Insulin Resistance and Androgen Deprivation Therapy
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 2 |
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 Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: Pioglitazone
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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.
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Placebo Comparator: placebo
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Drug: placebo tablet
Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.
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Outcome Measures
Primary Outcome Measures
- 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
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Prostate cancer, non-metastatic
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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:
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Used pioglitazone in last 6 months
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Heart Failure NYHA Class 3 or 4
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Known to have osteoporosis at this time.
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history of bladder cancer
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Hemoglobin <8 g/dl
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eGFR <15 ml/min/1.73m2
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liver enzymes (ALT or AST) >3 times the upper limit of normal
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Saint Louis Univeristy | Saint Louis | Missouri | United States | 63104 |
Sponsors and Collaborators
- St. Louis University
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 31991