PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stephanie T. Page, University of Washington
ClinicalTrials.gov Identifier:
NCT00490555
First received: June 20, 2007
Last updated: September 12, 2013
Last verified: September 2013
  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 2
Phase 3

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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Prostate-specific Antigen (PSA) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
    PSA level week 10 end of treatment

  • Testosterone Concentration [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Dihydrotestosterone (DHT) Concentration [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Androstenedione (AED) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]
  • Dehydroepiandrosterone (DHEA) [ Time Frame: 10 weeks ] [ Designated as safety issue: No ]

Enrollment: 32
Study Start Date: January 2009
Study Completion Date: March 2012
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

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.

  Eligibility

Ages Eligible for Study:   25 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00490555

Locations
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Stephanie T Page, MD, PhD University of Washington
  More Information

Additional Information:
Publications:
Wilson JD, George FW. The Physiology of Reproduction. Raven Press, 1994

Responsible Party: Stephanie T. Page, Associate Professor, 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
Results First Received: June 19, 2013
Last Updated: September 12, 2013
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Washington:
Male Contraception
Testosterone
Testis
Contraception
Prostate

Additional relevant MeSH terms:
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
Contraceptives, Oral, Synthetic
Contraceptives, Oral
Contraceptive Agents, Female
Contraceptive Agents, Male
5-alpha Reductase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Urological Agents

ClinicalTrials.gov processed this record on August 20, 2014