ITT-5 Mechanisms of Spermatogenesis in Man

NCT ID: NCT02147964

Last Updated: 2019-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE2

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-30

Study Completion Date

2026-12-31

Brief Summary

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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

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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.

Conditions

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Gonadotropin Deficiency

Keywords

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intratesticular androgens testosterone dutasteride gonadotropin suppression male contraception spermatogenesis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Acyline; T Gel; placebo dutasteride, placebo ketoconazole

All men will receive Acyline 300 ug/kg subcutaneous (SQ) injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned.

Group 1: placebo oral ketoconazole + placebo oral dutasteride for 4 months

Group Type EXPERIMENTAL

Testosterone 1% Gel

Intervention Type DRUG

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Acyline

Intervention Type DRUG

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

placebo dutasteride

Intervention Type DRUG

placebo oral dutasteride PO daily for 4 months

placebo ketoconazole

Intervention Type DRUG

placebo ketoconazole daily for 4 months

Acyline; T gel; Ketoconazole; placebo

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned.

Group 2: oral ketoconazole 400 mg + placebo oral dutasteride for 4 months

Group Type EXPERIMENTAL

Testosterone 1% Gel

Intervention Type DRUG

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Acyline

Intervention Type DRUG

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

Ketoconazole

Intervention Type DRUG

ketoconazole 400 mg PO daily for 4 months

placebo dutasteride

Intervention Type DRUG

placebo oral dutasteride PO daily for 4 months

Acyline; Tgel; Ketoconazole; Dutasteride

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned.

Group 3: Ketoconazole 400mg orally daily + Dutasteride 2.5 mg orally on day 1, followed by 0.5mg daily for 4 months

Group Type EXPERIMENTAL

Testosterone 1% Gel

Intervention Type DRUG

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Acyline

Intervention Type DRUG

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

Dutasteride

Intervention Type DRUG

Dutasteride 2.5 mg (day 1) followed by 0.5 mg daily for 4 months

Ketoconazole

Intervention Type DRUG

ketoconazole 400 mg PO daily for 4 months

Acyline; Tgel; HCG

All men will receive Acyline 300 ug/kg SQ injections every 2-weeks + Testosterone 1% Gel 5g daily and then randomly assigned.

Group 4: Human Chorionic gonadotropin (HCG) 60 IU injection every other day for 4 months.

Group Type EXPERIMENTAL

Testosterone 1% Gel

Intervention Type DRUG

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Acyline

Intervention Type DRUG

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

HCG

Intervention Type DRUG

HCG 60 IU injection Subcutaneously, every other day for 4 months

Interventions

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Testosterone 1% Gel

Testosterone 1% gel 5g daily for 4 months \[all subjects\]

Intervention Type DRUG

Acyline

Acyline 300 ug/kg SQ injections every 2-weeks for 4 months \[all subjects\]

Intervention Type DRUG

Dutasteride

Dutasteride 2.5 mg (day 1) followed by 0.5 mg daily for 4 months

Intervention Type DRUG

Ketoconazole

ketoconazole 400 mg PO daily for 4 months

Intervention Type DRUG

HCG

HCG 60 IU injection Subcutaneously, every other day for 4 months

Intervention Type DRUG

placebo dutasteride

placebo oral dutasteride PO daily for 4 months

Intervention Type DRUG

placebo ketoconazole

placebo ketoconazole daily for 4 months

Intervention Type DRUG

Other Intervention Names

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T gel Testosterone gel AndroGel Avodart Human chorionic gonadotropin (HCG)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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University of Washington

OTHER

Sponsor Role lead

Responsible Party

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William Bremner

Professor of Medicine

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mara Roth, MD

Role: PRINCIPAL_INVESTIGATOR

University of Washington

William J Bremner, MD, PhD

Role: STUDY_DIRECTOR

University of Washington

Locations

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University of Washington Medical Center (Health Sciences)

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)

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.

Reference Type BACKGROUND
PMID: 19779211 (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 BACKGROUND
PMID: 20484472 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 2966691 (View on PubMed)

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. doi: 10.1530/acta.0.1200677.

Reference Type BACKGROUND
PMID: 2499150 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6093722 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6151171 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23348398 (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)

Other Identifiers

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STUDY00001449

Identifier Type: -

Identifier Source: org_study_id