Digoxin In NASH (CODIN)

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.

Timeline

Start

2025-06-05

Primary completion

2029-01

Completion

2029-01

Publications

• Background Jamshed F, Dashti F, Ouyang X, Mehal WZ, Banini BA. New uses for an old remedy: Digoxin as a potential treatment for steatohepatitis and other disorders. World J Gastroenterol. 2023 Mar 28;29(12):1824-1837. doi: 10.3748/wjg.v29.i12.1824.
• Background Dashti F, Jamshed F, Ouyang X, Mehal WZ, Banini BA. Digoxin as an emerging therapy in noncardiac diseases. Trends Pharmacol Sci. 2023 Apr;44(4):199-203. doi: 10.1016/j.tips.2022.10.002. Epub 2022 Nov 14.
• Background Agyapong G, Dashti F, Banini BA. Nonalcoholic liver disease: Epidemiology, risk factors, natural history, and management strategies. Ann N Y Acad Sci. 2023 Aug;1526(1):16-29. doi: 10.1111/nyas.15012. Epub 2023 Jul 3.
• Background Ilagan-Ying YC, Banini BA, Do A, Lam R, Lim JK. Screening, Diagnosis, and Staging of Non-Alcoholic Fatty Liver Disease (NAFLD): Application of Society Guidelines to Clinical Practice. Curr Gastroenterol Rep. 2023 Oct;25(10):213-224. doi: 10.1007/s11894-023-00883-8. Epub 2023 Sep 28.

Drugs

Indications