Digoxin In NASH (CODIN)

Recruiting now · Phase 2 · Has a placebo group

Conditions studied: NASH, NAFLD, MASH - Metabolic Dysfunction-Associated Steatohepatitis, Mash, MASH With Fibrosis, MASLD, Fatty Liver Disease, Fatty Liver Disease, Nonalcoholic

In brief

Nonalcoholic steatohepatitis (NASH) is a severe subtype of nonalcoholic fatty liver disease (NAFLD) which affects 1 in 3 Americans. The mainstay of treatment for NASH, which was recently renamed metabolic associated steatohepatitis (MASH), involves lifestyle interventions to promote weight loss and to treat comorbidities such as hypertension, hyperlipidemia, and diabetes mellitus. There is thus, a substantial unmet need for pharmacological therapies that are effective for treatment of NASH, especially in those with fibrosis which is the main predictor of disease progression and mortality among NASH patients. The repurposing of presently available drugs would help expedite the search for agents effective in treating NASH. The cardiac glycoside digoxin is currently used in the management of heart failure and supraventricular tachyarrhythmias. The investigators and other groups have demonstrated that digoxin protects the liver from various forms of acute and chronic liver injury. The investigators preliminary data in healthy human subject indicate an immunomodulatory effect of low dose oral digoxin with no adverse side effects. This study proposes to demonstrate the clinical benefits of digoxin on NASH and on liver fibrosis, thus supporting the repurposing of digoxin as treatment for NASH.

Key facts

Study ID

NCT06588699

Run by

Yale University

People needed

144

Starts

2025-06-05

Expected to finish

2029-01-01

Last updated by the study team

2026-05-26

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Stable body weight (≤ 5% self-reported change in body weight) in the 30 days prior to screening
• Biopsy-confirmed non-alcoholic steatohepatitis (NASH) as defined by the NASH clinical research network (NASH CRN) histological scoring system, with non-alcoholic fatty liver disease score (NAS) ≥4 and with a score ≥1 for each of the three components (steatosis, hepatocellular ballooning, and lobular inflammation) on a liver biopsy performed within 6 months of screening
• Histological fibrosis stage 2 or 3 based on pathologist evaluation of a liver biopsy performed up to 6 months before screening
• Agrees to have a liver biopsy performed to assess baseline histology if one has not been performed up to 6 months before screening, and at 24 weeks after randomization Exclusion Criteria
• Liver-related:
• Documented causes of chronic liver disease other than NASH
• History or clinical evidence of cirrhosis or portal hypertension
• History of positive HBsAg, positive anti-HIV, positive HCV-RNA
• AST or ALT > 5 times upper limit of normal (ULN) at screening
• Total bilirubin > 1.5 mg/dL at screening unless conjugated bilirubin is < 1.5 × ULN
• International normalized ratio (INR) > 1.3 at screening
• Known or suspected alcohol use > 20 g/day for women or > 30 g/day for men
• Treatment initiation or dose adjustment of vitamin E, pioglitazone, GLP-1RA, or SGLT-2 inhibitors within 30 days of signing the informed consent or 30 days prior to liver biopsy
• Treatment initiation or anticipated treatment (>14 consecutive days) with medications known to affect steatosis (e.g., systemic corticosteroids, tamoxifen, valproic acid, methotrexate, tetracycline or amiodarone) within 30 days of signing the informed consent or 30 days prior to liver biopsy
• Cardiac related:
• Heart rate less than 60 bpm at screening (visit 1) or at baseline (visit 2)
• Current diagnosis of severe aortic valve disease
• History of Accessory arterio-ventricular pathway (e.g., Wolf-Parkinson-White syndrome)
• History of complete heart block or second degree arterio-ventricular block without pacemaker or implantable cardiac device
• Current diagnosis of permanent atrial fibrillation
• Any of the following within the previous 6 months of signing informed consent: myocardial infarction, percutaneous intervention, pacemaker/implantable cardiac device implantation, cardiac surgery, or stroke
• Current use of the following medications: inotropic drugs such as (dopamine, dobutamine, noradrenaline, milrinone), anti-arrhythmics (amiodarone, dofetilide, sotalol, dronedarone, digoxin), parathyroid hormone analog (teriparatide), sympathomimetics (epinephrine, norepinephrine, dopamine), neuromuscular blocking agents (succinylcholine), calcium supplement, nondihydropyridine calcium channel blockers, ivabradine, and disulfiram.
• Obesity related:
• Treatment initiation (in the 30 days prior to signing the informed consent or 30 days prior to liver biopsy) with orlistat, zonisamide, topiramate, phentermine, bupropion, and naltrexone alone or in combination or any other medication that could promote weight loss in the opinion of the investigator
• Participation (in the 30 days prior to signing the informed consent or 30 days prior to liver biopsy) in an organized diet-based weight reduction program (e.g., WeightWatchers, Optifast)

Where it is running

• Yale New Haven Health — New Haven, Connecticut, United States (enrolling)
• Yale New Haven Hospital — New Haven, Connecticut, United States (enrolling)

Full record on ClinicalTrials.gov

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