Dose Response Effects of Exogenous Testosterone on the Prostate and Comparison With Effects on Body Composition (Short Title: PROS-2)
Overview
- Phase
- Phase 2
- Intervention
- Testosterone 1% gel 2.5 g
- Conditions
- Healthy
- Sponsor
- University of Washington
- Enrollment
- 62
- Locations
- 1
- Primary Endpoint
- Serum Testosterone
- Status
- Completed
- Last Updated
- 8 years ago
Overview
Brief Summary
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
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.
Investigators
Stephanie T. Page
Professor Department of Medicine, Division of Metabolism, Endocrinology and Nutrition
University of Washington
Eligibility Criteria
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
Arms & Interventions
Arm 3: 2.5g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks
Intervention: Testosterone 1% gel 2.5 g
Arm 1: Placebo
Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks
Intervention: placebo acyline
Arm 1: Placebo
Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks
Intervention: placebo gel
Arm 2:1.25g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks
Intervention: Testosterone 1% gel 1.25 g
Arm 2:1.25g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks
Intervention: Acyline
Arm 3: 2.5g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks
Intervention: Acyline
Arm 4: 5g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks
Intervention: Testosterone 1% gel 5.0 g
Arm 4: 5g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks
Intervention: Acyline
Arm 5: 10g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks
Intervention: testosterone 1% gel 10 g
Arm 5: 10g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks
Intervention: Acyline
Arm 6: 15g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks
Intervention: testosterone 1% gel 15 g
Arm 6: 15g Testosterone
Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks
Intervention: Acyline
Outcomes
Primary Outcomes
Serum Testosterone
Time Frame: 12 weeks
Dihydrotestosterone (DHT)
Time Frame: 12 weeks
Prostate Tissue Testosterone Concentrations After Treatment
Time Frame: 12 weeks
To measure intraprostatic testosterone levels
Prostate Tissue DHT Concentrations After Treatment
Time Frame: 12 weeks
To measure intraprostatic dihydrotestosterone \[DHT\] levels
Secondary Outcomes
- Prostate Specific Antigen(12 weeks)
- Prostate Volume(12 weeks)
- International Prostate Symptom Score (IPSS)(12 weeks)