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

• ClinicalTrials.gov Identifier: NCT02766478
• Recruitment Status: Suspended
• First Posted: May 9, 2016
• Last Update Posted: May 29, 2020
• Sponsor: Emory University
• Information provided by (Responsible Party): Jessica Alvarez, Emory University

Study Description

Brief Summary:

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 Androgen Deprivation Therapy for prostate cancer. A combination of nutritional measures, blood markers and imaging tools will assess body composition, lipid levels and insulin resistance. Information from this pilot study will increase understanding of interventions which may prevent or reduce health risks during prostate cancer treatment. This project involves 24 men who will receive androgen deprivation therapy for prostate cancer.

Condition or disease	Intervention/treatment	Phase
Prostate Cancer	Drug: Genistein; Drug: Placebo	Phase 2

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer
• Actual Study Start Date: October 16, 2017
• Estimated Primary Completion Date: October 2020
• Estimated Study Completion Date: October 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Genistein; Participants with and without diabetes will receive 60 mg/day oral genistein (30 mg taken twice daily) for 12 weeks.	Drug: Genistein; Genistein is a natural supplement that comes from soy. Genistein will be taken orally (30 mg twice daily) for 12 weeks.
Placebo Comparator: Placebo; Participants with and without diabetes will receive placebo taken twice daily for 12 weeks.	Drug: Placebo; A placebo pill will be taken orally for 12 weeks.

Outcome Measures

Primary Outcome Measures :

1. Change in Matsuda Index of Whole-Body Insulin Sensitivity [ Time Frame: Baseline, Week 12 ]
   The Matsuda index is a measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT).
2. Change in β-cell Insulin Secretion Capacity assessed by the Insulinogenic Index [ Time Frame: Baseline, Week 12 ]
   β-cell insulin secretion will be assessed by the insulinogenic index by measuring the ratio of insulin to glucose.

Secondary Outcome Measures :

1. Change in Arterial Stiffness [ Time Frame: Baseline, Week 12 ]
   Arterial stiffness will be assessed by applanation tonometry.
2. Change in Vascular Endothelial Function [ Time Frame: Baseline, Week 12 ]
   Vascular endothelial function will be measured with flow-mediated dilation (FMD) via ultrasound.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Georgia

Emory University

Atlanta, Georgia, United States, 30322

Sponsors and Collaborators

Emory University

Investigators

• Principal Investigator: Jessica Alvarez, PhD; Emory University

More Information

• Responsible Party: Jessica Alvarez, Assistant Professor, Emory University
• ClinicalTrials.gov Identifier: NCT02766478
• Other Study ID Numbers: IRB00086186
• First Posted: May 9, 2016
• Last Update Posted: May 29, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Prostatic Neoplasms; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Genistein; Anticarcinogenic Agents; Protective Agents; Physiological Effects of Drugs; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Phytoestrogens; Estrogens, Non-Steroidal; Estrogens; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists