Digoxin In NASH (CODIN)

Phase 2

Not yet recruiting

• Conditions: NASH; NAFLD; MASH - Metabolic Dysfunction-Associated Steatohepatitis; Mash; MASLD; Fatty Liver Disease, Nonalcoholic; MASH With Fibrosis; Fatty Liver Disease
• Interventions: Drug: Digoxin; Drug: Placebo

• Registration Number: NCT06588699
• Lead Sponsor: Yale University

Brief 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.

Detailed 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 digoxin compared to placebo

Study Timeline

• Study First Submitted: 2024-09-06
• Study First Submitted QC: 2024-09-06
• Study First Posted: 2024-09-19
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-09
• Last Update Posted: 2025-04-13
• Study Start: 2025-04-30
• Primary Completion: 2029-01
• Study Completion: 2029-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 144

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Digoxin (titration-based)	Digoxin	Digoxin (titration-based) taken orally once daily. In this arm, the intervention will be administered dosed by weight and renal function using a well-studied digoxin nomogram.
Digoxin (weight-based)	Digoxin	Digoxin (weight-based) taken orally once daily. In the weight-based digoxin arm, the intervention will be oral digoxin 0.15mcg/kg/day.
Placebo	Placebo	Placebo, taken orally once daily

Primary Outcome Measures

Name	Time	Method
Resolution of nonalcoholic steatohepatitis (NASH) without worsening of fibrosis	24 weeks	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).

Secondary Outcome Measures

Name	Time	Method
Improvement in liver fibrosis without worsening of NASH	24 weeks	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	24 weeks	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	24 weeks	Change in Enhanced Liver Fibrosis (ELF) score.
Change in alanine aminotransferase (ALT)	24 weeks	Change in serum alanine aminotransferase (ALT) concentration (pg/ml)
Change in aspartate aminotransferase (AST)	24 weeks	Change in serum aspartate aminotransferase (AST) concentration (pg/ml)
Change in gamma glutamyl transferase (GGT)	24 weeks	Change in serum gamma glutamyl transferase (GGT) concentration (pg/ml)
Change in liver stiffness measure (LSM) and controlled attenuation parameter (CAP)	24 weeks	Change in liver stiffness measure (LSM) and controlled attenuation parameter (CAP) from baseline as measured by transient elastography.
Change in magnetic resonance imaging proton density fat fraction (MRI-PDFF)	24 weeks	Change in magnetic resonance imaging proton density fat fraction (MRI-PDFF)
Change in Magnetic resonance elastography (MRE)	24 weeks	Change from baseline in magnetic resonance elastography (MRE)

Trial Locations

Locations (2)

Yale New Haven Health; 🇺🇸 New Haven, Connecticut, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States