Insulin Resistance and Androgen Deprivation Therapy

Insulin Resistance in Men With Prostate Cancer on Androgen Deprivation Therapy

Prostate cancer is the most common malignancy amongst men in United States. Androgen deprivation therapy (ADT) with long acting gonadotropin releasing hormone agonists is routinely used as adjuvant therapy in intermediate and high risk localized or locally advanced prostate cancer. Since ADT induces insulin resistance and diabetes, it is important that cellular and molecular effects of ADT are investigated to define precisely the mechanisms involved in the pathogenesis of insulin resistance. Pioglitazone, a known insulin sensitizer, may provide amelioration of insulin resistance in these patients.

Study Overview

• Status: Withdrawn
• Conditions: Insulin Resistance; Prostate Cancer
• Intervention / Treatment: Drug: Pioglitazone 30 mg; Drug: placebo tablet

Detailed Description

Investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled trial in 44 men with nonmetastatic prostate cancer who are receiving ADT with long acting GnRH agonist (study group). Study subjects will undergo insulin clamp, subcutaneous fat biopsy, muscle biopsy, have a blood sample taken and fibroscan performed prior to randomization of study drug. They will then be randomized to 30 mg pioglitazone or placebo tablet daily for 6 months. Blood samples will be drawn 2 and 4 months following the initiation of the study drug. The final study visit will be at 6 months. Subjects will undergo clamp, fat biopsy, muscle biopsy, blood sampling, fibroscan and will be discharged from the study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • Saint Louis Univeristy

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Prostate cancer, non-metastatic
• Have been on ADT with long acting GnRH agonist continuously for last 3 months, AND planning to continue ADT for at least 6 months

Exclusion Criteria:

• Used pioglitazone in last 6 months
• Heart Failure NYHA Class 3 or 4
• Known to have osteoporosis at this time.
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo tablet; Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.
Experimental: Pioglitazone	Drug: Pioglitazone 30 mg; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
insulin sensitivity	The primary endpoint of the study is to detect a difference in insulin sensitivity as measured by whole body glucose uptake during clamps after treatment with pioglitazone as compared to placebo.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin signaling (Insulin receptor substrate expression in fat tissue)	A secondary endpoint for the study will be comparison of the relative change from baseline in insulin signaling after pioglitazone or placebo.	6 months

Collaborators and Investigators

• Sponsor: St. Louis University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Actual): January 18, 2023
• Study Completion (Actual): January 18, 2023

Study Registration Dates

• First Submitted: August 2, 2021
• First Submitted That Met QC Criteria: August 2, 2021
• First Posted (Actual): August 9, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Genital Neoplasms, Male; Prostatic Diseases; Hyperinsulinism; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Prostatic Neoplasms; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Pioglitazone
• Other Study ID Numbers: 31991

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes