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ITT-5 Mechanisms of Spermatogenesis in Man (ITT-5)

Primary Purpose

Gonadotropin Deficiency

Status

Withdrawn

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Testosterone 1% Gel

Acyline

Dutasteride

Ketoconazole

HCG

placebo dutasteride

placebo ketoconazole

About this trial

This is an interventional treatment trial for Gonadotropin Deficiency focused on measuring intratesticular androgens, testosterone, dutasteride, gonadotropin suppression, male contraception, spermatogenesis

Eligibility Criteria

18 Years - 55 Years (Adult)MaleAccepts Healthy Volunteers

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

Sites / Locations

University of Washington Medical Center (Health Sciences)

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Arm Label

Acyline; T Gel; placebo dutasteride, placebo ketoconazole

Acyline; T gel; Ketoconazole; placebo

Acyline; Tgel; Ketoconazole; Dutasteride

Acyline; Tgel; HCG

Arm Description

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

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

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

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.

Outcomes

Primary Outcome Measures

Sperm concentration

Difference in sperm concentration at week 16 between 4 treatment groups

Secondary Outcome Measures

IT steroid concentration

It steroid concentration at week 16 between the 4 treatment groups

Full Information

NCT ID

NCT02147964

First Posted

May 21, 2014

Last Updated

December 16, 2019

Sponsor

University of Washington

1. Study Identification

Unique Protocol Identification Number

NCT02147964

Brief Title

ITT-5 Mechanisms of Spermatogenesis in Man

Acronym

ITT-5

Official Title

Mechanisms of Hormonal Control of Spermatogenesis in Man

Study Type

Interventional

2. Study Status

Record Verification Date

December 2019

Overall Recruitment Status

Withdrawn

Why Stopped

No funding was obtained for this study.

Study Start Date

June 2019 (Anticipated)

Primary Completion Date

December 2021 (Anticipated)

Study Completion Date

December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Washington

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gonadotropin Deficiency

Keywords

intratesticular androgens, testosterone, dutasteride, gonadotropin suppression, male contraception, spermatogenesis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Acyline; T Gel; placebo dutasteride, placebo ketoconazole

Arm Type

Experimental

Arm Description

Arm Title

Acyline; T gel; Ketoconazole; placebo

Arm Type

Experimental

Arm Description

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

Arm Title

Acyline; Tgel; Ketoconazole; Dutasteride

Arm Type

Experimental

Arm Description

Arm Title

Acyline; Tgel; HCG

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Testosterone 1% Gel

Other Intervention Name(s)

T gel, Testosterone gel, AndroGel

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Acyline

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Dutasteride

Other Intervention Name(s)

Avodart

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Ketoconazole

Intervention Description

ketoconazole 400 mg PO daily for 4 months

Intervention Type

Drug

Intervention Name(s)

HCG

Other Intervention Name(s)

Human chorionic gonadotropin (HCG)

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

placebo dutasteride

Intervention Description

placebo oral dutasteride PO daily for 4 months

Intervention Type

Drug

Intervention Name(s)

placebo ketoconazole

Intervention Description

placebo ketoconazole daily for 4 months

Primary Outcome Measure Information:

Title

Sperm concentration

Description

Difference in sperm concentration at week 16 between 4 treatment groups

Time Frame

16 weeks

Secondary Outcome Measure Information:

Title

IT steroid concentration

Description

It steroid concentration at week 16 between the 4 treatment groups

Time Frame

16 weeks

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mara Roth, MD

Organizational Affiliation

University of Washington

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

William J Bremner, MD, PhD

Organizational Affiliation

University of Washington

Official's Role

Study Director

Facility Information:

Facility Name

University of Washington Medical Center (Health Sciences)

City

Seattle

State/Province

Washington

ZIP/Postal Code

98195

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Undecided

Citations:

PubMed Identifier

1977002

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.

Results Reference

background

PubMed Identifier

8774299

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.

Results Reference

background

PubMed Identifier

10386821

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.

Results Reference

background

PubMed Identifier

2498065

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.

Results Reference

background

PubMed Identifier

19779211

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.

Results Reference

background

PubMed Identifier

20484472

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.

Results Reference

background

PubMed Identifier

2966691

Citation

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

Results Reference

background

PubMed Identifier

2499150

Citation

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.

Results Reference

background

PubMed Identifier

6093722

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.

Results Reference

background

PubMed Identifier

6151171

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.

Results Reference

background

PubMed Identifier

23348398

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.

Results Reference

background

PubMed Identifier

15713727

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.

Results Reference

background

Links:

URL

http://depts.washington.edu/popctr/

Description

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

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ITT-5 Mechanisms of Spermatogenesis in Man

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