Trial of Oral Digoxin in Individuals With Amyotrophic Lateral Sclerosis (ALS)

NCT07047209 | Active Not Recruiting Phase 2 FDA Drug

• 1 other identifier: 2025P001103
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

ALS (Amyotrophic Lateral Sclerosis)

Keywords

ALS; Amyotrophic Lateral Sclerosis; Early ALS

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  From drug initiation through study completion, an average of 28 weeks

Secondary Outcomes (2)

• Biological Efficacy

  From enrollment to the end of study treatment at the Week 24 Visit

• CNS Penetrance

  From enrollment to end of study treatment at the Week 24 Visit

Other Outcomes (6)

• ALS Functional Rating Scale Revised (ALSFRS-R) total and sub-domain scores.

  From enrollment to the end of study treatment at the Week 24 Visit

• Slow vital capacity (SVC)

  From enrollment to the end of study treatment at the Week 24 Visit

• Quality of Life measure: ALSAQ-40 total score

  From enrollment to the end of study treatment at the Week 24 Visit

Study Arms (1)

Treatment Group

EXPERIMENTAL

Drug: Digoxin

Interventions

Digoxin DRUG

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.

Treatment Group

Eligibility Criteria

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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• \. 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).
• \. Presence of cognitive or mental health disorders impairing ability to provide informed consent for the study per Site investigator assessment.
• \. 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.
• \. If female, breastfeeding, pregnant, or of child-bearing potential and unwilling to use effective contraception for duration of the trial and after discontinuing treatment.
• \. 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.
• \. 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (3)

Nova Southeastern University

Davie, Florida, 33314, United States

Location

Northwestern Universsity

Chicago, Illinois, 60611, United States

Location

MGH

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Digoxin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Study Record Dates

• First Submitted: June 18, 2025
• First Posted: July 2, 2025
• Study Start: May 27, 2025
• Primary Completion: March 1, 2026
• Study Completion: April 1, 2026
• Last Updated: October 30, 2025

Record last verified: 2025-10

Locations

US (3)