PROS-2 Dose Response Effects of Exogenous Testosterone on the Prostate

Study Overview
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Brief Summary
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The investigators will conduct a three-month, randomized, placebo-controlled trial comparing the effects of increasing doses of androgen supplementation with Testosterone (T) gel on the prostate in healthy men who are treated with acyline to block gonadal androgen production.

Detailed Description
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The investigators overall goals are (i) to determine the relationship between serum and prostate tissue hormone concentrations in men in response to increasing doses of exogenous androgens; (ii) to determine the impact that alterations in serum and tissue testosterone concentrations have on prostate epithelial cell function and phenotype; and (iii) to determine the relationships between prostatic androgens and alterations in the tissue microenvironment. The investigators will perform a study in healthy, middle-aged men to address the following Specific Aims: Specific Aims: To compare the dose-response relationships between serum testosterone and intraprostatic androgens and androgen action, and serum testosterone and anabolic activity in healthy, middle-aged men. Hypothesis: The investigators hypothesize that very low levels of serum testosterone will lower concentrations of intraprostatic testosterone and dihydrotestosterone (DHT). However, when serum testosterone concentrations are within or even above the normal range there will be no significant increases in intraprostatic testosterone and dihydrotestosterone. In contrast, the investigators expect that anabolic activity will increase with increasing concentrations of circulating testosterone. Secondarily, the investigators hypothesize that increasing levels of serum testosterone beyond the low normal range will have little impact on androgen action within the prostate. Approach: The investigators will conduct a randomized, placebo-controlled trial in healthy men who are medically castrated and administered one of five different doses of testosterone gel (Androgel) for 12 weeks.

Official Title
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Dose Response Effects of Exogenous Testosterone on the Prostate and Comparison With Effects on Body Composition (Short Title: PROS-2)

Conditions
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Healthy

Intervention / Treatment
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* Other: placebo acyline
* Other: placebo gel
* Drug: Testosterone 1% gel 1.25 g
* Drug: Testosterone 1% gel 2.5 g
* Drug: Testosterone 1% gel 5.0 g
* Drug: testosterone 1% gel 10 g
* Drug: testosterone 1% gel 15 g
* Drug: Acyline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In good health, without severe systemic illness (i.e., renal, liver, cardiac or lung disease, cancer, insulin dependent diabetes) Male between the ages of 25 and 55 years old Able to understand and comply with protocol instructions and requirements International Prostate Symptom Score (IPSS) <11 Agrees to not donate blood during the study Normal serum total T, LH, FSH, urine analysis, COMP, CBC and sperm count Exclusion Criteria: History of, or current breast cancer or prostate cancer Clinically significant findings on digital rectal exam such as nodules, areas of induration or any other malignancy or abnormal prostate ultrasound History of invasive therapy for BPH Current or past treatment with a 5α-reductase inhibitor History of drug or alcohol abuse within the past 12 months History of a bleeding disorder or anticoagulation Skin disease that might interfere with T-gel absorption Participation in another drug study in the past 3 months A first-degree relative (i.e. father, brother) with a history of prostate cancer History of infertility or desire for fertility within 6 months, or current pregnant female partner Weight >320 pounds or BMI > 40 PSA Level > 2.1

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Arm 1: Placebo<br>Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks | Other: placebo acyline<br>* Placebo acyline subcutaneous injection every 2 weeks<br>* Other names: placebo;Other: placebo gel<br>* daily placebo testosterone gel applied transdermally x 12 weeks<br>* Other names: placebo;|
| Active Comparator: Arm 2:1.25g Testosterone<br>Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks | Drug: Testosterone 1% gel 1.25 g<br>* testosterone 1% gel 1.25 g daily applied transdermally x 12 weeks<br>* Other names: Androgel;Drug: Acyline<br>* 300 ug/kg subcutaneous injection every 2 weeks<br>* Other names: GNRH antagonist;|
| Active Comparator: Arm 3: 2.5g Testosterone<br>Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks | Drug: Testosterone 1% gel 2.5 g<br>* Testosterone 1% gel 2.5 g daily applied transdermally x 12 weeks<br>* Other names: Androgel;Drug: Acyline<br>* 300 ug/kg subcutaneous injection every 2 weeks<br>* Other names: GNRH antagonist;|
| Active Comparator: Arm 4: 5g Testosterone<br>Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks | Drug: Testosterone 1% gel 5.0 g<br>* Testosterone 1% gel 5.0 g daily applied transdermally x 12 weeks<br>* Other names: Androgel;Drug: Acyline<br>* 300 ug/kg subcutaneous injection every 2 weeks<br>* Other names: GNRH antagonist;|
| Active Comparator: Arm 5: 10g Testosterone<br>Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks | Drug: testosterone 1% gel 10 g<br>* Testosterone 1% gel 10 g daily applied transdermally x 12 weeks<br>* Other names: Androgel;Drug: Acyline<br>* 300 ug/kg subcutaneous injection every 2 weeks<br>* Other names: GNRH antagonist;|
| Active Comparator: Arm 6: 15g Testosterone<br>Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks | Drug: testosterone 1% gel 15 g<br>* Testosterone 1% gel 15 g daily applied transdermally x 12 weeks<br>* Other names: Androgel;Drug: Acyline<br>* 300 ug/kg subcutaneous injection every 2 weeks<br>* Other names: GNRH antagonist;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate Tissue DHT Concentrations After Treatment | To measure intraprostatic dihydrotestosterone [DHT] levels | 12 weeks | 
| Serum Testosterone |  | 12 weeks | 
| Dihydrotestosterone (DHT) |  | 12 weeks | 
| Prostate Tissue Testosterone Concentrations After Treatment | To measure intraprostatic testosterone levels | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prostate Specific Antigen |  | 12 weeks | 
| Prostate Volume |  | 12 weeks | 
| International Prostate Symptom Score (IPSS) | IPSS score: 0-7 mildly symptomatic, 8-19 moderately symptomatic, 20-35 severely symptomatic | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Androgen replacement in men