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PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue

Sponsor
University of Washington (Other)
Overall Status
Completed
CT.gov ID
NCT00490555
Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
32
Enrollment
1
Location
4
Arms
37.9
Duration (Months)
0.8
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Testosterone gel
  • Drug: Dutasteride
  • Drug: Depo-Medroxyprogesterone (DMPA)
  • Other: Placebo Testosterone gel
  • Other: Placebo dutasteride
  • Other: Placebo DMPA
 Phase 2/Phase 3

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 Design

Study Type:
Interventional
Actual Enrollment :
32 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
The Effect of Male Hormonal Contraceptive Regimens on Prostate Tissue In Normal Men
Study Start Date :
Jan 1, 2009
Actual Primary Completion Date :
Jan 1, 2012
Actual Study Completion Date :
Mar 1, 2012

Arms and Interventions

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)

    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

    • Other: Placebo dutasteride
    placebo pill for 12 weeks

    Outcome Measures

    Primary Outcome Measures

    1. Prostate-specific Antigen (PSA) [10 weeks]

      PSA level week 10 end of treatment

    2. Testosterone Concentration [10 weeks]

    3. Dihydrotestosterone (DHT) Concentration [10 weeks]

    Secondary Outcome Measures

    1. Androstenedione (AED) [10 weeks]

    2. Dehydroepiandrosterone (DHEA) [10 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    25 Years to 55 Years
    Sexes 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.

    • 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

    Locations

    Site City State Country Postal Code
    1 University of Washington Seattle Washington United States 98195

    Sponsors and Collaborators

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

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Stephanie T. Page, Associate Professor, University of Washington
    ClinicalTrials.gov Identifier:
    NCT00490555
    Other Study ID Numbers:
    • 31434-A
    • RFA-HD-06-014;
    • 06-4795-A 01
    First Posted:
    Jun 22, 2007
    Last Update Posted:
    Nov 15, 2013
    Last Verified:
    Sep 1, 2013
    Keywords provided by Stephanie T. Page, Associate Professor, University of Washington
    Male Contraception
    Testosterone
    Testis
    Contraception
    Prostate
    Additional relevant MeSH terms:
    Methyltestosterone
    Medroxyprogesterone Acetate
    Medroxyprogesterone
    Testosterone
    Testosterone undecanoate
    Testosterone enanthate
    Testosterone 17 beta-cypionate
    Dutasteride

    Study Results

    Participant Flow

    Recruitment Details Healthy male volunteers, 25-55 yr old, were recruited via advertisement: flyers on University campus and newspaper ads.
    Pre-assignment Detail
    Arm/Group Title 1) Placebo 2) Testosterone (T) Gel 3) T Gel+Dutasteride 4) T Gel+DMPA
    Arm/Group Description Placebo gel + Placebo pill + placebo DMPA Testosterone 1% transdermal gel 10g (Testim)+ placebo pill, daily + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g, daily + placebo Dutasteride pill, daily + DMPA 300mg injection (IM)
    Period Title: Overall Study
    STARTED 8 8 9 7
    COMPLETED 8 8 7 7
    NOT COMPLETED 0 0 2 0

