Clinical Trial of Oral Digoxin In NASH (CODIN)
Yale University
Summary
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.
Description
Prospective, randomized, double-blind, placebo-controlled, single center trial of digoxin in patients with nonalcoholic steatohepatitis (NASH). Primary objective: To compare the effect of digoxin oral, administered once daily (QD) either as titration-based or weight-based dose, versus placebo on histologic resolution of NASH Key secondary objectives: To investigate the effect of digoxin oral, administered once daily (QD) either as titration-based or weight-based dose, compared to placebo on histologic, imaging, and biochemical markers of NASH, and to assess the safety and tolerability of d…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria * 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 mon…
Interventions
- DrugDigoxin
Taken orally once daily
- DrugPlacebo
Matched Placebo taken orally once daily
Locations (2)
- Yale New Haven HealthNew Haven, Connecticut
- Yale New Haven HospitalNew Haven, Connecticut