ITT4 Intratesticular Hormonal Milieu in Man (ITT4)
ITT4
Mechanisms of Control of the Intratesticular Hormonal Milieu in Man
2 other identifiers
interventional
46
1 country
1
Brief Summary
The purpose of this research 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. Specific Aims:
- 1.to determine if ketoconazole plus acyline will suppress intratesticular testosterone(ITT) to a greater degree than acyline alone.
- 2.to determine if dutasteride plus acyline will suppress intratesticular dihydrotestosterone (IT-DHT) to a greater degree than acyline alone.
- 3.to determine if anastrazole plus acyline will suppress intratesticular estradiol(IT-E2) to a greater degree than acyline alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Jan 2011
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 4, 2010
CompletedFirst Posted
Study publicly available on registry
October 6, 2010
CompletedStudy Start
First participant enrolled
January 1, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
March 1, 2012
CompletedResults Posted
Study results publicly available
January 29, 2014
CompletedMarch 31, 2014
February 1, 2014
1.2 years
October 4, 2010
August 20, 2013
March 3, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Intratesticular Testosterone (IT-T) Level
10 days
Intratesticular Dihydrotestosterone (DHT) Level
10 days
Intratesticular Androstenedione (ADD) Level
10 days
Study Arms (5)
Acyline & T Gel & Placebo Ketoconazole
PLACEBO COMPARATORAcyline 300 mcg/kg on Day 1 + 1% testosterone gel (T gel) 5 gm daily Days 1-10, + placebo tab PO 1x daily, Day 3-10
Acyline & T Gel & Ketoconazole 400
EXPERIMENTALAcyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Days 1-10, + ketoconazole 400mg PO 1x daily, Days 3-10
Acyline & T gel & Ketoconazole 800
EXPERIMENTALAcyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Day 1-10, + ketoconazole 800mg PO 1x daily, Days 3-10
Acyline & T gel & Dutasteride
EXPERIMENTALAcyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Day 1-10, + dutasteride 2.5 mg PO 1x daily, Days 3-10
Group 5: anastrazole
EXPERIMENTALAcyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Day 1-10, + anastrazole 1 mg PO 1x daily, Days 3-10
Interventions
300 mcg/kg on Day 1
5 gm of 1% T Gel applied transdermally for 10 days
Eligibility Criteria
You may qualify if:
- Males age 18-50
- Normal serum testosterone, LH and FSH
- prostate-specific antigen (PSA) \< 4.0
- Agrees not to donate blood or participate in another research study during the study
- Informed consent
- Able to understand and comply with protocol requirements, instructions and protocol-stated restrictions
- In general good health based on normal screening evaluation (consisting of a medical history, physical exam, normal serum chemistry and hematology)
- Must be willing to use a reliable form of contraception during the study
You may not qualify if:
- Poor general health, with clinically significant abnormal blood results
- Participation in a long-term male contraceptive study within the past three months
- Participation in long-term contraceptive or drug study within the past 3 months
- History of or current liver disease
- Current use of terfenadine, astemizole, cisapride, budesonide, felodipine, fluticasone, lovastatin, midazolam, sildenafil, or vardenafil
- History of testicular, prostate, or scrotal surgery/trauma or genital abnormal exam
- BMI \> 32
- History of sleep apnea and/or major psychiatric problems
- Chronic pain syndrome
- History of testosterone or anabolic steroid abuse currently or in the past
- Known bleeding disorder or current use of anticoagulation
- History of or current skin disorder that will interfere with testosterone gel
- Unwilling to adhere to protocol-stated restrictions while in the study
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Washington
Seattle, Washington, 98195, United States
Related Publications (14)
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: 1977002BACKGROUNDWu 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: 8774299BACKGROUNDAnawalt 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: 10386821BACKGROUNDZirkin 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: 2498065BACKGROUNDCoviello 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: 15713727BACKGROUNDRoth 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.
PMID: 19779211BACKGROUNDTrachtenberg J, Zadra J. Steroid synthesis inhibition by ketoconazole: sites of action. Clin Invest Med. 1988 Feb;11(1):1-5.
PMID: 2966691BACKGROUNDNashan 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.
PMID: 2499150BACKGROUNDPont 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.
PMID: 6093722BACKGROUNDVan 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.
PMID: 6151171BACKGROUNDSoriano-Guillen L, Lahlou N, Chauvet G, Roger M, Chaussain JL, Carel JC. Adult height after ketoconazole treatment in patients with familial male-limited precocious puberty. J Clin Endocrinol Metab. 2005 Jan;90(1):147-51. doi: 10.1210/jc.2004-1438. Epub 2004 Nov 2.
PMID: 15522928BACKGROUNDHarris KA, Weinberg V, Bok RA, Kakefuda M, Small EJ. Low dose ketoconazole with replacement doses of hydrocortisone in patients with progressive androgen independent prostate cancer. J Urol. 2002 Aug;168(2):542-5.
PMID: 12131305BACKGROUNDHerbst KL, Coviello AD, Page S, Amory JK, Anawalt BD, Bremner WJ. A single dose of the potent gonadotropin-releasing hormone antagonist acyline suppresses gonadotropins and testosterone for 2 weeks in healthy young men. J Clin Endocrinol Metab. 2004 Dec;89(12):5959-65. doi: 10.1210/jc.2003-032123.
PMID: 15579744BACKGROUNDRoth 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.
PMID: 23348398RESULT
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Mara Roth, MD
- Organization
- University of Washington
Study Officials
- PRINCIPAL INVESTIGATOR
Mara Y Roth, MD
University of Washington
Publication Agreements
- PI is Sponsor Employee
- Yes
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- SINGLE
- Who Masked
- PARTICIPANT
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
October 4, 2010
First Posted
October 6, 2010
Study Start
January 1, 2011
Primary Completion
March 1, 2012
Study Completion
March 1, 2012
Last Updated
March 31, 2014
Results First Posted
January 29, 2014
Record last verified: 2014-02