NCT03576755

Spironolactone Therapy In Young Women With NASH

Pilot Randomized Controlled Trial of Spironolactone in Young Women With Nonalcoholic Steatohepatitis (NASH)

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: University of California, San Francisco · Academic / Other
• Sex: Female
• Age: 18 Years – 45 Years
• Healthy volunteers: Not accepted

Summary

Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is projected to be the leading cause of cirrhosis in the United States (U.S.) within the next few years. Women are at disproportionate risk for NASH, with approximately 15 million U.S. women affected. There is an urgent need to understand risk factors for NASH and its progression in women, and sex hormones may provide a missing link. The investigator's preliminary data support a detrimental role of androgens, or "male sex hormones" on fatty liver in women but no studies have evaluated whether androgens are associated with liver inflammation and/or scarring from fatty liver (aka NASH). To better understand the mechanism by which androgens might promote NASH and/or metabolic co-factors that contribute to NASH, the investigators are conducting a pilot clinical trial to primarily assess the feasibility of using an androgen blocking medication, spironolactone, in women with NASH. Spironolactone was selected because it is has been commonly prescribed for decades with good safety profile and tolerability to treat symptoms of high androgens, like acne and hirsutism in young women. Though primarily a feasibility-focused study, the investigators also aim to explore the pathways by which blocking testosterone receptors might alter the biologic processes that promote NASH and its associated metabolic co-morbidities in women.

Detailed description

This is a single center, double-blind, placebo-controlled, randomized, (2:1) parallel group pilot clinical trial of spironolactone in women with biopsy-proven NASH receiving 6 or 12 months of spironolactone or placebo. 30 women are targeted for enrollment. Each participant will be administered a single dose of spironolactone or placebo once daily for a total of 6 or 12 months. In person evaluations will take place at Month 1, 3, 6, 9, and 12. There will be a telephone follow up visit within 3 months of end of treatment (up to Month 9 or 15). This is a pilot clinical trial that is largely feasibility focused. Study outcomes will include * Change in liver stiffness on Magnetic Resonance Elastography (MRE) * Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF) * Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI) * Change in NASH histology as assessed by the continuous NAFLD activity score (NAS), which measures different components of NASH on liver biopsy. * Biochemical endpoints: serum lipids \& HOMA-IR * Feasibility outcomes including Rates (and reasons) for the following: a) % women that decline/women contacted for study inclusion (i.e. need for a second liver biopsy, concern regarding randomization to placebo) b) % women enrolled/women screened (i.e. exclusion criteria too narrow), c) study dropout (i.e. medication side effects, too frequent study visits, and/or phlebotomy)

Conditions

• NASH - Nonalcoholic Steatohepatitis

Interventions

Type	Name	Description
DRUG	Spironolactone 100mg	Spironolactone capsules will be prepared from USP grade powder at a dose of 100 mg.
DRUG	Placebo oral capsule	Matching placebo capsules of the same color, mass, and appearance to the spironolactone capsules will be filled using microcrystalline cellulose powder.

Timeline

• Start date: 2019-01-09
• Primary completion: 2023-07-05
• Completion: 2023-07-05
• First posted: 2018-07-03
• Last updated: 2025-03-26
• Results posted: 2025-03-26

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study