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| Sponsor: | University of Washington |
|---|---|
| Collaborator: |
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) |
| Information provided by: | University of Washington |
| ClinicalTrials.gov Identifier: | NCT00490555 |
Purpose
The investigators propose to examine the in vivo responses to hormonal manipulation at the molecular level directly in the tissue of interest (prostate). As in the investigators' previous, pilot study, the investigators will use the novel approach of procuring tissue specimens from normal, healthy men who might be chose to use a male hormonal contraceptive regimen were it available. The investigators will employ state of the art techniques such as laser capture microdissection (LCM) and cDNA microarrays to determine the tissue-specific consequences of male hormonal contraceptive regimens on the prostate. The results will help guide the design, safety monitoring, and selection of male hormonal contraceptive agents and provide valuable insights into prostate human prostate biology.
The investigators will test the hypothesis that exogenous T administration that results in increased circulating T and dihydrotestosterone (DHT) levels will increase intraprostatic concentrations of T and its metabolite DHT.
The investigators will test the hypothesis that the addition of a potent 5α-reductase inhibitor, dutasteride, or the progestin, Depomedoxyprogesterone (IM DMPA), to T administration in young and middle aged men will decrease intraprostatic DHT and increase intraprostatic T concentrations compared to T alone.
The investigators will test the hypothesis that the addition of a 5α-reductase inhibitor dutasteride or the progestin IM DMPA to exogenous T, by reducing intraprostatic DHT, will decrease prostate epithelial proliferation, assessed by Ki-67 labeling index (Ki-67LI), and increase apoptosis, assessed by caspase-3 expression, and decrease androgen-regulated protein expression such as prostate specific antigen (PSA).
The investigators will test the hypothesis that the addition of a 5α-reductase inhibitor or the progestin IM DMPA to exogenous T, by modifying the intraprostatic hormonal milieu, will alter prostate epithelial gene expression. Specifically, the investigators expect that the addition of the 5α-reductase inhibitor dutasteride or the progestin IM DMPA to exogenous T, will result in decreased expression of androgen-regulated genes such as PSA.
| Condition | Intervention | Phase |
|---|---|---|
|
Healthy |
Drug: Testosterone gel Drug: Dutasteride Drug: Depo-Medroxyprogesterone (DMPA) Other: Placebo Testosterone gel Other: Placebo dutasteride Other: Placebo DMPA |
Phase II Phase III |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Pharmacokinetics/Dynamics Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| Official Title: | The Effect of Male Hormonal Contraceptive Regimens on Prostate Tissue In Normal Men |
| Estimated Enrollment: | 48 |
| Study Start Date: | January 2009 |
| Estimated Study Completion Date: | January 2012 |
| Estimated Primary Completion Date: | January 2012 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Placebo Comparator: 1
Placebo gel + Placebo pill + placebo injection
|
Other: Placebo Testosterone gel
Place gel applied daily for 12 weeks
Other: Placebo dutasteride
placebo pill for 12 weeks
Other: Placebo DMPA
placebo DMPA injection Once
|
|
Active Comparator: 2
Testosterone 1% transdermal gel 10 g + placebo pill + placebo injection
|
Drug: Testosterone gel
Testosterone gel 10 g
Other Name: Testim
|
|
Active Comparator: 3
Testosterone 1% transdermal gel 10 g + dutasteride 0.5 mg Orally + placebo injection
|
Drug: Testosterone gel
Testosterone gel 10 g
Other Name: Testim
Drug: Dutasteride
dutasteride 0.5 mg orally
Other Name: Avodart
|
|
Active Comparator: 4
Testosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
|
Drug: Testosterone gel
Testosterone gel 10 g
Other Name: Testim
Drug: Depo-Medroxyprogesterone (DMPA)
300 mg DMPA injection on Day 0 IM (into the muscle)
Other Name: Depo-Provera
Other: Placebo dutasteride
placebo pill for 12 weeks
|
The purpose of this research study is to understand the effects of testosterone on the prostate. This knowledge will be used to help in the development of a safe male hormonal contraception.
We will be administering three drugs in this study: Testim (testosterone (T) gel), dutasteride (which affects testosterone break down) and Depomedoxyprogesterone (DMPA, a progestin). We want to see their effects on levels of hormones in the blood and prostate. In addition, we will be examining the effects of these drugs on the expression of genes within the prostate. DMPA suppresses LH and FSH, which are hormones made by the pituitary gland, thus blocking the signal from the brain that causes the testes to make testosterone. Prolonged (> 1 month) low levels of LH and FSH cause decreased sperm production in normal men. However, men may experience some side effects from the low levels of testosterone caused by DMPA; adding testosterone to DMPA eliminates these side effects while more effectively blocking LH and FSH release and sperm production. This combination of drugs is a promising male contraceptive regimen. However, the effect of these drugs on the prostate is not known. Some studies suggest that testosterone administration may promote prostate growth. Dutasteride blocks the conversion of testosterone to dihydrotestosterone and is used to treat men with enlarged prostates. Dutasteride shrinks the prostate. It is possible that combining testosterone and dutasteride may be an effective part of a male hormonal contraceptive regime. Therefore, further studies examining the effect of testosterone, DMPA and dutasteride on the prostate are needed.
Eligibility| Ages Eligible for Study: | 25 Years to 55 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Men in good health, and without a history of chronic androgen therapy or known history of gonadal or prostate abnormalities.
Exclusion Criteria:
Contacts and Locations| United States, Washington | |
| University of Washington | |
| Seattle, Washington, United States, 98195 | |
| Principal Investigator: | Stephanie T Page, MD, PhD | University of Washington |
More Information
| Responsible Party: | Stephanie T Page, MD, PhD, University of Washington |
| ClinicalTrials.gov Identifier: | NCT00490555 History of Changes |
| Other Study ID Numbers: | 31434-A, RFA-HD-06-014;, 06-4795-A 01 |
| Study First Received: | June 20, 2007 |
| Last Updated: | December 30, 2010 |
| Health Authority: | United States: Food and Drug Administration; United States: Institutional Review Board |
|
Male Contraception Testosterone Testis Contraception Prostate |
|
Testosterone Testosterone enanthate Testosterone undecanoate Testosterone 17 beta-cypionate Methyltestosterone Medroxyprogesterone Acetate Contraceptive Agents Medroxyprogesterone Dutasteride Androgens Hormones Hormones, Hormone Substitutes, and Hormone Antagonists Physiological Effects of Drugs |
Pharmacologic Actions Antineoplastic Agents, Hormonal Antineoplastic Agents Therapeutic Uses Anabolic Agents Reproductive Control Agents Contraceptive Agents, Male Contraceptive Agents, Female Contraceptives, Oral, Synthetic Contraceptives, Oral 5-alpha Reductase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |
