. Group 2: Participants will receive NB-4746 capsules at a high dose to take by mouth twice daily for 1 month. Group 3: Participants will receive placebo capsules to take twice daily for approximately 1 month. Part B: Participants will be randomly placed into 1 of the 2 groups. There are equal chances to be assigned to either group. Group 1: Participants will receive NB-4746 capsules at a dose determined by Part A to take by mouth twice daily for 12 weeks. Group 2: Participants will receive placebo capsules to take twice daily for approximately 12 weeks. None of the participants, trial doctors, or trial staff will know which treatment the participants will receive during Part A or B. Some trials are done this way because knowing what treatment the participants receive can affect the results of the trial. Doing a trial this way helps to make sure that the results are looked at with fairness across all treatments. Open-Label Extension: Upon the completion of Part A or Part B, the doctor will verify the participant's willingness to continue receiving study treatment. This open label extension continues until each participant completes up to 1 year of treatment. The trial doctors will check participants' ALS and general health throughout the trial.

A Clinical Trial of Early Ventilation in Amyotrophic Lateral Sclerosis (EVENT ALS)

Amyotrophic lateral sclerosis (ALS) is a disease that causes weakness of the muscles of the body. The disease can eventually lead to severe breathing problems, which is the most common cause of death from ALS. The treatment for breathing is non-invasive ventilation (NIV). It is a machine that helps a person breathe by pushing air in and out of their lungs through a mask worn over the face. Research has shown that NIV can improve the quality of life and survival of someone with ALS. Unfortunately, NIV is not equally beneficial for everyone. The investigators do not yet know the best time or method for starting NIV in ALS. Europe and Canada allow starting NIV much earlier in ALS than the United States. Current recommendations for starting NIV are based on the opinion of experts rather than large research studies. Medical insurance companies will not cover NIV until significant breathing weakness occurs. After NIV is started, there is no evidence-based guidance on the best way to adjust NIV to benefit patients as much as possible. Some patients have difficulty tolerating NIV, but it is not clear how to identify these individuals ahead of time. The investigators have created a new prediction tool that can identify patients at high risk of breathing problems within the next 6 months. This may help the study team identify who is more likely to benefit from starting NIV early. The investigators have published a paper that shows that NIV helps people with ALS live longer. This paper also showed that patients get more benefit with use NIV for at least 4 hours per day. The investigators published another paper that measured a gas called carbon dioxide (CO2), which goes high if someone's breathing is weakened. This paper showed that patients with ALS may live longer when CO2 levels are lowered using NIV. The investigators also have data suggesting that certain characteristics may predict who is less likely to use NIV at least 4 hours per day. In this study, the investigators will collect pilot data on starting early NIV in individuals with ALS who do not yet meet insurance criteria for covering NIV. The research team will first use their previously published prediction tool to identify patient risk. Then, subjects would be randomized to start early NIV or to usual care. The usual care group would eventually start NIV as would occur if the participants were not in the study. The purpose of this study is to collect data to help the investigators plan a larger randomized clinical trial. This study has 4 objectives. First, the project aims to identify individuals who would benefit from earlier NIV. The research team will use the original prediction tool to identify risk of severe breathing problems within the next 6 months. Second, the project aims to show that it is feasible to start NIV early. Third, the project aims to gather data on the effect of randomization on symptoms, CO2 levels, and outcomes. Fourth, the project aims to identify traits that may make someone less likely to use NIV.

