Clinical trial NCT02147964: ITT-5 Mechanisms of Spermatogenesis in Man
Official title: Mechanisms of Hormonal Control of Spermatogenesis in Man
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Gonadotropin Deficiency
Keywords: intratesticular androgens
testosterone
dutasteride
gonadotropin suppression
male contraception
spermatogenesis
Lead sponsor: University of Washington
Sponsor class: OTHER
First posted: 2014-05-28
Enrollment: 0
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility 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

Primary outcomes:
measure: Sperm concentration
timeFrame: 16 weeks
Secondary outcomes:
measure: IT steroid concentration
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Seattle
country: United States
facility: University of Washington Medical Center (Health Sciences)
state: Washington
Study officials:
affiliation: University of Washington
name: Mara Roth, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Washington
name: William J Bremner, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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. doi: 10.1002/j.1875-9114.1984.tb03398.x.
citation: 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.
citation: 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.