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

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: placebo acyline; Other: placebo gel; Drug: Testosterone 1% gel 1.25 g; Drug: Acyline; 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

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.

• Study Type: Interventional
• Enrollment (Actual): 62
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Time Frame
17-OHPreg	12 weeks
17-OHP	12 weeks
Androstenedione	12 weeks
Androsterone	12 weeks
DHEA	12 weeks
Pregnenolone	12 weeks
Progesterone	12 weeks

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Institutes of Health (NIH); National Institute on Aging (NIA)
• Investigators: Principal Investigator: Stephanie T Page, MD, PhD, University of Washington

Publications and helpful links

General Publications

• 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.

Helpful Links

• Dedicated to basic and clinical research primarily focusing on the male reproductive system

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: March 21, 2011
• First Submitted That Met QC Criteria: March 31, 2011
• First Posted (Estimate): April 1, 2011

Study Record Updates

• Last Update Posted (Actual): October 5, 2017
• Last Update Submitted That Met QC Criteria: September 7, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Androgen replacement in men
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Hormone Antagonists; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Acyline
• Other Study ID Numbers: 39738; 1R01AG037603-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO