Androgen Deprivation Therapy Study

Study Overview
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Brief Summary
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The purpose of this study is to examine the link between low testosterone and insulin resistance/diabetes in men undergoing androgen deprivation therapy for prostate cancer. The study will also evaluate other cardiovascular risk factors in these men.

Detailed Description
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Lowering of testosterone levels, by medications or surgery (Androgen Deprivation Therapy or ADT), is commonly used in the treatment of prostate cancer. The adverse effects of low testosterone include decreased sex drive, impotence, decreased lean body mass and muscle strength, increased fat mass, decreased quality of life and osteoporosis. An increase in body fat and decrease in lean body mass may contribute to a decrease in the body's ability to use insulin effectively, leading to insulin resistance and diabetes. Low testosterone levels are also associated with elevated total cholesterol, LDL-cholesterol and triglycerides. Two groups of non-diabetic men will be studied: Men with known history of prostate cancer who were treated with surgery and/or radiation therapy and are now in remission and not receiving androgen deprivation therapy (non-ADT group). Men with newly diagnosed or known history of prostate cancer who are being advised by their physicians to begin androgen deprivation therapy (ADT group). The non-ADT group and half of the ADT group will be observed for the development of insulin resistance/diabetes. The other half of the ADT group will receive a diabetes medication called Pioglitazone (Actos) to evaluate any beneficial effects of this medication in the prevention of metabolic dysfunction. The study will consist of a screening visit and 6 additional study visits throughout one year. Procedures during this study include blood draws, MRI, CT, DEXA scan, insulin clamp procedures, oral glucose tolerance tests, carotid IMT, pulse wave velocity, neuropsychological testing, physical exams and an optional muscle biopsy.

Official Title
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Metabolic and Cardiovascular Complications in Men With Prostate Cancer Undergoing Long-term Androgen Deprivation Therapy

Conditions
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Hypogonadism, Metabolic Syndrome, Diabetes, Inflammation

Intervention / Treatment
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* Drug: Pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men 18 years of age or older with prostate cancer Planning to undergo long-term (at least 12 months) ADT No known history of diabetes No history of ADT Exclusion Criteria: History of ADT or any prior diagnosis of hypogonadism Fasting glucose or oral glucose tolerance test results in the diabetic range Heart failure (NY classification III or IV) Testosterone level less than 250 ng/dl on screening History of heart attack or open-heart surgery within the past 6 months Use of steroids within the past 3 months, including prednisone, cortisone injections, inhaled steroids (topical steroids are acceptable) Use of anabolic steroids (testosterone, DHEA, DHEAS) or any growth promoters (growth hormone itself or analogs of growth hormone) in the past 12 months Liver function tests more than 3 times upper normal limits Undergoing intermittent ADT Uncontrolled thyroid disease (hyper- or hypo-thyroidism) Anemia, defined as hematocrit less than 38% Not physically capable of completing the tests

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 1<br>Participants receiving ADT and pioglitazone | Drug: Pioglitazone<br>* 45mg capsule, once daily for 1 year<br>* Other names: Actos;|
| 2<br>Participants receiving ADT only | |
| 3<br>Participants not receiving ADT and in remission from prostate cancer | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation for the development of incident diabetes |  | every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation for other cardiovascular risk factors, markers of inflammation and immunological changes |  | every 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hormone therapy