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

NCT07204977 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002127002127-N
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Keywords

Amyotrophic Lateral Sclerosis; Clinical Trial; Acamprosate; C9ORF72

Outcome Measures

Primary Outcomes (1)

• Safety of acamprosate in patients with ALS and mutation in C9orf72.

  Incidence of adverse events and serious adverse events and abnormalities in laboratory tests (complete blood count, acute care panel, hepatic and mineral panel).

  Six months

Secondary Outcomes (1)

• To investigate the clinical effects of acamprosate in patients with ALS and mutation in C9orf72.

  Six months.

Study Arms (1)

Intervention

OTHER

This is a single arm study, capturing the safety profile of acamprosate over the course of the study.

Drug: Acamprosate calcium

Interventions

Acamprosate calcium DRUG

tablet

Intervention

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years or older at the time of the screening visit.
• Able to provide informed consent and comply with study procedures and availability for the duration of the study. If a participant lacks capacity to give consent, a Legally Authorized Representative (LAR) will be authorized to give consent on behalf of the individual.
• Diagnosis of ALS (possible, probable, or definite according to the World Federation of Neurology El Escorial revised criteria or the Gold Coast Criteria) with or without mild cognitive impairment, mild behavioral impairment, or frontotemporal dementia (FTD).
• CLIA-certified genetic testing showing a pathogenic hexanucleotide repeat expansion in the C9orf72 gene.
• Symptom duration less than 2 years, or if greater than 2 years, disease progression at a rate that, in the judgement of the investigator, would allow for completion of the study.
• If taking riluzole, edaravone, or phenylbutyrate/TUDCA, the participant must be on a stable dose for at least 30 days prior to the screening visit, or have stopped taking riluzole, edaravone, or phenylbutyrate/TUDCA at least 30 days prior to the baseline visit.
• Participant must be competent to self-administer the medication as deemed by study team. Alternatively, participant must have a competent caregiver who can and will be responsible for administering the study drug. If there is no caregiver, another qualified individual must be available to administer the study drug.
• Participant has established care with a neurologist and will maintain this clinical care throughout the study.
• For females of reproductive potential: use of effective or highly effective contraception for at least one month prior to screening and agreement to use such a method during study participation and for an additional 8 weeks after the end of acamprosate administration. Participants of childbearing potential must have a negative pregnancy test at screening.
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Dependence on daytime mechanical ventilation (invasive or non-invasive, including Continuous Positive Airway Pressure (CPAP) or Bilevel Positive Airway Pressure (BiPAP) at the time of the screening visit.
• Participation in any other investigational drug trial or using investigational drug(s) (within 4 weeks prior to the Day 0 visit and thereafter).
• Participants must not become pregnant or breastfeed for the duration of the study. Participants of childbearing potential must have a negative pregnancy test at screening and be non-lactating.
• Men who are trying to become fathers or donate sperm.
• History of positive test or positive result at screening for HIV.
• History of severe sulfite allergy (i.e., anaphylaxis).
• Presence of any of the following clinical conditions at the time of screening:
• Active drug abuse or alcoholism.
• Unstable medical condition that, in the opinion of the investigators, makes participation unsafe.
• Renal impairment estimated glomerular filtration rate \<=60mL/min/1.73m\^2.
• Unstable psychiatric illness defined as psychosis or untreated major depression within 90 days of the screening visit.
• Safety Laboratory Criteria at the screening visit:
• Estimated glomerular filtration rate \<=60mL/min/1.73m\^2.
• Platelet concentration of \<100,000/microl.

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Frontotemporal Dementia With Motor Neuron Disease

Interventions

Acamprosate

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Taurine; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Justin Y Kwan, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2025
• First Posted: October 3, 2025
• Study Start: February 2, 2026
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: May 4, 2026

Record last verified: 2026-04-29

Locations

US (1)