RECRUITINGPhase 1INTERVENTIONAL

Bicalutamide Therapy in Young Women With NAFLD and PCOS

Pilot Trial of Bicalutamide Versus Placebo in Reproductive-Aged Women With Nonalcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovary Syndrome (PCOS)

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.

Who May Be Eligible (Plain English)

Who May Qualify: - 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). Who Should NOT Join This Trial: - 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 - HIV infection - Drugs associated with fatty liver (i.e. amiodarone, methotrexate, systemic glucocorticoids, tamoxifen, anabolic steroids, valproic acid) for more than 4 weeks prior to baseline or during study - Recent, current, or planned upcoming pregnancy or current perimenopausal status - Renal impairment (glomerular filtration rate \<45 ml/min/1.73m or potassium levels \> 5.0 mmol/L) - Androgen receptor antagonist use (i.e. spironolactone or flutamide) for more than 3 months within one year prior to baseline Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * 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). Exclusion Criteria: * 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 * HIV infection * Drugs associated with fatty liver (i.e. amiodarone, methotrexate, systemic glucocorticoids, tamoxifen, anabolic steroids, valproic acid) for more than 4 weeks prior to baseline or during study * Recent, current, or planned upcoming pregnancy or current perimenopausal status * Renal impairment (glomerular filtration rate \<45 ml/min/1.73m or potassium levels \> 5.0 mmol/L) * Androgen receptor antagonist use (i.e. spironolactone or flutamide) for more than 3 months within one year prior to baseline

Treatments Being Tested

DRUG

Bicalutamide 50 mg

Bicalutamide capsules will be prepared from U.S. Pharmacopeia grade powder at a dose of 50 mg

DRUG

Placebo

Matching placebo capsules of the same color, mass, and appearance to the bicalutamide capsules will be filled using microcrystalline cellulose powder.

Locations (1)

University of California San Francisco

San Francisco, California, United States