ITT-5 Mechanisms of Spermatogenesis

Condition(s) targeted: Gonadotropin Deficiency

Intervention: Testosterone 1% Gel (Drug); Acyline (Drug); Dutasteride (Drug); Ketoconazole (Drug); HCG (Drug); placebo dutasteride (Drug); placebo ketoconazole (Drug)

Phase: Phase 2

Status: Not yet recruiting

Sponsored by: University of Washington

Official(s) and/or principal investigator(s):
Mara Roth, MD, Principal Investigator, Affiliation: University of Washington
William J Bremner, MD, PhD, Study Director, Affiliation: University of Washington

Overall contact:
Iris Nielsen, Phone: 206-221-5473, Email: inielsen@uw.edu

The purpose of this investigational drug study is to determine how much male hormone, testosterone, is needed to maintain sperm production in the testis.

Official title: Mechanisms of Hormonal Control of Spermatogenesis in Man

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Sperm concentration

Secondary outcome: IT steroid concentration

Detailed description: This is a nine-month research study examining the effects on androgen treatment on sperm production in healthy men. There are three phase to the study, a 2-month screening phase, 4-month treatment and 3-month follow-up. In this study, the investigators aim to define a quantitative relationship between intra-testicular testosterone (IT-T) and spermatogenesis in man. Hormone levels will be measured in a small amount of testicular fluid at the beginning and end of treatment and sperm concentration will be measured.

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Male.

Criteria:

Inclusion Criteria:

- Males age 18-55

- In general good health based on normal screening evaluation

- Normal serum testosterone, lutenizing hormone (LH) and follicle stimulating hormone

(FSH)

- Prostate Specific Antigen (PSA) < 3. 0

- Agrees not to donate blood or participate in another research study during the study

- Informed consent

- Must be willing to use a reliable form of contraception during the study

Exclusion Criteria:

- Participation in a long-term male contraceptive study within the past three months

- History of testosterone or anabolic steroid abuse in the past

- History of or current skin disorder that will interfere with testosterone gel

- Poor general health or significantly abnormal screening blood results

- History of or current testicular or prostate disease

- History of a bleeding disorder or need for anticoagulation

- History of untreated sleep apnea and/or major psychiatric problems

- BMI > 32

- History of or current liver disease

- Chronic pain syndrome

- Current use of terfenidine, astemizole, cisapride, budesonide, felodipine,

fluticasone, lovastatin, midazolam, sildenafil, or vardenafil

- Use of glucocorticoids or underlying adrenal insufficiency

- Active drug or alcohol abuse within the past year

Iris Nielsen, Phone: 206-221-5473, Email: inielsen@uw.edu

University of Washington Medical Center (Health Sciences), Seattle, Washington 98195, United States; Not yet recruiting
Iris Nielsen, Phone: 206-221-5473, Email: nielseni@uw.edu
Kathy Winter, Phone: 206-616-0484, Email: klwinter@uw.edu
Mara Roth, MD, Principal Investigator
John Amory, MD, MPH, Sub-Investigator
Stephanie Page, MD, PhD, Sub-Investigator
Bradley Anawalt, MD, Sub-Investigator

Dedicated to basic and clinical research focused primarily on the male reproductive system

Related publications:

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.

Roth MY, Lin K, Amory JK, Matsumoto AM, Anawalt BD, Snyder CN, Kalhorn TF, Bremner WJ, Page ST. Serum LH correlates highly with intratesticular steroid levels in normal men. J Androl. 2010 Mar-Apr;31(2):138-45. doi: 10.2164/jandrol.109.008391. Epub 2009 Sep 24.

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.

Trachtenberg J, Zadra J. Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5.

Nashan D, Knuth UA, Weidinger G, Nieschlag E. The antimycotic drug terbinafine in contrast to ketoconazole lacks acute effects on the pituitary-testicular function of healthy men: a placebo-controlled double-blind trial. Acta Endocrinol (Copenh). 1989 May;120(5):677-81.

Pont A, Graybill JR, Craven PC, Galgiani JN, Dismukes WE, Reitz RE, Stevens DA. High-dose ketoconazole therapy and adrenal and testicular function in humans. Arch Intern Med. 1984 Nov;144(11):2150-3.

Van Tyle JH. Ketoconazole. Mechanism of action, spectrum of activity, pharmacokinetics, drug interactions, adverse reactions and therapeutic use. Pharmacotherapy. 1984 Nov-Dec;4(6):343-73. Review.

Roth MY, Nya-Ngatchou JJ, Lin K, Page ST, Anawalt BD, Matsumoto AM, Marck BT, Bremner WJ, Amory JK. Androgen synthesis in the gonadotropin-suppressed human testes can be markedly suppressed by ketoconazole. J Clin Endocrinol Metab. 2013 Mar;98(3):1198-206. doi: 10.1210/jc.2012-3527. Epub 2013 Jan 24.

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.

Starting date: January 2015
Last updated: December 1, 2014