PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue (PROS-1)

September 12, 2013 updated by: Stephanie T. Page, University of Washington

The Effect of Male Hormonal Contraceptive Regimens on Prostate Tissue In Normal Men

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

32

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

25 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Men in good health, and without a history of chronic androgen therapy or known history of gonadal or prostate abnormalities.

    • PSA ≤ 2.
    • Age 25-55 years
    • Ability to understand the study,study procedures and provide consent
    • Normal serum total T, LH, FSH, urine analyses, and sperm count > or equal to 15million/ml
    • International Prostate Symptom Score (IPSS) < 10
    • Normal seminal fluid analysis (>20 million sperm/ml)
    • Agree not to donate blood during the treatment and recovery periods

Exclusion Criteria:

  • A history or evidence of prostate or breast cancer
  • History of invasive therapy for BPH
  • History of acute urinary retention
  • Current or past treatment with a 5α-reductase inhibitor
  • History of anti/androgenic drugs or drugs that interfere with steroid metabolism within past 3 months
  • Severe systemic illness (renal, liver, cardiac, lung disease, cancer, poorly controlled diabetes)
  • Known untreated obstructive sleep apnea
  • Hematocrit > 52%
  • Skin disease that might interfere with T gel absorption
  • Hypersensitivity to any of the drugs used in the study
  • History of a bleeding disorder or anticoagulation
  • History of drug or alcohol abuse within 12 months
  • History of infertility or desire for fertility within 12 months, or current pregnant partner
  • A first-degree relative (i.e. father, brother) with a history of prostate cancer
  • Abnormal digital rectal examination or prostate ultrasound

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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 Names:
  • Testim
Drug: Dutasteride
dutasteride 0.5 mg orally
Other Names:
  • Avodart
Active Comparator: 4
Testosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
Other: Placebo dutasteride
placebo pill for 12 weeks
Drug: Testosterone gel
Testosterone gel 10 g
Other Names:
  • Testim
Drug: Depo-Medroxyprogesterone (DMPA)
300 mg DMPA injection on Day 0 IM (into the muscle)
Other Names:
  • Depo-Provera

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Prostate-specific Antigen (PSA)
Time Frame: 10 weeks
PSA level week 10 end of treatment
10 weeks
Testosterone Concentration
Time Frame: 10 weeks
10 weeks
Dihydrotestosterone (DHT) Concentration
Time Frame: 10 weeks
10 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Androstenedione (AED)
Time Frame: 10 weeks
10 weeks
Dehydroepiandrosterone (DHEA)
Time Frame: 10 weeks
10 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Stephanie T Page, MD, PhD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2009

Primary Completion (Actual)

January 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

June 20, 2007

First Submitted That Met QC Criteria

June 21, 2007

First Posted (Estimate)

June 22, 2007

Study Record Updates

Last Update Posted (Estimate)

November 15, 2013

Last Update Submitted That Met QC Criteria

September 12, 2013

Last Verified

September 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 31434-A
  • RFA-HD-06-014;
  • 06-4795-A 01 (Other Identifier: University of Washington IRB (old application number))

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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