Clinical trial NCT01327495: PROS-2 Dose Response Effects of Exogenous Testosterone on the Prostate
Official title: Dose Response Effects of Exogenous Testosterone on the Prostate and Comparison With Effects on Body Composition (Short Title: PROS-2)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Healthy
Keywords: Androgen replacement in men
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2011-04-01
Enrollment: 62
Sex: MALE
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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
* Weight \>320 pounds or BMI \> 40
* PSA Level \> 2.1

Primary outcomes:
measure: Prostate Tissue DHT Concentrations After Treatment
timeFrame: 12 weeks
measure: Serum Testosterone
timeFrame: 12 weeks
measure: Dihydrotestosterone (DHT)
timeFrame: 12 weeks
measure: Prostate Tissue Testosterone Concentrations After Treatment
timeFrame: 12 weeks
Secondary outcomes:
measure: Prostate Specific Antigen
timeFrame: 12 weeks
measure: Prostate Volume
timeFrame: 12 weeks
measure: International Prostate Symptom Score (IPSS)
timeFrame: 12 weeks
Other outcomes:
measure: 17-OHPreg
timeFrame: 12 weeks
measure: 17-OHP
timeFrame: 12 weeks
measure: Androstenedione
timeFrame: 12 weeks
measure: Androsterone
timeFrame: 12 weeks
measure: DHEA
timeFrame: 12 weeks
measure: Pregnenolone
timeFrame: 12 weeks
measure: Progesterone
timeFrame: 12 weeks
Locations:
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of Washington
name: Stephanie T Page, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thirumalai A, Cooper LA, Rubinow KB, Amory JK, Lin DW, Wright JL, Marck BT, Matsumoto AM, Page ST. Stable Intraprostatic Dihydrotestosterone in Healthy Medically Castrate Men Treated With Exogenous Testosterone. J Clin Endocrinol Metab. 2016 Jul;101(7):2937-44. doi: 10.1210/jc.2016-1483. Epub 2016 May 12.