    Baseline Characteristics

    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA Total
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM) Total of all reporting groups
    Overall Participants 8 8 9 7 32
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    8
    100%
    8
    100%
    9
    100%
    7
    100%
    32
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    41
    (7.72)
    37
    (6.19)
    37
    (8.45)
    39
    (10.11)
    39
    (3.46)
    Sex/Gender, Customized (participants) [Number]
    Female
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Male
    8
    100%
    8
    100%
    9
    100%
    7
    100%
    32
    100%
    Region of Enrollment (participants) [Number]
    United States
    8
    100%
    8
    100%
    9
    100%
    7
    100%
    32
    100%
    Luteinizing Hormone (LH) (IU/liter) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [IU/liter]
    4.0
    3.9
    5.3
    3.2
    4.1
    Follical-stimulating hormone (FSH) (IU/liter) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [IU/liter]
    3.6
    3.3
    4.0
    2.8
    3.4
    SHBG (nmol/liter) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [nmol/liter]
    33
    36
    38
    33
    35
    Testosterone (T) concentration (ng/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ng/mL]
    3.9
    3.9
    4.8
    4.0
    4.1
    Dihydrotestosterone (DHT) (ng/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ng/mL]
    0.5
    0.6
    0.7
    0.6
    0.6
    Prostate-Specific Antigen (PSA) (ng/mL) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ng/mL]
    0.7
    0.7
    0.9
    0.5
    0.7
    Prostate volume (ml) [Median (Inter-Quartile Range) ]
    Median (Inter-Quartile Range) [ml]
    25
    15
    15
    19
    18

    Outcome Measures

    1. Primary Outcome
    Title Prostate-specific Antigen (PSA)
    Description PSA level week 10 end of treatment
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    Measure Participants 8 7 7 7
    Median (Inter-Quartile Range) [ng/mL]
    0.8
    0.9
    0.7
    0.4
    2. Primary Outcome
    Title Testosterone Concentration
    Description
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    Measure Participants 8 7 7 7
    Median (Inter-Quartile Range) [ng/mL]
    4.0
    4.4
    7.0
    1.8
    3. Primary Outcome
    Title Dihydrotestosterone (DHT) Concentration
    Description
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    Measure Participants 8 7 7 7
    Median (Inter-Quartile Range) [ng/mL]
    0.5
    1.8
    0.5
    0.6
    4. Secondary Outcome
    Title Androstenedione (AED)
    Description
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    Measure Participants 8 7 7 7
    Median (Inter-Quartile Range) [ng/mL]
    0.9
    0.9
    1.8
    0.7
    5. Secondary Outcome
    Title Dehydroepiandrosterone (DHEA)
    Description
    Time Frame 10 weeks

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    Measure Participants 8 7 7 7
    Median (Inter-Quartile Range) [ng/mL]
    4.3
    3.5
    3.8
    3.2

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title 1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Arm/Group Description Placebo Testosterone gel + Placebo Dutasteride pill + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + placebo DMPA Testosterone 1% transdermal gel 10g + dutasteride 0.5mg Orally + placebo DMPA Testosterone 1% transdermal gel 10g + placebo Dutasteride + DMPA 300mg injection (IM)
    All Cause Mortality
    1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/8 (0%) 0/7 (0%) 0/9 (0%) 0/7 (0%)
    Other (Not Including Serious) Adverse Events
    1) Placebo 2) Testosterone Gel 3) T Gel +Dutasteride 4) T Gel+ DMPA
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 1/8 (12.5%) 2/7 (28.6%) 1/9 (11.1%) 1/7 (14.3%)
    General disorders
    Fatigue 1/8 (12.5%) 1 0/7 (0%) 0 0/9 (0%) 0 0/7 (0%) 0
    headache 0/8 (0%) 0 1/7 (14.3%) 1 0/9 (0%) 0 1/7 (14.3%) 1
    Skin and subcutaneous tissue disorders
    rash 0/8 (0%) 0 1/7 (14.3%) 1 0/9 (0%) 0 0/7 (0%) 0
    abscess 0/8 (0%) 0 0/7 (0%) 0 1/9 (11.1%) 1 0/7 (0%) 0

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Stephanie Page
    Organization University of Washington
    Phone 2066160483
    Email page@u.washington.edu
    Responsible Party:
    Stephanie T. Page, Associate Professor, University of Washington
    ClinicalTrials.gov Identifier:
    NCT00490555
    Other Study ID Numbers:
    • 31434-A
    • RFA-HD-06-014;
    • 06-4795-A 01
    First Posted:
    Jun 22, 2007
    Last Update Posted:
    Nov 15, 2013
    Last Verified:
    Sep 1, 2013