Bicalutamide Therapy in Young Women With NAFLD and PCOS

NCT05979389 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 23-39274R01DK134633-01A1
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

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.

Conditions

NAFLD; PCOS

Outcome Measures

Primary Outcomes (1)

• Change in liver stiffness on Magnetic Resonance Elastography (MRE)

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

  Baseline and 6 months

Secondary Outcomes (4)

• Change in hepatic steatosis by Magnetic Resonance Proton Density Fat Fraction (PDFF)

  Baseline and 6 months

• Change in visceral adipose tissue (VAT) volume by Magnetic Resonance Imaging (MRI)

  Baseline and 6 months

• Change HOMA-IR (Homeostatic model assessment (HOMA) for insulin resistance (IR))

  Baseline and 6 months

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

  Baseline and 6 months

Study Arms (2)

Bicalutamide

EXPERIMENTAL

50 mg capsule administered orally once daily for 6 months

Drug: Bicalutamide 50 mg

Placebo

PLACEBO COMPARATOR

Matching placebo capsule administered orally once daily for 6 months

Drug: Placebo

Interventions

Bicalutamide 50 mg DRUG

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

Also known as: Casodex

Bicalutamide

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

University of California San Francisco

San Francisco, California, 94143, United States

RECRUITING

Related Publications (11)

• Maldonado SS, Grab J, Wang CW, Huddleston H, Cedars M, Sarkar M. Polycystic ovary syndrome is associated with nonalcoholic steatohepatitis in women of reproductive age. Hepatol Commun. 2022 Oct;6(10):2634-2639. doi: 10.1002/hep4.2039. Epub 2022 Jul 21.

  PMID: 35861548 BACKGROUND

• Sarkar MA, Suzuki A, Abdelmalek MF, Yates KP, Wilson LA, Bass NM, Gill R, Cedars M, Terrault N; NASH Clinical Research Network. Testosterone is Associated With Nonalcoholic Steatohepatitis and Fibrosis in Premenopausal Women With NAFLD. Clin Gastroenterol Hepatol. 2021 Jun;19(6):1267-1274.e1. doi: 10.1016/j.cgh.2020.09.045. Epub 2020 Oct 1.

  PMID: 33010412 BACKGROUND

• Sanchez-Garrido MA, Tena-Sempere M. Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies. Mol Metab. 2020 May;35:100937. doi: 10.1016/j.molmet.2020.01.001. Epub 2020 Feb 5.

  PMID: 32244180 BACKGROUND

• O'Reilly MW, Kempegowda P, Walsh M, Taylor AE, Manolopoulos KN, Allwood JW, Semple RK, Hebenstreit D, Dunn WB, Tomlinson JW, Arlt W. AKR1C3-Mediated Adipose Androgen Generation Drives Lipotoxicity in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017 Sep 1;102(9):3327-3339. doi: 10.1210/jc.2017-00947.

  PMID: 28645211 BACKGROUND

• Dieudonne MN, Pecquery R, Boumediene A, Leneveu MC, Giudicelli Y. Androgen receptors in human preadipocytes and adipocytes: regional specificities and regulation by sex steroids. Am J Physiol. 1998 Jun;274(6):C1645-52. doi: 10.1152/ajpcell.1998.274.6.C1645.

  PMID: 9611130 BACKGROUND

• Gambineri A, Patton L, Vaccina A, Cacciari M, Morselli-Labate AM, Cavazza C, Pagotto U, Pasquali R. Treatment with flutamide, metformin, and their combination added to a hypocaloric diet in overweight-obese women with polycystic ovary syndrome: a randomized, 12-month, placebo-controlled study. J Clin Endocrinol Metab. 2006 Oct;91(10):3970-80. doi: 10.1210/jc.2005-2250. Epub 2006 Jul 25.

  PMID: 16868063 BACKGROUND

• Cusi K. Role of obesity and lipotoxicity in the development of nonalcoholic steatohepatitis: pathophysiology and clinical implications. Gastroenterology. 2012 Apr;142(4):711-725.e6. doi: 10.1053/j.gastro.2012.02.003. Epub 2012 Feb 8.

  PMID: 22326434 BACKGROUND

• Macut D, Tziomalos K, Bozic-Antic I, Bjekic-Macut J, Katsikis I, Papadakis E, Andric Z, Panidis D. Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Hum Reprod. 2016 Jun;31(6):1347-53. doi: 10.1093/humrep/dew076. Epub 2016 Apr 12.

  PMID: 27076501 BACKGROUND

• Kumarendran B, O'Reilly MW, Manolopoulos KN, Toulis KA, Gokhale KM, Sitch AJ, Wijeyaratne CN, Coomarasamy A, Arlt W, Nirantharakumar K. Polycystic ovary syndrome, androgen excess, and the risk of nonalcoholic fatty liver disease in women: A longitudinal study based on a United Kingdom primary care database. PLoS Med. 2018 Mar 28;15(3):e1002542. doi: 10.1371/journal.pmed.1002542. eCollection 2018 Mar.

  PMID: 29590099 BACKGROUND

• Ismail FF, Meah N, Trindade de Carvalho L, Bhoyrul B, Wall D, Sinclair R. Safety of oral bicalutamide in female pattern hair loss: A retrospective review of 316 patients. J Am Acad Dermatol. 2020 Nov;83(5):1478-1479. doi: 10.1016/j.jaad.2020.03.034. Epub 2020 Mar 22. No abstract available.

  PMID: 32213304 BACKGROUND

• Fernandez-Nieto D, Saceda-Corralo D, Rodrigues-Barata R, Hermosa-Gelbard A, Moreno-Arrones O, Jimenez-Cauhe J, Ortega-Quijano D, Vano-Galvan S. Oral bicalutamide for female pattern hair loss: A pilot study. Dermatol Ther. 2019 Nov;32(6):e13096. doi: 10.1111/dth.13096. Epub 2019 Oct 10. No abstract available.

  PMID: 31579984 BACKGROUND

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

bicalutamide

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Monika A Sarkar, MD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lily Carbullido

CONTACT

(415)-502-3725; MyLiverHealth@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The following treatment regimens will be used: * Experimental treatment - bicalutamide, 50 mg once daily * Placebo or Comparator - one capsule, once daily

Study Record Dates

• First Submitted: July 28, 2023
• First Posted: August 7, 2023
• Study Start: February 14, 2024
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)