HOP-3 Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone - 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:	NCT00839319

Purpose

The purpose of this investigational study is to determine how much male hormone, testosterone, is necessary to maintain sperm production in the testis. This knowledge will be used to help in the development of a safe male hormonal contraception.

Condition	Intervention	Phase
Healthy Males	Drug: Acyline Other: placebo hCG (no active ingredient) Drug: hCG (human chorionic gonadotropin) Drug: Testosterone gel	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Manipulation of the Intratesticular Hormonal Milieu With Exogenous Testosterone (Short Title (HOP-3)

Resource links provided by NLM:

Drug Information available for: Testosterone Propionate Methyltestosterone Testosterone Acyline Choriogonadotropin Alfa Oxymesterone Testosterone enanthate Testosterone undecanoate Chorionic gonadotropin

U.S. FDA Resources

Further study details as provided by University of Washington:

Primary Outcome Measures:

To clarify the dose-response relationship between low does of hCG and intratesticular testosterone [ Time Frame: 10-days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To determine whether physiologic does of exogenous testosterone contributes to intratesticular testosterone concentrations. [ Time Frame: 10-days ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	March 2009
Estimated Study Completion Date:	January 2011
Estimated Primary Completion Date:	November 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group 1: Experimental Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days	Drug: Acyline 300 ug/kg subcutaneous injections on Day 1. Other: placebo hCG (no active ingredient) placebo hCG
Group 2: Experimental Acyline 300 ug/kg (SQ) inj(s) on Day 1 plus subcutaneous 15 IU hCG injection (inj) every other day (5 doses) for 10 days	Drug: Acyline 300 ug/kg subcutaneous injections on Day 1. Drug: hCG (human chorionic gonadotropin) 15 IU subcutaneous injection every other day for 10 days (5 doses)
Group 3: Experimental Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 60 IU hCG injection (inj) every other day (5 doses) for 10 days	Drug: Acyline 300 ug/kg subcutaneous injections on Day 1. Drug: hCG (human chorionic gonadotropin) 60 IU subcutaneous injection
Group 4: Experimental Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous 125 IU hCG injection (inj) every other day (5 doses) for 10 days	Drug: Acyline 300 ug/kg subcutaneous injections on Day 1. Drug: hCG (human chorionic gonadotropin) 125 IU subcutaneous injection
Group 5: Experimental Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days	Drug: Acyline 300 ug/kg subcutaneous injections on Day 1. Drug: Testosterone gel 75 mg testosterone gel applied transdermally for 10 days

Detailed Description:

Three study drugs will be used in this study: Testim (testosterone gel), Human Chorionic Gonadotropin (hCG) and acyline. Testosterone is a naturally occurring hormone in men. When given to normal men, testosterone gel will temporarily lower the amount of testosterone in the testes and lower sperm counts. hCG is a female hormone produced during pregnancy that is similar to and has the same actions as a male hormone, luteinizing hormone (LH). Like LH, hCG stimulates the testis to produce testosterone and sperm, and is used in the treatment of men who are deficient in LH. When hCG is given together with testosterone to normal men, the amount of testosterone in the testes will change, dependent on the amount of hCG received. Some participants will receive placebo hCG injections (no active medication).

Acyline suppresses LH (luteinizing hormone) and FSH (follicle stimulating hormone), which are hormones made by the pituitary gland in the brain, thus blocking the signal from the brain that causes the testes to make testosterone. Therefore, acyline blocks testosterone production. Men may experience some side effects from the low levels of testosterone caused by acyline.

Acyline is an experimental drug. Testosterone gel and hCG are approved for use in men with low testosterone levels. The U.S. Food and Drug Administration (FDA) allows testosterone gel, hCG and acyline to be given in combination for research to a small number of volunteers. Over 125 men have received acyline. Both Acyline and hCG will be given by injection. Acyline injections are formulated by subjects weight and may be given in multiple injections.

Participation will last approximately 2 months. The study involves a minimum of 9 visits in Seattle, WA. Clinic visits at Screening, Day 1 and Day 10 will take about 1-1.5 hours each. On Day 1 & 10 a fine needle aspiration of one testis will be performed. The Day 7, Day 17, and Day 40 visits will take approximately 30 minutes. The other visits will take about 15 minutes each time. Over the course of the study, which includes 5 separate blood draws, approximately 12 ounces (one and a half cups) of blood will be drawn. Some of the study drugs will be given by injection. One drug is a topical gel.

This is NOT a trial of a male contraceptive, and the study medications will not prevent pregnancy. Subjects must use an acceptable form of birth control.

