The Effects of Testosterone on Prostate Tissue (ACYP-1)

NCT ID: NCT00161486

Last Updated: 2008-09-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-07-31

Study Completion Date

2004-11-30

Brief Summary

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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 contraceptive and may impact the development of androgen replacement therapy in older men.

Detailed Description

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We will be administering two drugs: Testim (testosterone gel) and Acyline. Acyline is an experimental drug. 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.

Acyline 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. Therefore, Acyline blocks testosterone production. In preliminary studies, a single injection of Acyline reversibly lowered the FSH, LH and testosterone levels in the blood for approximately 15 days. Prolonged low levels of LH and FSH cause suppression of sperm production in normal men. However, men may experience some side effects from the low levels of testosterone caused by acyline, thus exogenous testosterone is required to sustain normal male androgen and organ effects without suppressing spermatogenesis. This combination of drugs is a promising male contraceptive regimen. In addition, millions of older men are using testosterone replacement to treat male "andropause"; low level testosterone associated with aging. However, the effect of testosterone on the prostate is unknown. Studies examining the effect of testosterone on the prostate are needed.

Conditions

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Hypogonadism Contraception

Keywords

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Male contraception Prostate Acyline Androgen replacement

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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1

Placebo acyline injections every two weeks (2 doses) + placebo testosterone gel daily for 4 weeks

Group Type PLACEBO_COMPARATOR

Placebo acyline

Intervention Type DRUG

Placebo acyline injections every two weeks (2 doses)

Placebo Testosterone gel

Intervention Type DRUG

placebo testosterone gel daily for 4 weeks

2

Acyline 300 μg/kg every two weeks (2 doses) + placebo Testosterone gel daily for 4 weeks

Group Type ACTIVE_COMPARATOR

Acyline

Intervention Type DRUG

Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks

Placebo Testosterone gel

Intervention Type DRUG

placebo testosterone gel daily for 4 weeks

3

Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks + Testosterone gel 100 mg daily for 4 weeks

Group Type ACTIVE_COMPARATOR

Testosterone gel

Intervention Type DRUG

Testosterone gel 100 mg daily for 4 weeks

Acyline

Intervention Type DRUG

Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks

Interventions

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Testosterone gel

Testosterone gel 100 mg daily for 4 weeks

Intervention Type DRUG

Acyline

Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks

Intervention Type DRUG

Placebo acyline

Placebo acyline injections every two weeks (2 doses)

Intervention Type DRUG

Placebo Testosterone gel

placebo testosterone gel daily for 4 weeks

Intervention Type DRUG

Other Intervention Names

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Testim

Eligibility Criteria

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Inclusion Criteria

* Males between 35 and 55, normal serum testosterone levels, normal gonadal function

Exclusion Criteria

* History of prostate cancer, PSA\>2.0, AUA BPH symptom score \>10, History of testosterone or anabolic steroid use, chronic medical illness or prostate disease, active serious infection or immunosuppression, history of a bleeding disorder or need for anticoagulation, abnormal digital rectal exam, abnormal prostate ultrasound, first degree relative with history of prostate cancer
Minimum Eligible Age

35 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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

NIH

Sponsor Role collaborator

University of Washington

OTHER

Sponsor Role lead

Responsible Party

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University of Washington

Principal Investigators

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William J Bremner, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

Locations

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University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

References

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Bhasin S, Singh AB, Mac RP, Carter B, Lee MI, Cunningham GR. Managing the risks of prostate disease during testosterone replacement therapy in older men: recommendations for a standardized monitoring plan. J Androl. 2003 May-Jun;24(3):299-311. doi: 10.1002/j.1939-4640.2003.tb02676.x. No abstract available.

Reference Type BACKGROUND
PMID: 12721204 (View on PubMed)

Morgentaler A, Bruning CO 3rd, DeWolf WC. Occult prostate cancer in men with low serum testosterone levels. JAMA. 1996 Dec 18;276(23):1904-6.

