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HealthyPhase 2/3PROS-1NCT00490555

PROS-1-Male Hormonal Contraceptive Regimens on Prostate Tissue

A Phase 2/3 study testing Testosterone gel, Dutasteride and Depo-Medroxyprogesterone (DMPA) in people with Healthy, run by University of Washington at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 25 to 55 years, men onlyHealthy volunteers can take part
Conditions the study is for
Healthy
What is being tested?
Testosterone gel, Dutasteride and Depo-Medroxyprogesterone (DMPA)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
32 participants
Where
1 siteUnited States
Study dates
Jan 2009to Mar 2012
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 55 years
  • Men only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 15Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Washington

    Seattle, Washington, 98195

Other trials in United States

About this study

Official title: 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.

Read more

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.

Read the 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.

Conditions
Healthy
Being tested
Testosterone gel, Dutasteride, Depo-Medroxyprogesterone (DMPA), Placebo Testosterone gel, Placebo dutasteride
Keywords
Male Contraception, Testosterone, Testis, Contraception, Prostate

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Testosterone gelDrug

    Also called Testim

    Testosterone gel 10 g

  • DutasterideDrug

    Also called Avodart

    dutasteride 0.5 mg orally

  • Depo-Medroxyprogesterone (DMPA)Drug

    Also called Depo-Provera

    300 mg DMPA injection on Day 0 IM (into the muscle)

  • Placebo Testosterone gelOther

    Place gel applied daily for 12 weeks

  • Placebo dutasterideOther

    placebo pill for 12 weeks

  • Placebo DMPAOther

    placebo DMPA injection Once

Study groups in NCT00490555
Study groupRoleWhat they receive
1Placebo comparatorPlacebo gel + Placebo pill + placebo injection
Receives: Other: Placebo Testosterone gel; Other: Placebo dutasteride; Other: Placebo DMPA
2Active comparatorTestosterone 1% transdermal gel 10 g + placebo pill + placebo injection
Receives: Drug: Testosterone gel
3Active comparatorTestosterone 1% transdermal gel 10 g + dutasteride 0.5 mg Orally + placebo injection
Receives: Drug: Testosterone gel; Drug: Dutasteride
4Active comparatorTestosterone 1% transdermal gel 10 g + placebo pill + DMPA 300 mg injection (IM)
Receives: Drug: Testosterone gel; Drug: Depo-Medroxyprogesterone (DMPA); Other: Placebo dutasteride

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Prostate-specific Antigen (PSA)

    PSA level week 10 end of treatment

    Measured: 10 weeks

  2. Testosterone Concentration

    Measured: 10 weeks

  3. Dihydrotestosterone (DHT) Concentration

    Measured: 10 weeks

Secondary outcomes (2)
  1. Androstenedione (AED)

    Measured: 10 weeks

  2. Dehydroepiandrosterone (DHEA)

    Measured: 10 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2007 (estimated)
  2. Study startJan 2009
  3. Primary completionJan 2012
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00490555
Sponsor's protocol ID
31434-A
Other IDs
RFA-HD-06-014;, 06-4795-A 01
Acronym
PROS-1
Status last verified
Sep 2013
First submitted
20 Jun 2007
Last updated
15 Nov 2013
Data monitoring committee
No

Publications

  • Amory JK, Page ST, Bremner WJ. Drug insight: Recent advances in male hormonal contraception. Nat Clin Pract Endocrinol Metab. 2006 Jan;2(1):32-41. doi: 10.1038/ncpendmet0069.

    PubMed 16932251
  • Brady BM, Amory JK, Perheentupa A, Zitzmann M, Hay CJ, Apter D, Anderson RA, Bremner WJ, Pollanen P, Nieschlag E, Wu FC, Kersemaekers WM. A multicentre study investigating subcutaneous etonogestrel implants with injectable testosterone decanoate as a potential long-acting male contraceptive. Hum Reprod. 2006 Jan;21(1):285-94. doi: 10.1093/humrep/dei300. Epub 2005 Sep 19.

    PubMed 16172147
  • Burkman R, Schlesselman JJ, Zieman M. Safety concerns and health benefits associated with oral contraception. Am J Obstet Gynecol. 2004 Apr;190(4 Suppl):S5-22. doi: 10.1016/j.ajog.2004.01.061.