Lung Insufflation Capacity Training and Respiratory Function in Amyotrophic Lateral Sclerosis

The goal of this clinical trial is to learn whether lung insufflation capacity (LIC) training can help maintain respiratory function and prolong survival in people with amyotrophic lateral sclerosis (ALS). The main questions it aims to answer are: * Does early and continuous LIC training slow the decline in forced vital capacity (FVC)? * Does LIC training delay the need for tracheostomy or noninvasive ventilation (NIV)? This single-center study at the National Center of Neurology and Psychiatry (NCNP) in Japan will enroll 15 adults with ALS, diagnosed according to the El Escorial or Awaji criteria. Participants will: * Use the LIC Trainer device to perform lung insufflation training twice daily at home * Visit the clinic every 3 months for respiratory and functional assessments * Have lung tests, including FVC, LIC, maximum insufflation capacity (MIC), cough peak flow (CPF), and complete the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) There is no control group within this trial; researchers will compare results with matched historical controls from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database.

Translating Single-cell Vulnerability Into Novel ALS Biomarkers and Therapeutic Targets: Towards a Liquid Nerve Biopsy

The progress of ALS research and clinical practice is hampered by lack of effective biomarkers to monitor disease onset and progression. In response to this urgent need, we will integrate single-cell system biology approaches, histopathological and clinical data from precious human nerve biopsies collected from living ALS patients during the diagnostic workup and findings from innovative preclinical mouse models to unmask cell-specific molecular alterations that arise in the PNS tissue during the course of ALS pathology. This information will be used to select protein biomarkers of dysfunctional states associated with pre-manifest or early symptomatic stages of the disease, which will be further screened and validated in patient biofluids. Altogether, this project will lead to the discovery of novel, reliable and specific ALS biomarkers while providing insights into ALS mechanisms by leveraging an original "PNS perspective" on disease pathogenesis.

Investigating the Impact of Electrical Stimulation on Facial Pain, Jaw Movement and Oral Health in People With Motor Neuron Disease.

The goal of this clinical trial is to evaluate the impact of non-invasive electrical stimulation, when placed on the facial muscles can reduce facial pain and improve jaw mobility, and chewing in individuals with Amyotrophic Lateral Sclerosis (ALS) and Primary Lateral Sclerosis (PLS). The secondary goal is to evaluate the impact of non-invasive electrical stimulation on patient reported difficulty performing oral hygiene tasks in individuals with ALS and PLS. Participants will attend one in-person clinic visit and participate in one telephone interview 24 hours after the treatment. The clinic visit will include pre-intervention assessments, a single 30-minute treatment of electrical stimulation followed by post-intervention assessments. The assessments will include a self-rating of jaw and facial pain, a range of motion test where participants will be asked to open their jaw as wide and as far to the side as possible, and a chewing efficiency test using a saltine cracker. Twenty-four hours later, participants will receive a follow-up phone call to self-rate their facial pain and report any difficulty performing oral hygiene tasks. The treatment consists of a single 30-minute electrical stimulation session. Electrode pads will be placed on the participant's facial region, specifically over the masseter muscle belly and the TMJ area, while the participant is seated comfortably. The pads will be connected to an FDA-approved electrical stimulator, and the current will be adjusted to the participant's comfort level. Once set, the participant will remain seated for 30 minutes. At the end of the session, the stimulator will be turned off and the electrode pads removed.

The Safety, Tolerability and Preliminary Efficacy of Derived Motor Neuron Progenitor Cells (XS228CN) in Subjects With Amyotrophic Lateral Sclerosis

A Phase I Study to Assess the Safety, Tolerability and Preliminary Efficacy of Derived Motor Neuron Progenitor Cells (XS228CN) in Subjects with Amyotrophic Lateral Sclerosis

Resiliency Intervention for Patients With ALS and Their Care-Partners

The purpose of this study is to pilot a resiliency and coping intervention for persons recently diagnosed with Amyotrophic Lateral Sclerosis (ALS) and their primary informal caregivers. The data investigators gather in this study will be used to further refine our intervention.

Identification of Early Markers for ALS

Although several molecules have been proposed as biomarker candidates, a clinically established signature for an early or even premotor diagnosis of ALS is not available. Due to the already advanced, disease stage at the time of diagnosis as well as rapid disease progression, an early diagnosis is mandatory for efficacious disease-modifying therapies. In this project, the investigators will develop a clinical molecular fingerprint of PGMC that will provide insight into the molecular pathogenesis of ALS and allow earlier diagnosis.

