ALS (Amyotrophic Lateral Sclerosis)Phase 2ACACIANCT07047209
Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS)
A Phase 2 study testing Digoxin in people with ALS (Amyotrophic Lateral Sclerosis), run by Massachusetts General Hospital at 3 sites in United States.
Trial summary
This clinical trial is being conducted to learn about safety and tolerability of digoxin in ALS individuals. Additionally, this trial aims to better understand if digoxin has an effect on slowing neurodegeneration in ALS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- ALS (Amyotrophic Lateral Sclerosis)
- What is being tested?
- Digoxin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 3 sitesUnited States
- Study dates
- 27 May 2025to 13 May 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to provide written informed consent.
- Adults >18 years of age with a diagnosis of symptomatic ALS as determined by an ALS neurologist, and meets either the revised El Escorial Criteria (clinically possible, probable, probable lab-supported, or definite) or the Gold Coast Criteria.
- Available or pending CLIA certified ALS genetic panel report.
- Less than or equal to 24-months since onset of weakness attributed to ALS.
- Vital capacity (VC) of > 65% predicted value for gender, height and age at screening.
- Clinically unremarkable Complete Blood Counts, including but not limited to Hemoglobin ≥ 9 g/dL, Platelets ≥ 150 x 109 cells/L.
Show all 13Show fewer
- No clinically significant abnormalities in the Comprehensive Metabolic Panel per site/sub-investigator's judgment, including but not limited to:
- Serum alanine aminotransferase or aspartate aminotransferase < 3× upper limit of normal, or serum total bilirubin <1.5× upper limit of normal
- Estimated GFR (eGFR) of > 30 mL/min/1.73m2
- Other clinically significant electrolyte and metabolic abnormalities
- Ability and willingness to complete all study procedures per the Site Investigator's clinical assessment.
- Negative pregnancy test within 7 days prior to first dose for women of child-bearing potential (WOCB), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally postmenopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months).
- Individuals enrolling in the C9orf72 cohort of the trial must have CLIA certified ALS gene panel demonstrating >31 repeats of C9orf72 hexanucleotide repeat expansion, deemed pathologic.
Who cannot join
- 1. Clinically significant unstable medical or surgical condition that would pose a risk to the participant's trial procedural participation or interfere with data collection, according to the Site Investigator's judgment (e.g., active infection requiring antibiotics).
- 2. Presence of cognitive or mental health disorders impairing ability to provide informed consent for the study per Site investigator assessment.
- 3. Active cancer or history of cancer, unless it was successfully treated for durable remission or cure more than 3 years ago. (Note that basal cell carcinoma, squamous cell carcinoma in situ, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies that have been curatively excised at any time previously and with no evidence of disease recurrence for at least 3 years are not exclusionary.) 4. Prior solid organ transplantation. 5. Concomitant use of investigational treatments for ALS within 5 half-lives or 30 days, whichever longer.
- 6. Screening 12-lead ECG showing QT interval corrected for rate (QTcF) > 470 msec for women and > 450 msec for men, absence of second degree or higher AV block or other clinically significant cardiac arrythmias.
- 7. If female, breastfeeding, pregnant, or of child-bearing potential and unwilling to use effective contraception for duration of the trial and after discontinuing treatment.
- 8. Serious cardiac condition within the last 6 months, such as uncontrolled arrhythmia, myocardial infarction, unstable angina, or heart disease defined by the New York Heart Association (NYHA) Class III or Class IV or hereditary long QT syndrome.
- 9. Exclusion criteria for Lumbar Punctures: active bleeding tendencies OR inability to withhold antiplatelets or anticoagulants safely as per institutional guidelines around LPs OR anatomical spine considerations making it unsafe or challenging for serial LPs OR allergy to local anesthesia used for procedure.
