Clinical Research Directory

Acamprosate in C9orf72 Hexanucleotide Repeat Expansion Amyotrophic Lateral Sclerosis (ACALS)

Background: Amyotrophic lateral sclerosis (ALS) is a disorder that damages nerve cells in the brain and spinal cord. It can cause muscle weakness, paralysis, and loss of movement. The symptoms grow worse over time. Half of all people with ALS live only 3 to 5 years after diagnosis. Current drug treatments can slow the progress of the disease, but they cannot stop or reverse it. Objective: To test a study drug (acamprosate) in people with ALS with a mutation in the C9orf72 gene. Eligibility: People aged 18 years and older with ALS. They must have a mutation in the C9orf72 gene. Design: Participants will have 13 visits over 32 weeks. Five visits will be at the clinic, and 8 visits will be by phone. Participants will have a baseline visit of up to 3 days. They will have a physical exam with blood tests. They will have imaging scans and tests of their breathing ability. Their memory, thinking, and behavior will be assessed. They will have a neurologic exam to check their reflexes, strength, balance, eyes, and coordination. They will complete questionnaires about their daily life. They will have a lumbar puncture to collect fluid from the area around the spinal cord. Acamprosate is a pill taken by mouth. Participants will take 2 pills by mouth 3 times a day with meals for 24 weeks. They will record their doses and any missed doses in a diary. Baseline tests will be repeated during follow-up clinic visits. These tests may be spread out over 3 days. During phone visits, participants will talk about how they are doing. They will review their diary with researchers.

Investigating Complex Neurodegenerative Disorders Related to Amyotrophic Lateral Sclerosis and Frontotemporal Dementia

Background: Neurodegenerative disorders can lead to problems in movement or memory. Some can cause abnormal proteins to build up in brain cells. Researchers want to understand whether these diseases have related causes or risk factors. Objective: To test people with movement or thinking and memory problems to see if they are eligible for research studies. Eligibility: People ages 18 and older with a neurodegenerative disorder associated with accumulation of TDP-43 or Tau proteins Design: Participants will have a screening visit. This may take place over 2-3 days. Tests include: Medical history Physical exam Questions about behavior and mood Tests of memory, attention, concentration, and thinking Movement measurement. The speed at which participants can stand up from a chair, tap their finger and foot, and walk a short distance will be measured. Some movements will be videotaped. They will be videotaped while they speak and read a paragraph. Blood tests. This might include genetic testing. Lung and breathing tests MRI. They will lie on a table that slides into a cylinder that takes pictures of the body. Some participants will get a dye through IV. Electromyography. A thin needle will be inserted into the muscles to measure electrical signals. Nerve tests. Small electrodes on the skin record muscle and nerve activity. A small piece of skin may be removed. A skin or blood sample may be taken to create stem cells. Optional lumbar puncture. A needle will be inserted into the space between the bones of the back to collect fluid. If participants are not eligible for current studies, they may be contacted in the future. ...

A Study to Investigate the Safety and Pharmacodynamics of a Single Intrathecal Injection (IT) of INS1202 in Participants With Amyotrophic Lateral Sclerosis (ALS)

The primary objective of this dose-finding study is to evaluate the safety, tolerability and pharmacodynamics of single dose of INS1202 via IT administration in participants ≥ 18 to \<80 years of age with ALS who carry superoxide dismutase type 1 (SOD1) mutations or harbor no known ALS-related genetic mutation.

Research of Traditional Chinese Medicine Oral Preparation of C. Cicadae in the Treatment of ALS Patients With Elevated Plasma Sphingolipids

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons, leading to progressive muscle weakness and functional decline. This study is designed as a randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of an oral preparation of C. cicadae in patients with sporadic ALS and elevated plasma sphingolipid (SL) levels. Efficacy will be assessed primarily by changes in the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score and plasma SL levels.Participants who meet the eligibility criteria and provide written informed consent will be randomly assigned in a 1:1 ratio to either the C. cicadae treatment group or the placebo group. The treatment group will receive oral C. cicadae at a dose of 0.1 g/kg/day (dry weight), administered in three divided doses per day. The placebo group will receive a matched placebo with a similar appearance and odor, administered according to the same schedule. A total of approximately 84 participants will be enrolled. The intervention period will be 6 months, and participants will be followed for a total of 9 months.

Genetic Study of Amyotrophic Lateral Sclerosis in Norway

The purpose of this study is to explore the genetic causes relevant for ALS development in Norway.

A Study Evaluating the Safety and Tolerability of QRL-201 in ALS

The primary objective of this study is to determine the safety and tolerability of multiple doses of QRL-201 in people living with ALS

HEALEY ALS Platform Trial - Master Protocol

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.

Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS

PIONEER-ALS is a Phase 1/2, multicenter, open-label, ascending dose, uncontrolled, first-in-human study that will evaluate the safety, tolerability and effects on clinical and biomarker endpoints of intracisternal administration of Vtx-002 in participants with Amyotrophic Lateral Sclerosis (ALS). Two escalating dose (low dose and high dose) cohorts are planned. The duration of the study will be a maximum of 5 years and 5 weeks (265 weeks) for each participant. The screening period may last up to 5 weeks to complete screening procedures.

A Substudy of LY4256984 in Participants With Sporadic Amyotrophic Lateral Sclerosis

The main purpose of this study is to assess the long-term safety and tolerability of LY4256984 in participants with Amyotrophic Lateral Sclerosis (ALS). This study is a long-term extension of study J6I-MC-OWAA (NCT07100119) and is part of the OLMP (NCT07571200) master protocol that will last approximately 96 weeks.

Platform Trial to Assess the Efficacy of Multiple Drugs in Amyotrophic Lateral Sclerosis (ALS)

The objective of this phase III, placebo-controlled platform study is to investigate the efficacy of drugs for patients with ALS (Amyotrophic lateral sclerosis).

Breathing With Amyotrophic Lateral Sclerosis

The study aims to evaluate the effect of mechanical insufflator-exsufflator on the respiratory functions of Amyotrophic Lateral Sclerosis (ALS) patients evaluated via peak expiratory flow on cough (PEFC) measurements. The evolution of their PEFC is monitored to see if the curative management can have a positive impact on the latter.

Multicenter ALS Imaging Study

This is a multi-site study of ALS participants and healthy controls who will undergo brain and cervical spine MRIs and NfL blood testing at up-to 4 time points over the course of a year. The primary goal is to identify objective biomarkers of disease progression that are biologically relevant, linearly progressive, and sensitive to change.

Novel MRI Biomarkers for Monitoring Disease Progression in ALS

Routine MRI is normal in motor neuron diseases such as ALS. However, advanced MRI techniques can provide an objective measure of degeneration (a "biomarker") by examining brain structure, wiring, chemistry, and function. We will develop and evaluate novel MRI techniques that could improve our understanding of ALS and provide a means to diagnose it sooner and monitor its progression. Importantly, we expect these techniques to improve how new drugs are tested, which may lead to the more rapid discovery of a treatment for ALS. Each participant will have 3 MRI scans over a period of 8 months, along with neurological and cognitive evaluations. Study visits will take 2 - 3 hours. MRI is a safe technique that does not involve radiation.

Alter-Ego as an Assistive Robotic Device.

The ALTER-EGO study is a monocentric, observational clinical investigation designed to evaluate the safety, usability, and feasibility of the humanoid robotic platform Alter-Ego as an assistive device in hospital and simulated home-care settings. The system is intended to support healthcare and rehabilitation professionals in the management of patients with Amyotrophic Lateral Sclerosis (ALS). Alter-Ego is an anthropomorphic, wheeled, self-balancing social robot equipped with compliant robotic arms and SoftHand synergistic grippers. It operates in teleoperated, semi-autonomous, or fully autonomous modes and integrates advanced navigation, mapping, object manipulation, and natural language processing capabilities. The robot is not classified as a medical device under EU Regulation 2017/745, as it does not perform diagnostic or therapeutic functions, but provides logistical, communicative, and organizational support. The study is conducted at ICS Maugeri IRCCS (Milan Camaldoli). Participants include healthcare professionals (physicians, nurses, physiotherapists, occupational therapists, speech therapists, and healthcare assistants) and up to 40 hospitalized ALS patients. Patients are not direct operators of the robot but provide experiential feedback. A total of 40 experiments are organized into four clusters: Cluster 1 - Telemedicine (Teleoperated or Semi-Autonomous Mode) Within a simulated home-care environment, Alter-Ego supports remote clinical and rehabilitation activities through four specific tasks: Simulated Remote Medical Visit (First Home Transition): A physician conducts a tele-visit via the robot, asking health-related questions, performing visual neurological assessments using cameras and microphones, requesting specific motor tasks, and reviewing vital parameters from home monitoring devices. This task addresses the need for expert supervision during early discharge phases. Assistive Device Training: A physiotherapist and nurse remotely verify and guide the correct use of assistive devices such as non-invasive ventilation systems, PEG, or patient lifters, providing practical instructions to patients and caregivers. Home Environment Assessment: An occupational therapist uses the robot in semi-autonomous mode to map the domestic environment and, in tele-guided mode, visually inspect spaces to identify architectural barriers and optimize assistive device placement. Telerehabilitation: Physiotherapists and speech therapists use the robot's audio-video interface and display to conduct remote rehabilitation sessions and functional evaluations, providing visual and verbal feedback. Cluster 2 - Delivery Services (Autonomous Mode) The robot autonomously transports small items within the hospital ward, including medical records, blood collection kits, rehabilitation tools, and small food or beverage packages. Cluster 3 - Guidance and Welcome Assistance (Autonomous Mode) Alter-Ego presents ward service information to newly admitted patients and provides personalized daily reminders regarding scheduled rehabilitation activities. Cluster 4 - Monitoring (Autonomous Mode) The robot administers the Visual Analog Scale (VAS) for pain assessment and includes an exploratory function for detecting vocal distress keywords (e.g., "pain," "help," "thirst") using AI-based speech recognition, alerting staff when necessary. Primary endpoints include usability and feasibility (System Usability Scale - SUS; Questionnaire for User Interaction Satisfaction - QUIS; NASA Raw Task Load Index - NASA-RTLX) and safety assessment through systematic recording of adverse events. Secondary outcomes include healthcare professionals' satisfaction with autonomous robot performance, patient satisfaction (Likert scales), and psychosocial impact on professionals (selected PIADS items). The ALTER-EGO study aims to determine whether an anthropomorphic robotic platform can safely and effectively support multidisciplinary ALS care, improve workflow efficiency, and enhance patient-centered assistance in both hospital and transitional home-care settings.

