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

Contraception Clinical Trial

— ACYP-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00161486
• Other study ID #: 03-9401-B
• Secondary ID: U 54 HD42454
• Status: Completed
• Phase: Phase 1
• First received: September 8, 2005
• Last updated: September 18, 2008
• Start date: July 2004
• Est. completion date: November 2004

Study information

• Verified date: September 2008
• Source: University of Washington
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: November 2004
• Est. primary completion date: November 2004
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 35 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Contraception
• Hypogonadism

Intervention

Drug:
• Testosterone gel
Testosterone gel 100 mg daily for 4 weeks
• Acyline
Acyline 300 µg/kg every two weeks (2 doses) for 4 weeks
• Placebo acyline
Placebo acyline injections every two weeks (2 doses)
• Placebo Testosterone gel
placebo testosterone gel daily for 4 weeks

Locations

Country	Name	City	State
United States	University of Washington	Seattle	Washington

Sponsors (2)

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

Country where clinical trial is conducted

United States, 

References & Publications (11)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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. — View Citation

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. — View Citation

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. A — View Citation

Schatzl G, Madersbacher S, Thurridl T, Waldmüller 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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Intervention trial to examine the hormonal regulation of prostate gene expression and tissue hormone levels, tissue protein expression and apoptosis.		28-days	No
Secondary	Cellular immune function		28-days	No

External Links

•   http://depts.washington.edu/popctr