- 10. Clinically active cardiac disorders including sinus bradycardia (HR <40 bpm) or sinus tachycardia (HR>140 bpm), cardiac arrythmias [first-degree, second-degree (Wenckebach), or third-degree heart block; atrial tachycardia with block; AV dissociation; accelerated junctional (nodal) rhythm; unifocal or multiform ventricular premature contractions (especially bigeminy or trigeminy); ventricular tachycardia; and ventricular arrythmias]; Persistent or chronic atrial fibrillation that is not controlled using standard medications 11. Concomitant treatment with amiodarone at any dose or quinidine at a dose greater than 20 mg/day
Trial locations and contacts
3 sites in 1 country.
United States3 sites
MGH
Boston, Massachusetts, 02114
Northwestern Universsity
Chicago, Illinois, 60611
Nova Southeastern University
Davie, Florida, 33314
About this study
Official title: A Phase 2a Biomarker-Driven Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS) - The Acacia Trial, an ALS MyMatch Trial
This clinical trial is being conducted to learn about safety and tolerability of digoxin in ALS individuals. Additionally, this trial aims to better understand if digoxin has an effect on slowing neurodegeneration in ALS.
Read the detailed description
This is a single-arm, Phase 2a, open label, 24-week treatment trial evaluating standard clinical dosages of commercially available, FDA approved oral digoxin in up to 40 eligible ALS participants with early disease (<24 months from symptom onset). The trial will include two cohorts of eligible participants; Cohort 1 of approximately 30 sporadic/non-C9 ALS and Cohort 2 of approximately 10 C9orf72(+) ALS individuals.
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Being tested
- Digoxin
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Early ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DigoxinDrug
Digoxin tablets will be administered orally in a once daily dosage. Each tablet is scored and is of 125 mcg strength. Participants will take 1 tablet, two tablets or half a tablet depending on the dosing tier they are in during study participation.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group | Experimental | Not described Receives: Drug: Digoxin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety]
Safety: Defined as the occurrence of serious and non-serious treatment-emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical and laboratory values including digoxin trough levels, in ALS individuals treated with study treatment.
Measured: From drug initiation through study completion, an average of 28 weeks
Incidence of Completing Study Treatment [Tolerability]
Tolerability: Defined as percentage of ALS participants who complete the 24 weeks of study treatment, without study drug-attributed intolerable AEs that lead to early permanent drug discontinuation.
Measured: From drug initiation through study completion, an average of 28 weeks
Secondary outcomes (2)
Biological Efficacy
Biological Efficacy: Changes from baseline at week 24 in blood neurofilament light (NfL) levels following oral digoxin treatment.
Measured: From enrollment to the end of study treatment at the Week 24 Visit
CNS Penetrance
CNS Penetrance: Defined as CSF digoxin level measurement over 24 weeks of treatment.
Measured: From enrollment to end of study treatment at the Week 24 Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start27 May 2025
- Primary completion13 Apr 2026
- Study completion13 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for ALS (Amyotrophic Lateral Sclerosis)Studies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Suma Babu, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07047209
- Sponsor's protocol ID
- 2025P001103
- Acronym
- ACACIA
- Status last verified
- Jul 2026
- First submitted
- 18 Jun 2025
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a Biomarker-Driven Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS) - The Acacia Trial, an ALS MyMatch Trial
- ClinicalTrials.gov ID
- NCT07047209
- Acronym / sponsor ID
- ACACIA / 2025P001103
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Keywords
- ALS, Amyotrophic Lateral Sclerosis, Early ALS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- 27 May 2025 (actual)
- Primary completion
- 13 Apr 2026 (actual)
- Study completion
- 13 May 2026 (actual)
- First posted
- 2 Jul 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.
This clinical trial is being conducted to learn about safety and tolerability of digoxin in ALS individuals. Additionally, this trial aims to better understand if digoxin has an effect on slowing neurodegeneration in ALS.
Detailed description
This is a single-arm, Phase 2a, open label, 24-week treatment trial evaluating standard clinical dosages of commercially available, FDA approved oral digoxin in up to 40 eligible ALS participants with early disease (<24 months from symptom onset). The trial will include two cohorts of eligible participants; Cohort 1 of approximately 30 sporadic/non-C9 ALS and Cohort 2 of approximately 10 C9orf72(+) ALS individuals.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment Group | Experimental | Drug: Digoxin |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Ability to provide written informed consent.