    PubMed 15105794
  • Jacobsen SJ, Girman CJ, Lieber MM. Natural history of benign prostatic hyperplasia. Urology. 2001 Dec;58(6 Suppl 1):5-16; discussion 16. doi: 10.1016/s0090-4295(01)01298-5.

    PubMed 11750242
  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.

    PubMed 17237035
  • Wilson JD, George FW. The Physiology of Reproduction. Raven Press, 1994

  • Russell DW, Wilson JD. Steroid 5 alpha-reductase: two genes/two enzymes. Annu Rev Biochem. 1994;63:25-61. doi: 10.1146/annurev.bi.63.070194.000325. No abstract available.

    PubMed 7979239
  • Thompson IM, Goodman PJ, Tangen CM, Lucia MS, Miller GJ, Ford LG, Lieber MM, Cespedes RD, Atkins JN, Lippman SM, Carlin SM, Ryan A, Szczepanek CM, Crowley JJ, Coltman CA Jr. The influence of finasteride on the development of prostate cancer. N Engl J Med. 2003 Jul 17;349(3):215-24. doi: 10.1056/NEJMoa030660. Epub 2003 Jun 24.

    PubMed 12824459
  • Geller J. Effect of finasteride, a 5 alpha-reductase inhibitor on prostate tissue androgens and prostate-specific antigen. J Clin Endocrinol Metab. 1990 Dec;71(6):1552-5. doi: 10.1210/jcem-71-6-1552.

    PubMed 1699965
  • Geller J, Albert J. Effects of castration compared with total androgen blockade on tissue dihydrotestosterone (DHT) concentration in benign prostatic hyperplasia (BPH). Urol Res. 1987;15(3):151-3. doi: 10.1007/BF00254427.

    PubMed 3629749
  • Mohler JL, Gregory CW, Ford OH 3rd, Kim D, Weaver CM, Petrusz P, Wilson EM, French FS. The androgen axis in recurrent prostate cancer. Clin Cancer Res. 2004 Jan 15;10(2):440-8. doi: 10.1158/1078-0432.ccr-1146-03.

    PubMed 14760063
  • Forti G, Salerno R, Moneti G, Zoppi S, Fiorelli G, Marinoni T, Natali A, Costantini A, Serio M, Martini L, et al. Three-month treatment with a long-acting gonadotropin-releasing hormone agonist of patients with benign prostatic hyperplasia: effects on tissue androgen concentration, 5 alpha-reductase activity and androgen receptor content. J Clin Endocrinol Metab. 1989 Feb;68(2):461-8. doi: 10.1210/jcem-68-2-461.

    PubMed 2465302
  • Habib FK, Ross M, Tate R, Chisholm GD. Differential effect of finasteride on the tissue androgen concentrations in benign prostatic hyperplasia. Clin Endocrinol (Oxf). 1997 Feb;46(2):137-44. doi: 10.1046/j.1365-2265.1997.950908.x.

    PubMed 9135694
  • Page ST, Lin DW, Mostaghel EA, Hess DL, True LD, Amory JK, Nelson PS, Matsumoto AM, Bremner WJ. Persistent intraprostatic androgen concentrations after medical castration in healthy men. J Clin Endocrinol Metab. 2006 Oct;91(10):3850-6. doi: 10.1210/jc.2006-0968. Epub 2006 Aug 1.

    PubMed 16882745
  • Page ST, Amory JK, Anawalt BD, Irwig MS, Brockenbrough AT, Matsumoto AM, Bremner WJ. Testosterone gel combined with depomedroxyprogesterone acetate is an effective male hormonal contraceptive regimen and is not enhanced by the addition of a GnRH antagonist. J Clin Endocrinol Metab. 2006 Nov;91(11):4374-80. doi: 10.1210/jc.2006-1411. Epub 2006 Aug 29.

    PubMed 16940442

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Testosterone gel, Dutasteride and Depo-Medroxyprogesterone (DMPA) in people with Healthy, run by University of Washington at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 15 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Prostate-specific Antigen (PSA) (time frame: 10 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00490555, which also lists 15 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Nov 2013.

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