Insulin Resistance and Androgen Deprivation Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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Insulin Resistance in Men With Prostate Cancer on Androgen Deprivation Therapy

Conditions
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Prostate Cancer, Insulin Resistance

Intervention / Treatment
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* Drug: Pioglitazone 30 mg
* Drug: placebo tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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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 |