Reference Type BACKGROUND
PMID: 8968017 (View on PubMed)

Schatzl G, Madersbacher S, Thurridl T, Waldmuller J, Kramer G, Haitel A, Marberger M. High-grade prostate cancer is associated with low serum testosterone levels. Prostate. 2001 Apr;47(1):52-8. doi: 10.1002/pros.1046.

Reference Type BACKGROUND
PMID: 11304729 (View on PubMed)

Nelson PS, Clegg N, Arnold H, Ferguson C, Bonham M, White J, Hood L, Lin B. The program of androgen-responsive genes in neoplastic prostate epithelium. Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11890-5. doi: 10.1073/pnas.182376299. Epub 2002 Aug 16.

Reference Type BACKGROUND
PMID: 12185249 (View on PubMed)

Herbst KL, Anawalt BD, Amory JK, Bremner WJ. Acyline: the first study in humans of a potent, new gonadotropin-releasing hormone antagonist. J Clin Endocrinol Metab. 2002 Jul;87(7):3215-20. doi: 10.1210/jcem.87.7.8675.

Reference Type BACKGROUND
PMID: 12107227 (View on PubMed)

Bagatell CJ, Matsumoto AM, Christensen RB, Rivier JE, Bremner WJ. Comparison of a gonadotropin releasing-hormone antagonist plus testosterone (T) versus T alone as potential male contraceptive regimens. J Clin Endocrinol Metab. 1993 Aug;77(2):427-32. doi: 10.1210/jcem.77.2.8345047.

Reference Type BACKGROUND
PMID: 8345047 (View on PubMed)

Swerdloff RS, Bagatell CJ, Wang C, Anawalt BD, Berman N, Steiner B, Bremner WJ. Suppression of spermatogenesis in man induced by Nal-Glu gonadotropin releasing hormone antagonist and testosterone enanthate (TE) is maintained by TE alone. J Clin Endocrinol Metab. 1998 Oct;83(10):3527-33. doi: 10.1210/jcem.83.10.5184.

Reference Type BACKGROUND
PMID: 9768659 (View on PubMed)

Tom L, Bhasin S, Salameh W, Steiner B, Peterson M, Sokol RZ, Rivier J, Vale W, Swerdloff RS. Induction of azoospermia in normal men with combined Nal-Glu gonadotropin-releasing hormone antagonist and testosterone enanthate. J Clin Endocrinol Metab. 1992 Aug;75(2):476-83. doi: 10.1210/jcem.75.2.1639948.

Reference Type BACKGROUND
PMID: 1639948 (View on PubMed)

Page ST, Plymate SR, Bremner WJ, Matsumoto AM, Hess DL, Lin DW, Amory JK, Nelson PS, Wu JD. Effect of medical castration on CD4+ CD25+ T cells, CD8+ T cell IFN-gamma expression, and NK cells: a physiological role for testosterone and/or its metabolites. Am J Physiol Endocrinol Metab. 2006 May;290(5):E856-63. doi: 10.1152/ajpendo.00484.2005. Epub 2005 Dec 13.

Reference Type RESULT
PMID: 16352669 (View on PubMed)

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.

Reference Type RESULT
PMID: 16882745 (View on PubMed)

Mostaghel EA, Page ST, Lin DW, Fazli L, Coleman IM, True LD, Knudsen B, Hess DL, Nelson CC, Matsumoto AM, Bremner WJ, Gleave ME, Nelson PS. Intraprostatic androgens and androgen-regulated gene expression persist after testosterone suppression: therapeutic implications for castration-resistant prostate cancer. Cancer Res. 2007 May 15;67(10):5033-41. doi: 10.1158/0008-5472.CAN-06-3332.

Reference Type RESULT
PMID: 17510436 (View on PubMed)

Other Identifiers

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U 54 HD42454

Identifier Type: -

Identifier Source: secondary_id

03-9401-B

Identifier Type: -

Identifier Source: org_study_id