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.
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
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
Parallel
Digoxin
DrugTaken orally once daily
Placebo
DrugMatched Placebo taken orally once daily
Resolution of nonalcoholic steatohepatitis (NASH) without worsening of fibrosis
Proportion of participants who achieve resolution of NASH (defined by the NASH Clinical research network \[CRN\] as a score of 0-1 for inflammation, 0 for hepatocyte ballooning, and any value for steatosis) with no worsening of fibrosis (yes/no).
Improvement in liver fibrosis without worsening of NASH
Proportion of participants with improvement in liver fibrosis by ≥ 1 stage with no worsening of NASH (yes/no). Worsening of NASH is defined as ≥ 1 increase in lobular inflammation or hepatocyte ballooning according to criteria by the NASH clinical research network (NASH CRN)
Improvement in NAS without worsening of fibrosis
Proportion of participants with improvement in nonalcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 2 with no worsening of fibrosis after 24 weeks (yes/no)
Change in enhanced liver fibrosis (ELF) score
Change in Enhanced Liver Fibrosis (ELF) score.
Change in alanine aminotransferase (ALT)
Change in serum alanine aminotransferase (ALT) concentration (pg/ml)
Click on the lead sponsor to view all of their trials.
Yale University
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator
