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

University of Washington

Status and phase: Completed; Phase 3; Phase 2

Conditions: Healthy

Treatments: Drug: testosterone 1% gel 15 g; Other: placebo acyline; Other: placebo gel; Drug: Testosterone 1% gel 5.0 g; Drug: Testosterone 1% gel 2.5 g; Drug: testosterone 1% gel 10 g; Drug: Testosterone 1% gel 1.25 g; Drug: Acyline

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01327495

39738

1R01AG037603-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 62 patients

Sex: Male

Ages: 25 to 55 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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62 participants in 6 patient groups, including a placebo group

Arm 1: Placebo

Placebo Comparator group

Description:

Placebo acyline every 2 weeks for two weeks + daily placebo gel x 12 weeks

Treatment:

Other: placebo gel

Other: placebo acyline

Arm 2:1.25g Testosterone

Active Comparator group

Description:

Acyline (300µg/kg every two weeks) + testosterone 1% gel 1.25 g daily x 12 weeks

Treatment:

Drug: Acyline

Drug: Testosterone 1% gel 1.25 g

Arm 3: 2.5g Testosterone

Active Comparator group

Description:

Acyline (300µg/kg every two weeks) + testosterone 1% gel 2.5 g daily x 12 weeks

Treatment:

Drug: Acyline

Drug: Testosterone 1% gel 2.5 g

Arm 4: 5g Testosterone

Active Comparator group

Description:

Acyline (300µg/kg every two weeks) + testosterone 1% gel 5.0 g daily x 12 weeks

Treatment:

Drug: Acyline

Drug: Testosterone 1% gel 5.0 g

Arm 5: 10g Testosterone

Active Comparator group

Description:

Acyline (300µg/kg every two weeks) + testosterone 1% gel 10 g daily x 12 weeks

Treatment:

Drug: Acyline

Drug: testosterone 1% gel 10 g

Arm 6: 15g Testosterone

Active Comparator group

Description:

Acyline (300µg/kg every two weeks) + testosterone 1% gel 15 g daily x 12 weeks

Treatment:

Drug: Acyline

Drug: testosterone 1% gel 15 g