Insulin Resistance Following ADT for Prostate CA

NCT04658849 | Withdrawn Early Phase 1 FDA Drug

• 1 other identifier: 30509
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Prostate cancer is the most common cancer in men in the United States. Suppression of male hormone levels by using GnRH agonist ("hormone blocking therapy") for a few years is routinely used to treat prostate cancer. While the treatment is very effective, it decreases muscle mass and increases fat mass. This results in a decrease in insulin action (also called insulin resistance) and increases the likelihood of diabetes. It may also contribute to risk of developing heart disease. The investigators propose to conduct a trial that will:-

1. 1.study the mechanisms through which GnRH agonists cause insulin resistance.
2. 2.Evaluate a treatment that can decrease insulin resistance. This is a randomized, placebo controlled, double-blind trial. Forty-four men with prostate cancer will be recruited in the trial before starting GnRH agonist therapy. Participants will undergo metabolic studies to evaluate insulin action (called insulin clamp), abdominal fat tissue biopsy to study insulin action at the cellular level and blood draws. The study volunteers will then be given either a placebo tablet or pioglitazone tablet to take once a day for the next six months. The metabolic tests, blood test and fat tissue biopsy will be obtained again at the end of the study.

Conditions

Insulin Resistance; Prostate Cancer

Keywords

Androgen Deprivation Therapy

Outcome Measures

Primary Outcomes (1)

• Insulin Sensitivity

  The primary endpoint of the study is to detect a difference in insulin sensitivity as measured by whole body glucose uptake during EHC after treatment with pioglitazone as compared to placebo.

  6 months

Secondary Outcomes (3)

• HOMA-IR

  6 months

• Insulin signaling

  6 months

• C Reactive Protein

  6 months

Study Arms (2)

Pioglitazone Arm

EXPERIMENTAL

Subjects will self-administer a 30 mg pioglitazone oral tablet daily for 6 months. For patient taking a diabetic regimen of gemfibrozil, the dose will be 15 mg daily.

Drug: Pioglitazone 30 Mg Oral Tablet

Placebo Arm

PLACEBO COMPARATOR

Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.

Drug: Pioglitazone placebo tablet

Interventions

Pioglitazone 30 Mg Oral Tablet DRUG

Subjects will self-administer a 30 mg pioglitazone oral tablet daily for 6 months. For patient taking a diabetic regimen of gemfibrozil, the dose will be 15 mg daily.

Also known as: Actos

Pioglitazone Arm

Pioglitazone placebo tablet DRUG

Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.

Also known as: Placebo

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men between the ages of 18-85 years
• Prostate cancer, non-metastatic
• Planning to initiate ADT with long acting GnRH agonist

You may not qualify if:

• Prior history of ADT use
• Used pioglitazone in last 6 months
• Congestive Heart Failure Class 3 or 4
• Osteoporosis, including history of fragility fracture
• history of bladder cancer
• Hemoglobin \<8 g/dl
• eGFR \<15 ml/min/1.73m2
• liver enzymes (ALT or AST) \>3 times the upper limit of normal

Sponsors & Collaborators

• St. Louis University: lead

Study Sites (1)

Saint Louis University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Insulin Resistance; Prostatic Neoplasms

Interventions

Pioglitazone; Tablets

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Sameer Siddiqui, MD

  St. Louis University

  PRINCIPAL INVESTIGATOR

• Sandeep Dhindsa, MD

  St. Louis University

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: C. Rollins Hanlon Endowed Chair of Surgery

Model Details: We plan to conduct a prospective, randomized, double-blind, placebo-controlled trial in 44 men with nonmetastatic prostate cancer who will receive ADT with long acting GnRH agonist.

Study Record Dates

• First Submitted: October 27, 2020
• First Posted: December 9, 2020
• Study Start: December 2, 2020
• Primary Completion: March 29, 2023
• Study Completion: March 29, 2023
• Last Updated: May 15, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)