Bicalutamide for NAFLD and PCOS

Overseen by Monika Sarkar

Age: 18 - 65

Sex: Female

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of California, San Francisco

Must not be taking: Steroids, Valproic acid, others

Disqualifiers: Diabetes, Alcohol use, Liver disease, others

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests bicalutamide, a medication that blocks certain hormones, in women with NAFLD and PCOS. The goal is to see if it can reduce liver damage by stopping harmful hormone effects.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications associated with fatty liver, such as amiodarone, methotrexate, and others, for more than 4 weeks before starting the study. Additionally, you cannot have used androgen receptor antagonists like spironolactone or flutamide for more than 3 months within the past year.

How is the drug Bicalutamide unique for treating NAFLD and PCOS?

Bicalutamide is unique because it is primarily used as an anti-androgen (a substance that blocks male hormones) in prostate cancer treatment, and its use for NAFLD and PCOS is novel, as these conditions are not typically treated with anti-androgens. This approach may offer a new way to address the hormonal imbalances associated with PCOS and its link to NAFLD. ^{1 2 3 4 5}

Research Team

Monika Sarkar

Principal Investigator

University of California, San Francisco

Eligibility Criteria

This trial is for young women aged 18-40 with PCOS and NAFLD, diagnosed through liver biopsy or specific tests. Participants should not have used certain drugs that affect the liver, have uncontrolled diabetes, severe kidney issues, a history of excessive alcohol use, other chronic liver diseases or be pregnant.

Inclusion Criteria

I am a woman aged 18-40 with PCOS and high male hormone levels.

I have been diagnosed with NASH through a liver biopsy or specific liver tests.

Exclusion Criteria

I am HIV positive.

My kidney function is impaired or my potassium levels are high.

I have a chronic liver condition or cirrhosis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of bicalutamide or placebo once daily for 6 months

6 months

6 visits (in-person) at Month 1, 2, 3, 4, 5, and 6

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month

1 visit (telephone)

Treatment Details

Interventions

• Bicalutamide (Hormone Therapy)

Trial Overview The study is testing Bicalutamide's effectiveness in treating fat-related liver inflammation in women with PCOS. It compares Bicalutamide (50 mg) against a placebo to see if it can improve NASH by targeting androgen receptors.

Participant Groups

Group I: Bicalutamide Experimental Treatment 1 Intervention

50 mg capsule administered orally once daily for 6 months

Group II: Placebo Placebo Group 1 Intervention

Matching placebo capsule administered orally once daily for 6 months

Bicalutamide is already approved in Japan, Canada for the following indications:

Approved in Japan as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in Canada as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Suresh Gunasekaran

University of California, San Francisco

Chief Executive Officer since 2022

MBA from Southern Methodist University

Dr. Lukejohn Day

University of California, San Francisco

Chief Medical Officer

MD from Stanford University School of Medicine

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Dr. Griffin P. Rodgers

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

Chief Executive Officer since 2007

MD, M.A.C.P.

Dr. Griffin P. Rodgers

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

Chief Medical Officer since 2007

MD, M.A.C.P.

Findings from Research

In a study of 120 nonpregnant patients (60 with PCOS and 60 without), those with polycystic ovary syndrome (PCOS) showed a significantly higher prevalence of nonalcoholic fatty liver disease (NAFLD) at 42%, compared to 20% in the control group.

The PCOS group also exhibited higher levels of liver enzymes (ALT), insulin resistance, and body mass index, indicating a strong association between PCOS and NAFLD, highlighting the need for liver health screening in PCOS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevalence of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome: a case-control study]. Zheng, RH., Ding, CF.[2014]

In a study of 600 Caucasian women with polycystic ovary syndrome (PCOS), insulin resistance (IR) and lipid accumulation product (LAP) were found to be independently associated with a higher prevalence of non-alcoholic fatty liver disease (NAFLD), which was present in 50.6% of the PCOS group compared to 34.0% in controls.

The study highlighted that women with PCOS exhibited significantly higher levels of waist circumference, LAP, insulin, and triglycerides, indicating that these factors may contribute to the increased risk of NAFLD and related conditions like type 2 diabetes and cardiovascular disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. Macut, D., Tziomalos, K., Božić-Antić, I., et al.[2022]

Women with polycystic ovary syndrome (PCOS) have a significantly higher prevalence of nonalcoholic fatty liver disease (NAFLD) compared to controls (30.7% vs 17.5%), with severity increasing alongside body mass index (BMI) and other metabolic factors.

The study highlights that abdominal obesity in PCOS patients is linked to a greater prevalence of NAFLD, suggesting that insulin resistance and metabolic syndrome are critical factors in the development of liver disease in these women, emphasizing the need for targeted screening and treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effect of obesity on nonalcoholic fatty liver disease in Chinese women with polycystic ovary syndrome]. Qu, ZY., Shi, YH., Zhao, DN., et al.[2014]

In a study of 25 women with polycystic ovary syndrome (PCOS), supplementation with 4g/day of omega-3 fatty acids significantly reduced liver fat content compared to placebo, indicating a potential therapeutic benefit for managing nonalcoholic fatty liver disease (NAFLD).

Omega-3 fatty acids also improved cardiovascular risk factors, leading to reductions in triglycerides and both systolic and diastolic blood pressure, suggesting that they may have broader health benefits for women with PCOS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. Cussons, AJ., Watts, GF., Mori, TA., et al.[2015]

In a study of 140 women with polycystic ovarian syndrome (PCOS), 83.6% were found to have non-alcoholic fatty liver disease (NAFLD), significantly higher than the 45.7% prevalence in matched controls, indicating a strong association between PCOS and NAFLD.

The study highlights the importance of screening for NAFLD in women with PCOS, especially those seeking infertility treatment, as early detection can help prevent serious liver complications like cirrhosis. Non-invasive methods like Fibroscan are effective for assessing liver fibrosis in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women. Siwatch, S., Singh, V., Dhaliwal, LK., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Prevalence of nonalcoholic fatty liver disease in patients with polycystic ovary syndrome: a case-control study]. [2014]

2. England pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease is associated with insulin resistance and lipid accumulation product in women with polycystic ovary syndrome. [2022]

3. China pubmed.ncbi.nlm.nih.gov

[Effect of obesity on nonalcoholic fatty liver disease in Chinese women with polycystic ovary syndrome]. [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Omega-3 fatty acid supplementation decreases liver fat content in polycystic ovary syndrome: a randomized controlled trial employing proton magnetic resonance spectroscopy. [2015]

5. England pubmed.ncbi.nlm.nih.gov

Non-alcoholic fatty liver disease in polycystic ovarian syndrome in Indian women. [2022]