- Adults >18 years of age with a diagnosis of symptomatic ALS as determined by an ALS neurologist, and meets either the revised El Escorial Criteria (clinically possible, probable, probable lab-supported, or definite) or the Gold Coast Criteria.
- Available or pending CLIA certified ALS genetic panel report.
- Less than or equal to 24-months since onset of weakness attributed to ALS.
- Vital capacity (VC) of > 65% predicted value for gender, height and age at screening.
Key exclusion criteria (8 listed)
- 1. Clinically significant unstable medical or surgical condition that would pose a risk to the participant's trial procedural participation or interfere with data collection, according to the Site Investigator's judgment (e.g., active infection requiring antibiotics).
- 2. Presence of cognitive or mental health disorders impairing ability to provide informed consent for the study per Site investigator assessment.
- 3. Active cancer or history of cancer, unless it was successfully treated for durable remission or cure more than 3 years ago. (Note that basal cell carcinoma, squamous cell carcinoma in situ, cervical carcinoma in situ, prostatic carcinoma in situ, or other malignancies that have been curatively excised at any time previously and with no evidence of disease recurrence for at least 3 years are not exclusionary.) 4. Prior solid organ transplantation. 5. Concomitant use of investigational treatments for ALS within 5 half-lives or 30 days, whichever longer.
- 6. Screening 12-lead ECG showing QT interval corrected for rate (QTcF) > 470 msec for women and > 450 msec for men, absence of second degree or higher AV block or other clinically significant cardiac arrythmias.
- 7. If female, breastfeeding, pregnant, or of child-bearing potential and unwilling to use effective contraception for duration of the trial and after discontinuing treatment.
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 |
|---|---|---|
| DigoxinDigoxin tablets will be administered orally in a once daily dosage. Each tablet is scored and is of 125 mcg strength. Participants will take 1 tablet, two tablets or half a tablet depending on the dosing tier they are in during study participation. | Drug | Treatment Group |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety]
Time frame: From drug initiation through study completion, an average of 28 weeks
Safety: Defined as the occurrence of serious and non-serious treatment-emergent adverse events (TEAEs) and clinically significant treatment-emergent abnormalities in clinical and laboratory values including digoxin trough levels, in ALS individuals treated with study treatment.
Incidence of Completing Study Treatment [Tolerability]
Time frame: From drug initiation through study completion, an average of 28 weeks
Tolerability: Defined as percentage of ALS participants who complete the 24 weeks of study treatment, without study drug-attributed intolerable AEs that lead to early permanent drug discontinuation.
2 secondary outcomes
Biological Efficacy
Time frame: From enrollment to the end of study treatment at the Week 24 Visit
CNS Penetrance
Time frame: From enrollment to end of study treatment at the Week 24 Visit
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
Related trials for ALS (Amyotrophic Lateral Sclerosis)
RecruitingPhase 1/2
Study is to Assess the Safety and Tolerability of VTx-002 in Participants With ALS
Amyotrophic Lateral Sclerosis
Not yet recruiting
A Study on the Addition of Alsum30 for the Treatment of Amyotrophic Lateral Sclerosis
Amyotrophic Lateral Sclerosis (ALS), Bacillus Coagulans
Active, not recruiting
Functional Outcomes and Control Using Synchron BCI - Australia
Neurologic Disorder, Neurologic Diseases
Not yet recruitingPhase 1
Safety, Tolerability, and Pharmacodynamic Exploration of Orelabrutinib in Patients With Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic Lateral Sclerosis (ALS)
Recruiting
Clinical Outcome Assessment for AT & BCI
Spinal Cord Injury, ALS (Amyotrophic Lateral Sclerosis)
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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Digoxin in people with ALS (Amyotrophic Lateral Sclerosis), run by Massachusetts General Hospital at 3 sites 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 13 inclusion and 8 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: finished, as of the sponsor's last update on 30 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety] (time frame: From drug initiation through study completion, an average of 28 weeks). The study lists 2 primary outcomes in all. 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 30 Jul 2026.