Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer

This is a double-blind, randomized, placebo-controlled trial of daily oral genistein in 24
men initiating Androgen Deprivation Therapy (ADT) for prostate cancer (PCa). Genistein is a
natural supplement that comes from soy. The purpose of this study is to see if genistein has
any effect on preventing or reducing heart disease and diabetes risk in men receiving ADT for
PCa. A combination of nutritional measures, blood markers and imaging tools will assess body
composition, lipid levels and insulin resistance. Information from this study will increase
understanding of interventions which may prevent or reduce health risks during prostate
cancer treatment.

All participants will receive standard counseling for diet and exercise by their oncology
care team. Participants will be asked to withhold from any additional dietary supplements
(with the exception of 1 standard daily multivitamin) during the study period. Participants
will also be asked to complete a food diary for three days (on two weekdays and 1 weekend
day).

Subjects will be randomized and stratified by diabetes status to either 60 mg/day oral
genistein (30 mg taken twice daily), or matching placebo. The goal for randomizing based on
diabetes status is to ensure approximately the same number of subjects who have diabetes and
do not have diabetes receive genistein and placebo.

During follow-up, subjects will receive weekly reminders via phone call, text, or email to
enhance compliance and monitor for potential adverse events. The 3-month study visit will be
scheduled to coincide with the subject's standard of care follow-up visit. Three-month
assessments will be the same as baseline assessments.

Investigators seek to assess indexes of insulin dynamics (insulin sensitivity and secretion)
determined from an oral glucose tolerance test before and 12 weeks after a daily genistein or
placebo supplement. Measures of vascular function before and 12 weeks after a daily genistein
or placebo supplement will also be assessed via ultrasound along with other metabolic
measures via blood draw.

Inclusion Criteria:

- Medical indication for androgen deprivation therapy (ADT) via luteinizing
hormone-releasing hormone (LHRH) analog ± oral anti-androgen

- Diagnosis of prostate cancer

- ECOG performance status ≤ 2

- Life expectancy > 6 months

- Ability to provide informed consent

Exclusion Criteria:

- Transmural myocardial infarction, unstable angina, or congestive heart failure
requiring hospitalization within the last 6 months

- Acute coronary event within the past month

- Use of intravenous antibiotics within the last 6 months

- Chronic liver disease

- Current use of cytotoxic or immunosuppressive drugs

- Chronic glucocorticoid or acute glucocorticoid or other synthetic steroid intake
within the last month

- Chronic diarrhea or malabsorptive diseases (e.g., Crohn's disease)

- Stage 5 chronic kidney disease or need for hemodialysis

- Supplemental oxygen dependency

- Brain metastasis

- Severe cognitive dysfunction impairing ability to provide informed consent or consume
study drug

- Dysphagia or requirement for artificial feeding

- Surgery or hospitalization within the last month

- Chemotherapy or radiation therapy within the last 60 days

- Insulin dependent diabetes

- HIV/AIDS

- History of organ transplant

- ECOG performance status > 2