A Master Protocol (OLMP): A Study of LY4256984 in Participants With Amyotrophic Lateral Sclerosis (ALS)

Study OLMP is a master protocol that will support a collection of individual sub studies that share key design components. Participants from the originator study OWAA (NCT07100119) will be assigned to the appropriate study treatment group. The studies aim to evaluate the safety and tolerability of different treatments in participants with Amyotrophic Lateral Sclerosis (ALS) that will last at least 96 weeks.

IC14 for Rapidly Progressive Amyotrophic Lateral Sclerosis (ALS)

Patients with rapidly progressive ALS will be assigned to IC14 intravenously on Day 1-4. This 4-day course will be repeated on Days 8-11. Patients will all undergo MR-PET scans at two time points: before treatment onset and after the last treatment cycle. This scan will measure areas of ALS disease activity and assess response to IC14 treatment. MR-PET scans will be compared to historical controls.

Study of Predictive Factors of Progression of Motor Neurone Disease

Amyotrophic lateral sclerosis (ALS) is a complex polymorph and devastating neurodegenerative disease. Although the pathophysiological mechanisms underlying the development of ALS remain to be fully elucidated, there have been significant advances in the understanding of ALS pathogenesis, with evidence emerging of a complex interaction between genetic factors and dysfunction of vital molecular pathways. However, the numerous randomized clinical trials (RCT) for ALS have failed to generate improved drug treatments. Biomarkers able to bring prognostic value and to distinguish the different endophenotypes of this polymorphic disease could help to better select clusters of patients in order to improve the RCT outcomes. However, little progress has been made in the development of viable diagnostic, prognostic and monitoring markers. This could be explained by common shortcomings, such as relatively small sample sizes, statistically underpowered study designs, lack of disease controls and poorly characterized patient cohorts. It is yet crucial that the investigators further develop and validate ALS biomarkers and incorporate these biomarkers into the drug development pipeline for ALS. 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). This is a prospective observational multicentric French study of a cohort of 1000 ALS patients. This large multimodal database will be open for international fruitful scientific collaborations.

TP04HN106 in the Treatment of Patients With Amyotrophic Lateral Sclerosis

This trial adopts a multicenter, randomized, double-blind, placebo-controlled parallel design. This experiment is divided into two groups: the experimental drug group and the placebo group. Successful participants will be randomly assigned to the two groups, with an expected enrollment of 60 participants. There will be 30 participants in the experimental drug group and 30 participants in the placebo group. During the treatment period, the experimental drug group received intravenous injections of 0.5mL/kg TP04HN106 each time; The placebo group received intravenous injections of 0.5mL/kg of saline each time. During the extension period, all subjects received intravenous injection of 0.5mL/kg TP04HN106. In the experiment, all subjects received Liraglutide tablets as the standard baseline treatment. The subjects who were successfully screened in the experiment were enrolled in sequence, and the safety, tolerability, efficacy, and pharmacokinetic characteristics of the experimental drug were evaluated after administration. The entire trial includes a screening period of 1 week, a treatment period of 12 weeks (including 3 treatment cycles, each treatment cycle of 4 weeks), an extension period of 12 weeks (including 3 treatment cycles, each treatment cycle of 4 weeks), and a follow-up period of 4 weeks. In addition, some subjects underwent a 1-week single dose PK study before the start of the treatment period; In addition, during the first treatment cycle of the treatment period, some subjects were selected for multiple dosing PK studies. We plan to conduct a single dose PK study among 12 subjects, with 6 subjects in the experimental group and 6 subjects in the control group; Multiple dose PK studies were conducted among 12 subjects, with 6 subjects in the experimental group and 6 sujects in the control group. It is not allowed for the same subject to participate in both single dose and multiple dose PK studies simultaneously. The 1st to 12th subjects planned to be enrolled in the trial will undergo a single dose PK study. After the first dose, venous blood will be collected from the 12 subjects according to the blood sample collection requirements, and their PK characteristics will be evaluated. The observation period for single dose administration is one week. After completing the final blood sample collection and safety assessment, the subjects enter the treatment period, extension period, and follow-up period. The 13th to 24th subjects planned to be enrolled in the trial will undergo multiple dose PK studies. These 12 subjects will have their venous blood collected according to the blood sample collection requirements during the first treatment cycle of the treatment period, and their PK characteristics will be evaluated. After completing the treatment period, the subjects will enter the extension period and follow-up period.

