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

NCT ID: NCT00839319

Last Updated: 2016-01-11

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

59 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-03-31

Study Completion Date

2010-11-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Healthy Males

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Acyline plus Placebo

Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus subcutaneous placebo hCG injection (inj) every other day (5 doses) for 10 days

Group Type EXPERIMENTAL

Acyline

Intervention Type DRUG

300 ug/kg subcutaneous injections on Day 1.

placebo hCG (no active ingredient)

Intervention Type OTHER

placebo hCG

Acyline plus 15 IU hCG

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

Group Type EXPERIMENTAL

Acyline

Intervention Type DRUG

300 ug/kg subcutaneous injections on Day 1.

hCG (human chorionic gonadotropin)

Intervention Type DRUG

15 IU subcutaneous injection every other day for 10 days (5 doses)

Acyline plus 60 IU hCG

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

Group Type EXPERIMENTAL

Acyline

Intervention Type DRUG

300 ug/kg subcutaneous injections on Day 1.

hCG (human chorionic gonadotropin)

Intervention Type DRUG

60 IU subcutaneous injection

Acyline plus 125 IU hCG

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

Group Type EXPERIMENTAL

Acyline

Intervention Type DRUG

300 ug/kg subcutaneous injections on Day 1.

hCG (human chorionic gonadotropin)

Intervention Type DRUG

125 IU subcutaneous injection

Acyline plus Testosterone gel

Acyline 300 ug/kg subcutaneous (SQ) injections on Day 1 plus Testosterone gel 75 mg/day daily for 10 days

Group Type EXPERIMENTAL

Acyline

Intervention Type DRUG

300 ug/kg subcutaneous injections on Day 1.

Testosterone gel

Intervention Type DRUG

75 mg testosterone gel applied transdermally for 10 days

Interventions

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Acyline

300 ug/kg subcutaneous injections on Day 1.

Intervention Type DRUG

placebo hCG (no active ingredient)

placebo hCG

Intervention Type OTHER

hCG (human chorionic gonadotropin)

15 IU subcutaneous injection every other day for 10 days (5 doses)

Intervention Type DRUG

hCG (human chorionic gonadotropin)

60 IU subcutaneous injection

Intervention Type DRUG

hCG (human chorionic gonadotropin)

125 IU subcutaneous injection

Intervention Type DRUG

Testosterone gel

75 mg testosterone gel applied transdermally for 10 days

Intervention Type DRUG

Other Intervention Names

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Acyline GhRH antagonist placebo drug Pregnyl Pregnyl Pregnyl Testim

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

50 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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John Amory

Professor, Department of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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William Bremner, MD, PhD

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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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.

Reference Type BACKGROUND
PMID: 1977002 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8774299 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10386821 (View on PubMed)

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. doi: 10.1210/endo-124-6-3043.

Reference Type BACKGROUND
PMID: 2498065 (View on PubMed)

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. doi: 10.1210/jc.2004-0802. Epub 2005 Feb 15.

Reference Type BACKGROUND
PMID: 15713727 (View on PubMed)

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. doi: 10.1002/j.1939-4640.2004.tb03164.x.

Reference Type BACKGROUND
PMID: 15477366 (View on PubMed)

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. doi: 10.1210/endo-127-1-177.

Reference Type BACKGROUND
PMID: 2113863 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8056636 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12185103 (View on PubMed)

Roth MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Snyder CN, Marck BT, Bremner WJ, Amory JK. Dose-dependent increase in intratesticular testosterone by very low-dose human chorionic gonadotropin in normal men with experimental gonadotropin deficiency. J Clin Endocrinol Metab. 2010 Aug;95(8):3806-13. doi: 10.1210/jc.2010-0360. Epub 2010 May 19.

Reference Type RESULT
PMID: 20484472 (View on PubMed)

Roth MY, Lin K, Bay K, Amory JK, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Page ST. Serum insulin-like factor 3 is highly correlated with intratesticular testosterone in normal men with acute, experimental gonadotropin deficiency stimulated with low-dose human chorionic gonadotropin: a randomized, controlled trial. Fertil Steril. 2013 Jan;99(1):132-139. doi: 10.1016/j.fertnstert.2012.09.009. Epub 2012 Oct 3.

Reference Type RESULT
PMID: 23040523 (View on PubMed)

Other Identifiers

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U54HD012629

Identifier Type: NIH

Identifier Source: secondary_id

View Link

27158-D

Identifier Type: -

Identifier Source: org_study_id

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