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

NCT00839319 | Completed Phase 1 Results

• 2 other identifiers: 27158-DU54HD012629
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Males

Keywords

hCG; testosterone; Acyline; Intratesticular hormone

Outcome Measures

Primary Outcomes (4)

• Serum Testosterone (T)

  10 days

• Serum Luteinizing Hormone (LH)

  10 days

• Serum Follicle Stimulating Hormone (FSH)

  10 days

• Intratesticular Testosterone (ITT-T)

  10 days

Study Arms (5)

Acyline plus Placebo

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; Other: placebo hCG (no active ingredient)

Acyline plus 15 IU hCG

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; Drug: hCG (human chorionic gonadotropin)

Acyline plus 60 IU hCG

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; Drug: hCG (human chorionic gonadotropin)

Acyline plus 125 IU hCG

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; Drug: hCG (human chorionic gonadotropin)

Acyline plus Testosterone gel

EXPERIMENTAL

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

Drug: Acyline; Drug: Testosterone gel

Interventions

Acyline DRUG

300 ug/kg subcutaneous injections on Day 1.

Also known as: Acyline GhRH antagonist

Acyline plus 125 IU hCG; Acyline plus 15 IU hCG; Acyline plus 60 IU hCG; Acyline plus Placebo; Acyline plus Testosterone gel

placebo hCG (no active ingredient) OTHER

placebo hCG

Also known as: placebo drug

Acyline plus Placebo

hCG (human chorionic gonadotropin) DRUG

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

Also known as: Pregnyl

Acyline plus 15 IU hCG

Testosterone gel DRUG

75 mg testosterone gel applied transdermally for 10 days

Also known as: Testim

Acyline plus Testosterone gel

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (1)

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (11)

• 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.

  PMID: 1977002 BACKGROUND

• 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.

  PMID: 8774299 BACKGROUND

• 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.

  PMID: 10386821 BACKGROUND

• 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.

  PMID: 2498065 BACKGROUND

• 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.

  PMID: 15713727 BACKGROUND

• 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.

  PMID: 15477366 BACKGROUND

• 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.

  PMID: 2113863 BACKGROUND

• 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.

  PMID: 8056636 BACKGROUND

• 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.

  PMID: 12185103 BACKGROUND

• 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.

  PMID: 20484472 RESULT

• 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.

  PMID: 23040523 RESULT

MeSH Terms

Interventions

acyline; Chorionic Gonadotropin; Testosterone

Intervention Hierarchy (Ancestors)

Gonadotropins; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Placental Hormones; Peptides; Amino Acids, Peptides, and Proteins; Pregnancy Proteins; Proteins; Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones

Results Point of Contact

• Title: Mara Roth, MD
• Organization: University of Washington

mylang@u.washington.edu

206-221-0519

Study Officials

• William Bremner, MD, PhD

  University of Washington

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Department of Medicine

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 9, 2009
• Study Start: March 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: November 1, 2010
• Last Updated: January 11, 2016
• Results First Posted: November 16, 2010

Record last verified: 2015-12

Locations

US (1)