PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue

Phase 2

Completed

• Conditions: Healthy
• Interventions: Drug: Testosterone gel; Other: Placebo Testosterone gel; Drug: Depo-Medroxyprogesterone (DMPA); Drug: Dutasteride; Other: Placebo dutasteride; Other: Placebo DMPA

• Registration Number: NCT00490555
• Lead Sponsor: University of Washington

Brief Summary

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.

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 Timeline

• Study First Submitted: 2007-06-20
• Study First Submitted QC: 2007-06-21
• Study First Posted: 2007-06-22
• Study Start: 2009-01
• Primary Completion: 2012-01
• Study Completion: 2012-03
• Results First Submitted: 2013-06-19
• Status Verified: 2013-09
• Results First Submitted QC: 2013-09-12
• Last Update Submitted: 2013-09-12
• Results First Posted: 2013-11-15
• Last Update Posted: 2013-11-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 32

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4	Testosterone gel	Testosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
4	Depo-Medroxyprogesterone (DMPA)	Testosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
4	Placebo dutasteride	Testosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
1	Placebo dutasteride	Placebo gel + Placebo pill + placebo injection
1	Placebo DMPA	Placebo gel + Placebo pill + placebo injection
1	Placebo Testosterone gel	Placebo gel + Placebo pill + placebo injection
2	Testosterone gel	Testosterone 1% transdermal gel 10 g + placebo pill + placebo injection
3	Testosterone gel	Testosterone 1% transdermal gel 10 g + dutasteride 0.5 mg Orally + placebo injection
3	Dutasteride	Testosterone 1% transdermal gel 10 g + dutasteride 0.5 mg Orally + placebo injection

Primary Outcome Measures

Name	Time	Method
Testosterone Concentration	10 weeks
Prostate-specific Antigen (PSA)	10 weeks	PSA level week 10 end of treatment
Dihydrotestosterone (DHT) Concentration	10 weeks

Secondary Outcome Measures

Name	Time	Method
Androstenedione (AED)	10 weeks
Dehydroepiandrosterone (DHEA)	10 weeks

Trial Locations

Locations (1)

University of Washington; 🇺🇸 Seattle, Washington, United States