Efficacy and Safety of Masitinib in Combination With SoC Versus Placebo in the Treatment of ALS Patients

The objective is to compare the efficacy and safety of masitinib in combination with riluzole versus matched placebo in combination with riluzole for the treatment of Amyotrophic Lateral Sclerosis (ALS).

Integrating Metabolism, Connectivity, and Mesoscale Imaging at Ultra-high Field to Decipher Mechanisms of Resilience and Neurodegeneration in Neurological Diseases and Healthy Aging

The MESO7 study is a prospective observational research project designed to investigate the mechanisms of resilience and neurodegeneration in neurological diseases and healthy aging. It leverages advanced multiparametric brain and spinal cord imaging at high (3T) and ultra-high magnetic fields (7T) to assess structural, functional, metabolic, and mesoscale changes in the central nervous system (CNS). Particular emphasis is placed on sodium (23Na-MRI) and phosphorus (31P-MRI) imaging, along with layer-dependent brain connectivity analysis. The primary objective is to evaluate the impact of neuronal energy failure, measured via sodium concentration, on functional and structural reorganization in both healthy individuals and patients with various neurological conditions. Directed brain network models will be constructed from MRI data to quantify the connectivity strength (in- and out-degree) of cortical nodes. These connectivity metrics will be correlated with sodium concentrations to assess energy failure and its role in network reorganization. Longitudinal follow-up over two years is planned for subgroups with clinically progressive diseases. Secondary objectives include decoding metabolic, microstructural, and functional signatures of successful aging at the laminar level; characterizing disease-specific patterns of cortical and spinal microstructure associated with physical and cognitive dysfunction; describing longitudinal mesoscale and metabolic changes; and generating representative normative imaging datasets for the neuroscience community. The study plans to enroll a total of 540 patients across 9 neurological conditions:Multiple Sclerosis (MS), Neuromyelitis Optica Spectrum Disorders (NMOSD), MOG Antibody Disease (MOGAD), Alzheimer's disease, Parkinson's disease, Amyotrophic Lateral Sclerosis (ALS), temporal and non-temporal epilepsy, and mild traumatic brain injury (mTBI),in addition to 160 age- and sex-matched healthy controls, totaling 700 participants. Imaging and clinical assessments will be performed at the CEMEREM center at Timone University Hospital, AP-HM, Marseille, France. Each participant will undergo multiparametric brain and spinal cord MRI, including DTI, BOLD, MP2RAGE, SWI, quantitative sodium and phosphorus imaging, and functional assessments including neuropsychological testing, visual and motor function tests. Disease-specific assessments such as OCT, evoked potentials, and disability scores (e.g., EDSS for MS) will also be included when appropriate. The study is expected to improve understanding of CNS adaptation mechanisms and support the development of more accurate diagnostic and prognostic tools for neurodegenerative diseases

Clinical Study of Regulatory T Cells (Tregs) in the Treatment of Neurodegenerative Diseases

An open, multi- center phase Ⅰ clinical study evaluating the safety and efficacy of autologous human polyclonal regulatory T cell injection (NP001 cell injection) in patients with Neurodegenerative diseases (ALS).

Dynamic Impact of NIV on Diaphragmatic Ultrasound in Patients With Amyotrophic Lateral Sclerosis

The goal of this pilot observational study is to learn about the dynamic impact of the non invasive ventilation on the diaphragm in patient with amyotrophic lateral sclerosis. The main question it aims to answer : can diaphragmatic ultrasound detect differences in diaphragmatic motion (diaphragmactic excursion and diaphragmatic thickening between spontaneous breathing and non-invasive ventilation ? Participants will receive diaphragmatic ultrasound assessments both under spontaneous breathing and during non-invasive ventilation on their day hospital evaluation for ventilatory support.