Prostate Cancer, Insulin Resistance
Conditions
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.
Interventions
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.
DRUGplacebo tablet
Subjects will self-administer an oral placebo tablet containing cellulose daily for 6 months.
Sponsors
St. Louis University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 85 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Outcome results
None listed