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

Sponsor:	University of Washington
Collaborator:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	University of Washington
ClinicalTrials.gov Identifier:	NCT00161486

Purpose

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.

Condition	Intervention	Phase
Hypogonadism Contraception	Drug: Testosterone gel Drug: Acyline Drug: Placebo acyline Drug: Placebo Testosterone gel	Phase I

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) Primary Purpose: Treatment
Official Title:	The Effects of Testosterone on Prostate Tissue in Normal Men (ACYP-1)

Resource links provided by NLM:

MedlinePlus related topics: Birth Control

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Acyline Oxymesterone Testosterone enanthate Testosterone undecanoate

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

Intervention trial to examine the hormonal regulation of prostate gene expression and tissue hormone levels, tissue protein expression and apoptosis. [ Time Frame: 28-days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Cellular immune function [ Time Frame: 28-days ] [ Designated as safety issue: No ]

Enrollment:	13
Study Start Date:	July 2004
Study Completion Date:	November 2004
Primary Completion Date:	November 2004 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: 1 Placebo acyline injections every two weeks (2 doses) + placebo testosterone gel daily for 4 weeks	Drug: Placebo acyline Placebo acyline injections every two weeks (2 doses) Drug: Placebo Testosterone gel placebo testosterone gel daily for 4 weeks
Active Comparator: 2 Acyline 300 μg/kg every two weeks (2 doses) + placebo Testosterone gel daily for 4 weeks	Drug: Acyline Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks Drug: Placebo Testosterone gel placebo testosterone gel daily for 4 weeks
Active Comparator: 3 Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks + Testosterone gel 100 mg daily for 4 weeks	Drug: Testosterone gel Testosterone gel 100 mg daily for 4 weeks Other Name: Testim Drug: Acyline Acyline 300 μg/kg every two weeks (2 doses) for 4 weeks

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	35 Years to 55 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00161486

Locations

United States, Washington
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:

William J Bremner, MD

University of Washington

More Information

Additional Information:

http://depts.washington.edu/popctr This link exits the ClinicalTrials.gov site

Publications:

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 of Testosterone and/or Its Metabolites. Am J Physiol Endocrinol Metab. 2005 Dec 13; [Epub ahead of print]

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. Epub 2006 Aug 1.

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.

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. Review. No abstract available.

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.

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.

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. Epub 2002 Aug 16.

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.

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.

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.

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.

Responsible Party:	William J Bremner, MD, PhD, University of Washington
ClinicalTrials.gov Identifier:	NCT00161486 History of Changes
Other Study ID Numbers:	03-9401-B, U 54 HD42454
Study First Received:	September 8, 2005
Last Updated:	September 18, 2008
Health Authority:	United States: Food and Drug Administration

Keywords provided by University of Washington:

Male contraception
Prostate
Acyline
Androgen replacement

Additional relevant MeSH terms:

Hypogonadism
Gonadal Disorders
Endocrine System Diseases
Testosterone
Testosterone enanthate
Testosterone undecanoate
Testosterone 17 beta-cypionate
Methyltestosterone
Androgens

Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Therapeutic Uses
Anabolic Agents

ClinicalTrials.gov processed this record on February 09, 2012