Amyotrophic Lateral SclerosisPhase 1NCT07204977
Acamprosate in C9orf72 Hexanucleotide Repeat Expansion Amyotrophic Lateral Sclerosis (ACALS)
A Phase 1 study testing Acamprosate calcium in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
- What is being tested?
- Acamprosate calcium
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Feb 2026to 30 Sep 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following inclusion criteria:
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- PT and PTT >1.2 times the upper limit of normal.
- Hemoglobin <10mg/dL.
- Positive Hepatitis B Surface Antigen and Hepatitis C Virus Antibody
- Participants who are unable to swallow tablets whole, as required by the administration guidelines. This includes individuals with any medical condition or physical limitation that impedes their ability to swallow solid dosage forms.
- Participants who are dependent on a gastrostomy tube for medication administration. Since acamprosate is in tablet form that cannot be crushed or altered, it is unsuitable for administration through a gastrostomy tube.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
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.
Read more
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.
Read the 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 predetermined time points during the study.
- Being tested
- Acamprosate calcium
- Keywords
- Amyotrophic Lateral Sclerosis, Clinical Trial, Acamprosate, C9ORF72
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease, Frontotemporal Dementia With Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acamprosate calciumDrug
tablet
| Study group | Role | What they receive |
|---|---|---|
| Intervention | Other | This is a single arm study, capturing the safety profile of acamprosate over the course of the study. Receives: Drug: Acamprosate calcium |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Six months
Secondary outcomes (1)
To investigate the clinical effects of acamprosate in patients with ALS and mutation in C9orf72.
Change in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score from baseline at predetermined time points during the study.
Measured: Six months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2025
- Study start2 Feb 2026
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Justin Y Kwan, M.D., Principal investigator, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07204977
- Sponsor's protocol ID
- 10002127
- Other IDs
- 002127-N
- Status last verified
- 29 Sep 2026
- First submitted
- 2 Oct 2025
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Acamprosate in C9orf72 Hexanucleotide Repeat Expansion Amyotrophic Lateral Sclerosis (ACALS)
- ClinicalTrials.gov ID
- NCT07204977
- Acronym / sponsor ID
- 10002127
- Keywords
- Amyotrophic Lateral Sclerosis, Clinical Trial, Acamprosate, C9ORF72
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- 2 Feb 2026 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2028 (estimated)
- First posted
- 3 Oct 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 predetermined time points during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Intervention | Other | Drug: Acamprosate calciumThis is a single arm study, capturing the safety profile of acamprosate over the course of the study. |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following inclusion criteria:
- 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.
Key exclusion criteria (20 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acamprosate calciumtablet | Drug | Intervention |
Primary outcome
Safety of acamprosate in patients with ALS and mutation in C9orf72.
Time frame: 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).
1 secondary outcome
To investigate the clinical effects of acamprosate in patients with ALS and mutation in C9orf72.
Time frame: Six months.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Justin Y Kwan, M.D. principal investigator
National Institute of Neurological Disorders and Stroke (NINDS)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Acamprosate calcium in people with Amyotrophic Lateral Sclerosis and Motor Neuron Disease, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carol H Hoffman ((301) 451-1229, carol.hoffman@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of acamprosate in patients with ALS and mutation in C9orf72. (time frame: Six months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.