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Male
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Males age 18-50
Normal serum testosterone, LH and FSH
PSA < 4.0
Agrees not to donate blood or participate in another research study during the study
Informed consent
In general good health based on normal screening evaluation (consisting of a medical history, physical exam, normal sperm count, normal serum chemistry and hematology)
Must be willing to use a reliable form of contraception during the study

Exclusion Criteria:

Oligospermia (sperm count < 15 million/mL after 48 hours of abstinence) and/or abnormal motility or morphology.
Participation in a long-term male contraceptive study within the past three months
History of testosterone or anabolic steroid abuse in the past
Poor general health with significantly abnormal blood results
History of or current testicular disease
History of a bleeding disorder or need for anticoagulation
History of sleep apnea and/or major psychiatric problems
BMI > 32
Subjects with a skin condition that might interfere or be exacerbated by testosterone gel use
Subject's with alcohol or drug use

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00839319

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 Bremner, MD, PhD

University of Washington

More Information

Additional Information:

Dedicated to basic and clinical research focused primarily on the male reproductive system This link exits the ClinicalTrials.gov site

Publications:

[No authors listed] Contraceptive efficacy of testosterone-induced azoospermia in normal men. World Health Organization Task Force on methods for the regulation of male fertility. Lancet. 1990 Oct 20;336(8721):955-9.

Wu FC, Farley TM, Peregoudov A, Waites GM. Effects of testosterone enanthate in normal men: experience from a multicenter contraceptive efficacy study. World Health Organization Task Force on Methods for the Regulation of Male Fertility. Fertil Steril. 1996 Mar;65(3):626-36.

Anawalt BD, Bebb RA, Bremner WJ, Matsumoto AM. A lower dosage levonorgestrel and testosterone combination effectively suppresses spermatogenesis and circulating gonadotropin levels with fewer metabolic effects than higher dosage combinations. J Androl. 1999 May-Jun;20(3):407-14.

Zirkin BR, Santulli R, Awoniyi CA, Ewing LL. Maintenance of advanced spermatogenic cells in the adult rat testis: quantitative relationship to testosterone concentration within the testis. Endocrinology. 1989 Jun;124(6):3043-9.

Coviello AD, Matsumoto AM, Bremner WJ, Herbst KL, Amory JK, Anawalt BD, Sutton PR, Wright WW, Brown TR, Yan X, Zirkin BR, Jarow JP. Low-dose human chorionic gonadotropin maintains intratesticular testosterone in normal men with testosterone-induced gonadotropin suppression. J Clin Endocrinol Metab. 2005 May;90(5):2595-602. Epub 2005 Feb 15.

Coviello AD, Bremner WJ, Matsumoto AM, Herbst KL, Amory JK, Anawalt BD, Yan X, Brown TR, Wright WW, Zirkin BR, Jarow JP. Intratesticular testosterone concentrations comparable with serum levels are not sufficient to maintain normal sperm production in men receiving a hormonal contraceptive regimen. J Androl. 2004 Nov-Dec;25(6):931-8.

Awoniyi CA, Sprando RL, Santulli R, Chandrashekar V, Ewing LL, Zirkin BR. Restoration of spermatogenesis by exogenously administered testosterone in rats made azoospermic by hypophysectomy or withdrawal of luteinizing hormone alone. Endocrinology. 1990 Jul;127(1):177-84.

Chen H, Chandrashekar V, Zirkin BR. Can spermatogenesis be maintained quantitatively in intact adult rats with exogenously administered dihydrotestosterone? J Androl. 1994 Mar-Apr;15(2):132-8.

Meriggiola MC, Costantino A, Bremner WJ, Morselli-Labate AM. Higher testosterone dose impairs sperm suppression induced by a combined androgen-progestin regimen. J Androl. 2002 Sep-Oct;23(5):684-90.

Responsible Party:	University of Washington ( William J Bremner, MD, PhD )
Study ID Numbers:	27158-D, RFA-HD-04-030
Study First Received:	February 6, 2009
Last Updated:	October 26, 2009
ClinicalTrials.gov Identifier:	NCT00839319 History of Changes
Health Authority:	United States: Food and Drug Administration; United States: Institutional Review Board

Keywords provided by University of Washington:

hCG
testosterone
Acyline
Intratesticular hormone

Additional relevant MeSH terms:

Antineoplastic Agents, Hormonal
Antineoplastic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Reproductive Control Agents
Methyltestosterone
Chorionic Gonadotropin

Hormones
Pharmacologic Actions
Testosterone 17 beta-cypionate
Testosterone
Anabolic Agents
Therapeutic Uses
Androgens

ClinicalTrials.gov processed this record on February 08, 2010