About this trial
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. This study will study the contribution of androgens to liver injury and progression in PCOS and mechanistic role of dysregulated lipid metabolism and visceral adiposity in this process. Such findings will provide the rationale for future efficacy studies evaluating selective androgen receptor (AR) antagonism for NASH in PCOS, or alternatively, the need to directly target visceral adiposity or lipid-specific pathways as part of a precision medicine approach to halt fibrosis progression in the nearly 5 million young women with PCOS and NAFLD in the U.S., who remain at increased risk for early onset and progressive liver disease.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Women aged 18-42 years with hyperandrogenic PCOS
NASH identified on liver biopsy or probable NASH on transient elastography- controlled attenuation parameter (TE-CAP) with cutoffs defined as CAP score ≥270 decibel/m and TE score > 7.0 kPA or alanine aminotransferase ≥40 U/L).
Disqualifiers
Uncontrolled diabetes
Alcohol consumption >2 drinks per day for at least 3 consecutive months over the previous 5 years
Other chronic liver disease (i.e. hepatitis B virus, hepatitis C virus, autoimmune hepatitis) or cirrhosis from any cause
Recent or planned upcoming weight reduction surgery within five years of diagnosis of biopsy-confirmed NASH
Trial design
Parallel
Treatments tested in this trial
Bicalutamide 50 mg
DrugBicalutamide capsules will be prepared from U.S. Pharmacopeia grade powder at a dose of 50 mg
Placebo
DrugMatching placebo capsules of the same color, mass, and appearance to the bicalutamide capsules will be filled using microcrystalline cellulose powder.
Treatment groups
Trial outcomes
Primary outcomes
Change in liver stiffness on Magnetic Resonance Elastography (MRE)
The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)
Secondary outcomes
Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF)
The investigators will assess for percent change in fat fraction by MRI-PDFF
Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI)
The investigators will assess for percent change in VAT as quantified by MRI
Change HOMA-IR (Homeostatic model assessment (HOMA) for insulin resistance (IR))
The investigators will assess change in continuous measures of HOMA-IR as insulin resistance is known to contribute to NASH progression
Change in the NAFLD Activity Score (NAS) on a scale from 0 (low activity) to 8 (high activity)
The investigators will assess for change in this histologic scoring system of NASH as a continuous measure among women willing to undergo end of treatment biopsy (not required).
Sponsors and contacts
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University of California, San Francisco
Lead sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborator