Insulin Resistance and Androgen Deprivation Therapy

Phase 2

Withdrawn

• Conditions: Prostate Cancer; Insulin Resistance
• Interventions: Drug: placebo tablet; Drug: Pioglitazone 30 mg

• Registration Number: NCT04995978
• Lead Sponsor: St. Louis University

Brief Summary

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.

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 Timeline

• Study First Submitted: 2021-08-02
• Study First Submitted QC: 2021-08-02
• Study First Posted: 2021-08-09
• Study Start: 2021-12-01
• Primary Completion: 2023-01-18
• Study Completion: 2023-01-18
• Status Verified: 2023-06
• Last Update Submitted: 2023-06-21
• Last Update Posted: 2023-06-23

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: Male
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
placebo	placebo tablet	-
Pioglitazone	Pioglitazone 30 mg	-

Primary Outcome Measures

Name	Time	Method
insulin sensitivity	6 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Saint Louis Univeristy; 🇺🇸 Saint Louis, Missouri, United States