Bicalutamide for NAFLD and PCOS

Overseen By Elle K Oberweis-Manion

Age: 18 - 65

Sex: Female

Trial Phase: Phase 1

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 This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 6 months

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests bicalutamide, a medication that blocks certain hormones, to determine its effectiveness for liver issues in women with both PCOS and fatty liver disease. Researchers aim to discover if blocking these hormones can prevent liver damage. Participants will take either bicalutamide or a placebo daily for six months. Suitable candidates have PCOS with liver problem signs and have not recently undergone weight loss surgery or been pregnant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

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.

Is there any evidence suggesting that Bicalutamide is likely to be safe for humans?

Research shows that bicalutamide is usually well-tolerated in studies for other conditions. It is often used to treat prostate cancer in men, and its safety is well-documented in that group. Common side effects in these studies included hot flashes, breast tenderness, and fatigue. More serious side effects occurred less frequently.

As a Phase 1 trial, this treatment is in the early stages of testing for this specific use, so researchers are closely monitoring safety. This phase primarily ensures the treatment's safety for participants. While bicalutamide has been used for other conditions, its effects in women with nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) are still under investigation. Researchers will closely monitor participants' health to identify any side effects specific to this new use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Bicalutamide is unique because it offers a novel approach to treating NAFLD and PCOS by targeting androgen receptors, unlike current options that typically focus on lifestyle changes, insulin sensitizers, or anti-inflammatory drugs. This mechanism of action is particularly promising for conditions like PCOS, where androgen excess is a key factor. Researchers are excited because bicalutamide's targeted approach could potentially provide more effective symptom management and improve liver and hormonal health in ways existing treatments do not.

What evidence suggests that Bicalutamide might be an effective treatment for NASH in women with PCOS?

Research shows that bicalutamide, initially used for prostate cancer, might also help treat conditions like nonalcoholic steatohepatitis (NASH) and polycystic ovary syndrome (PCOS). In earlier studies, bicalutamide showed promise in reducing liver inflammation and scarring linked to NASH. This trial will evaluate bicalutamide's potential benefits for these conditions. Participants will receive either bicalutamide or a placebo. The medication blocks certain hormones, which may help manage hormone imbalances contributing to these conditions. Early results suggest that targeting these hormones might improve liver health and lower risk factors related to PCOS and nonalcoholic fatty liver disease (NAFLD). However, more research is needed to confirm its effectiveness for these specific conditions. ^{1 2 4 6 7}

Who Is on the Research Team?

Monika Sarkar

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Bicalutamide

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.

How Is the Trial Designed?

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 European Union, United States, Japan, Canada for the following indications:

Approved in European Union as Casodex for:

• Metastatic prostate cancer
• Locally advanced prostate cancer

Approved in United States as Casodex for:

• Metastatic prostate cancer

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+

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

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

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 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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05979389

Bicalutamide Therapy in Young Women With NAFLD and ... Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is projected to be the leading cause of cirrhosis in the United States ...

2. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05979389

Bicalutamide Therapy in Young Women With NAFLD and PCOS ... Nonalcoholic Fatty Liver Disease (NAFLD) and Polycystic Ovary Syndrome (PCOS) ... Non-alcoholic Fatty Liver Disease, bicalutamide, Bicalutamide ...

3. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/453318

Bicalutamide Therapy in Young Women With NAFLD and ... Bicalutamide Therapy in Young Women With NAFLD and PCOS ... Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and scarring is projected to be ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12440274/

Baicalin mitigates polycystic ovary syndrome-associated non ... Key words: polycystic ovary syndrome, non-alcoholic fatty liver disease ... Despite advances in understanding PCOS-associated NAFLD, effective treatment ...

5. allclinicaltrials.com allclinicaltrials.com/study/NCT05979389

Bicalutamide Therapy in Young Women With NAFLD and PCOS Nonalcoholic steatohepatitis (NASH), or fat-related liver inflammation and ... Bicalutamide with NAFLDBicalutamide Therapy in Young Women With NAFLD and PCOS.

6. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK459251/

Polycystic Ovarian Syndrome - StatPearls - NCBI Bookshelf Women with PCOS have 3 times the increased risk of MASLD, formerly known as nonalcoholic fatty liver disease (NAFLD); MASLD has been associated ...

7. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT05647356

NCT05647356 | The RolE oF Androgen Excess in MUscle ... Women with PCOS are at increased risk of metabolic complications such as diabetes, non-alcoholic fatty liver disease, high blood pressure and heart disease.