Bicalutamide Therapy in Young Women With NAFLD and PCOS

February 15, 2024 updated by: University of California, San Francisco

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a single center, double-blind, placebo-controlled, randomized, (1:1) parallel group pilot clinical trial of bicalutamide in women with either biopsy-proven or believed NAFLD receiving 6 months of bicalutamide or placebo. 50 women are targeted for enrollment. Each participant will be administered a single dose of bicalutamide or placebo once daily for a total of 6 months. In person evaluations will take place at Month 1, 2, 3, 4, 5, and 6. There will be a telephone follow up visit within 1 month of end of treatment. 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. 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)

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California San Francisco
        • Contact:
        • Principal Investigator:
          • Monika Sarkar, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Women aged 18-40 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Bicalutamide
50 mg capsule administered orally once daily for 6 months
Drug: Bicalutamide 50 mg
Bicalutamide capsules will be prepared from U.S. Pharmacopeia grade powder at a dose of 50 mg
Other Names:
  • Casodex
Placebo Comparator: Placebo
Matching placebo capsule administered orally once daily for 6 months
Drug: Placebo
Matching placebo capsules of the same color, mass, and appearance to the bicalutamide capsules will be filled using microcrystalline cellulose powder.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in liver stiffness on Magnetic Resonance Elastography (MRE)
Time Frame: Baseline and 6 months
The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)
Baseline and 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change HOMA-IR (Homeostatic model assessment (HOMA) for insulin resistance (IR))
Time Frame: Baseline and 6 months
The investigators will assess change in continuous measures of HOMA-IR as insulin resistance is known to contribute to NASH progression
Baseline and 6 months
Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF)
Time Frame: Baseline and 6 months
The investigators will assess for percent change in fat fraction by MRI-PDFF
Baseline and 6 months
Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI)
Time Frame: Baseline and 6 months
The investigators will assess for percent change in VAT as quantified by MRI
Baseline and 6 months
Change in the NAFLD Activity Score (NAS) on a scale from 0 (low activity) to 8 (high activity)
Time Frame: Baseline and 6 months
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).
Baseline and 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

  • Principal Investigator: Monika A Sarkar, MD, MAS, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2024

Primary Completion (Estimated)

August 1, 2028

Study Completion (Estimated)

August 1, 2028

Study Registration Dates

First Submitted

July 28, 2023

First Submitted That Met QC Criteria

July 28, 2023

First Posted (Actual)

August 7, 2023

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 23-39274
  • R01DK134633-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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