Efficacy and Tolerability of Beta Hydroxybutyrate Ester in Patients With Amyotrophic Lateral Sclerosis (ALS)

Weight loss is a known negative prognostic factor in amyotrophic lateral sclerosis (ALS). One potential mechanism of weight loss in ALS is a disturbance of the mitochondrial complex I which causes an energy deficit in affected cells. Over the last years, various interventional studies targeting the energy deficit in ALS yielded promising results; however,it is still unclear which kind of nutrition or nutritional supplement is most beneficial. Ketone bodies represent a logical therapeutic option in ALS as ketone bodies are an extremely high-energetic substrate which yields the double amount of adenosine triphosphate (ATP) per mole compared to glucose. The human liver is able to synthesize ketone bodies (beta-hydroxybutyrate, acetone, and aceto-acetate) from fat in times of glucose shortage, for example after a prolonged period of fasting. This metabolic shift is the underlying principle of the ketogenic diet, a carbohydrate-free, fat-rich diet which has been successfully tested in other neurodegenerative diseases such as Alzheimer's and Parkinson's disease. In the ALS mouse model, a ketogenic diet was associated with a slower decline of motor function. However, a ketogenic diet is difficult to implement in ALS as it requires a long-term change of eating habits, which is difficult to achieve due to progressive dysphagia, fast worsening of general condition, and limited survival. Therefore, the direct administration of ketone bodies yields a more realistic alternative in ALS as it is easy to apply and allows to maintain the usual eating habits. In this study, we hypothesize that the administration of 3 x 10 g beta hydroxybutyrate ester per day (in addition to normal food intake and the standard medication of 2 x 50 mg riluzole) slows down disease progression as measured by neurofilament light chains (NfL) in serum after 6 months compared to placebo. Power calculation relies on the results of the lipids and calories for ALS (LIPCAL-ALS) study which tested the effect of a high-caloric fatty nutritional supplement in ALS. The study revealed that NfL serum values declined significantly in the intervention group while remaining stable in the placebo group over the course of the study. Assuming a similar effect size for ketone bodies, we calculated that 76 patients had to be included in the current trial.

Ultra-high-caloric, Fatty Diet in ALS

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).

Evaluation the Efficacy and Safety of Mutiple Lenzumestrocel (Neuronata-R® Inj.) Treatment in Patients With ALS

ALSUMMIT is a double-blind, randomized, placebo-controlled, multi-center, parallel, phase III clinical trial to evaluate and confirm the efficacy and long-term safety of repeated Lenzumestrocel (Neuronata-R® inj.) treatment.

The National Amyotrophic Lateral Sclerosis Registry

The purpose of this registry is to (A) better describe the incidence and prevalence of Amyotrophic Lateral Sclerosis (ALS) in the United States;(B) examine appropriate factors, such as environmental and occupational, that may be associated with the disease; (C) better outline key demographic factors (such as age, race or ethnicity, gender, and family history of individuals who are diagnosed with the disease) associated with the disease; and (D) better examine the connection between ALS and other motor neuron disorders that can be confused with ALS, misdiagnosed as ALS, and in some cases progress to ALS.

A Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of Prosetin in Healthy Volunteers and Participants With ALS

The primary purpose of this study is to evaluate the safety and tolerability of prosetin in healthy volunteers and participants with ALS.

Pridopidine Phase 3 Study to Evaluate Efficacy and Safety in ALS

The goal of this clinical trial is to learn if the drug pridopidine works to treat amyotrophic lateral sclerosis in adults. It will also help to learn about the safety of pridopidine. The main question it aims to answer is: Does pridopidine slow disease progression of ALS? Researchers will compare pridopidine to a placebo (a look-alike substance that contains no drug) to see if pridopidine works to treat ALS. Participants will: Take pridopidine or a placebo by mouth every day for 48 weeks. Afterwards, all participants will take pridopidine for another 48 weeks. Visit the clinic once every 1-3 months for checkups and tests