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

Not Applicable

Recruiting

• Conditions: Amyotrophic Lateral Sclerosis; Motor Neuron Disease
• Interventions: Drug: Acamprosate calcium

• Registration Number: NCT07204977
• Lead Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)

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.

Detailed Description

Study Description:

This study will evaluate the safety and clinical effects of acamprosate in patients diagnosed with amyotrophic lateral sclerosis who have a hexanucleotide repeat expansion in the C9orf72 gene. A drug repurposing evaluation using genomic data from C9orf72 genetic mutation carriers showed that acamprosate may have a neuroprotective effect in this group of patients in silico and experiments. To examine the in vitro effect, iPSC derived motor neurons from ALS patients with C9orf72 repeat expansion were treated with acamprosate and reduced cell death was observed. Exploratory endpoints will include the effect of acamprosate on ALS disease progression.

Objectives:

Primary objective: To assess the safety of acamprosate in patients with ALS and mutation in C9orf72.

Secondary objective: To investigate the clinical effects of acamprosate in patients with ALS and mutation in C9orf72.

Exploratory objective: To investigate the clinical, laboratory, and neuroimaging effects of acamprosate in patients with ALS and mutation in C9orf72.

Endpoints:

Primary endpoint: Adverse events (AEs), Serious Adverse Events (SAEs), and laboratory abnormalities during treatment. Each AE will be categorized according to its severity, its relation to the study intervention, its frequency, and its outcome.

Secondary endpoint: The change in ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline at predetermined time points during the study.

Exploratory endpoint: The change ALS disease severity and quality of life scales, neurodegeneration biomarkers, and neuroimaging measures from baseline at predetermine time points during the study.

Study Timeline

• Status Verified: 2025-09-29
• Study First Submitted: 2025-10-02
• Study First Submitted QC: 2025-10-02
• Study First Posted: 2025-10-03
• Last Update Submitted: 2025-10-09
• Last Update Posted: 2025-10-10
• Study Start: 2025-10-15
• Primary Completion: 2027-09-30
• Study Completion: 2028-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Intervention	Acamprosate calcium	This is a single arm study, capturing the safety profile of acamprosate over the course of the study.

Primary Outcome Measures

Name	Time	Method
Safety of acamprosate in patients with ALS and mutation in C9orf72.	Six months	Incidence of adverse events and serious adverse events and abnormalities in laboratory tests (complete blood count, acute care panel, hepatic and mineral panel).

Secondary Outcome Measures

Name	Time	Method
To investigate the clinical effects of acamprosate in patients with ALS and mutation in C9orf72.	Six months.	Total score on the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)

Trial Locations

Locations (1)

National Institutes of Health Clinical Center; 🇺🇸 Bethesda, Maryland, United States