Clincosm LogoSign in Get a demo

Bicalutamide Therapy in Young Women With NAFLD and PCOS

Sponsor
University of California, San Francisco (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05979389
Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
50
Enrollment
1
Location
2
Arms
60
Anticipated Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bicalutamide 50 mg
  • Drug: Placebo
 Phase 1

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 Design

Study Type:
Interventional
Anticipated Enrollment :
50 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
The following treatment regimens will be used: Experimental treatment - bicalutamide, 50 mg once daily Placebo or Comparator - one capsule, once dailyThe following treatment regimens will be used:Experimental treatment - bicalutamide, 50 mg once daily Placebo or Comparator - one capsule, once daily
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Due to the objectives of the study, the identity of test and control treatments will not be known to investigators, research staff, or patients. The following study procedures will be in place to ensure double-blind administration of study treatments Access to the randomization code will be strictly controlled. A color and size-matched placebo capsule that looks identical to the bicalutamide capsule will be used. Packaging and labeling of test and control treatments will be identical to maintain the blind. The study blind will be broken on completion of the clinical study, after all study endpoints have been ascertained by blinded study coordinators and after the study database has been locked. During the study, the blind may be broken only in emergencies when knowledge of the patient's treatment group is necessary for further patient management. The University of California San Francisco investigational pharmacy would then be notified and responsible for unblinding.
Primary Purpose:
Other
Official Title:
Pilot Trial of Bicalutamide Versus Placebo in Reproductive-Aged Women With Nonalcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovary Syndrome (PCOS)
Anticipated Study Start Date :
Aug 1, 2023
Anticipated Primary Completion Date :
Aug 1, 2028
Anticipated Study Completion Date :
Aug 1, 2028

Arms and Interventions

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.

    Outcome Measures

    Primary Outcome Measures

    1. Change in liver stiffness on Magnetic Resonance Elastography (MRE) [Baseline and 6 months]

      The investigators will assess for change in the MRE quantified liver stiffness in kilopascals (kPA)

    Secondary Outcome Measures

    1. Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF) [Baseline and 6 months]

      The investigators will assess for percent change in fat fraction by MRI-PDFF

    2. Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI) [Baseline and 6 months]

      The investigators will assess for percent change in VAT as quantified by MRI

    3. Change HOMA-IR (Homeostatic model assessment (HOMA) for insulin resistance (IR)) [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

    4. Change in the NAFLD Activity Score (NAS) on a scale from 0 (low activity) to 8 (high activity) [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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 40 Years
    Sexes Eligible for Study:
    Female
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of California San Francisco San Francisco California United States 94143

    Sponsors and Collaborators

    • University of California, San Francisco
    • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    University of California, San Francisco
    ClinicalTrials.gov Identifier:
    NCT05979389
    Other Study ID Numbers:
    • 23-39274
    • 1R01DK134633-01A1
    First Posted:
    Aug 7, 2023
    Last Update Posted:
    Aug 8, 2023
    Last Verified:
    Aug 1, 2023
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    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
    Additional relevant MeSH terms:
    Non-alcoholic Fatty Liver Disease
    Bicalutamide

    Study Results

    No Results Posted as of Aug 8, 2023