ITT4 Intratesticular Hormonal Milieu in Man (ITT4) (ITT4)

March 3, 2014 updated by: Mara Roth, University of Washington

Mechanisms of Control of the Intratesticular Hormonal Milieu in Man

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Five drugs will be used in this study: acyline, testosterone gel, ketoconazole, dutasteride, and anastrazole.

Acyline suppresses luteinizing hormone (LH) and follicle stimulating hormone (FSH), which are hormones made by the pituitary gland in the brain, thus blocking the signal from the brain that causes the testes to make testosterone. Therefore, acyline blocks testosterone production. Men may experience some side effects from the low levels of testosterone caused by acyline. Acyline is an experimental drug. Over 125 men have received acyline from our lab. Acyline will be given by injection, and injections are formulated by subject's weight and may be given in multiple injections.

Testosterone gel is given to replace testosterone level back to the normal range. Testosterone gel is approved for use in men with low testosterone levels.

Ketoconazole suppresses testosterone production as well. Ketoconazole works in the adrenal glands to prevent testosterone production. It is approved by the U.S. FDA for treatment of fungal infections but for this study the use is considered investigational.

Dutasteride blocks metabolism of testosterone into dihydrotestosterone (DHT). It is approved by the FDA for treatment of benign enlargement of the prostate gland, but the use is considered investigational in this study. Also, the dose is 5 times higher than the FDA approved dose.

Anastrazole blocks metabolism of testosterone into estradiol. It is approved by the FDA for treatment of breast cancer but its use is considered investigational in this study.

Participation will last approximately 2 months. The study involves a minimum of 7 visits. Clinic visits at Screening, Day 3 and Day 10 will take about 1-1.5 hours each. On Day 3 & 10 a fine needle aspiration of one testis will be performed. The Day 1 visit will take approximately 45 minutes. The Day 7 visit will take about 15 minutes. The Day 17 and Day 40 visits will take approximately 30 minutes each. Over the course of the study, which includes 7 separate blood draws, approximately 12 ounces (one and a half cups) of blood will be drawn. The acyline will be given by injection. The testosterone or placebo gel is applied to the skin on the chest, upper arms, and upper back. The ketoconazole, dutasteride, anastrazole, or placebo medication will be taken by mouth.

Subjects randomly assigned to Group 3 will have a Cosyntropin Stimulation Test performed at the day 10 visit to evaluate the function of adrenal glands.

This is NOT a trial of a male contraceptive, and the study medications will not prevent pregnancy. Subjects must use an acceptable form of birth control.

Study Type

Interventional

Enrollment (Actual)

46

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

INCLUSION CRITERIA:

  • 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

EXCLUSION CRITERIA:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Acyline & T Gel & Placebo Ketoconazole
Acyline 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
Drug: Acyline
300 mcg/kg on Day 1
Other Names:
  • Acyline GnRH antagonist
Drug: Testosterone gel
5 gm of 1% T Gel applied transdermally for 10 days
Other Names:
  • Androgel
Drug: Placebo ketoconazole
placebo to mimic ketoconazole
Experimental: Acyline & T Gel & Ketoconazole 400
Acyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Days 1-10, + ketoconazole 400mg PO 1x daily, Days 3-10
Drug: Acyline
300 mcg/kg on Day 1
Other Names:
  • Acyline GnRH antagonist
Drug: Testosterone gel
5 gm of 1% T Gel applied transdermally for 10 days
Other Names:
  • Androgel
Drug: ketoconazole 400
400 mg PO daily, Days 3-10
Other Names:
  • Teva
Experimental: Acyline & T gel & Ketoconazole 800
Acyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Day 1-10, + ketoconazole 800mg PO 1x daily, Days 3-10
Drug: Acyline
300 mcg/kg on Day 1
Other Names:
  • Acyline GnRH antagonist
Drug: Testosterone gel
5 gm of 1% T Gel applied transdermally for 10 days
Other Names:
  • Androgel
Drug: Ketoconazole 800
800 mg PO daily, Day 3-10
Other Names:
  • Teva
Experimental: Acyline & T gel & Dutasteride
Acyline 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
Drug: Acyline
300 mcg/kg on Day 1
Other Names:
  • Acyline GnRH antagonist
Drug: Testosterone gel
5 gm of 1% T Gel applied transdermally for 10 days
Other Names:
  • Androgel
Drug: Dutasteride
2.5 mg PO daily, Day 3-10
Other Names:
  • Avodart
Experimental: Group 5: anastrazole
Acyline 300 mcg/kg on Day 1 + 1% testosterone gel 5 gm daily Day 1-10, + anastrazole 1 mg PO 1x daily, Days 3-10
Drug: Acyline
300 mcg/kg on Day 1
Other Names:
  • Acyline GnRH antagonist
Drug: Testosterone gel
5 gm of 1% T Gel applied transdermally for 10 days
Other Names:
  • Androgel
Drug: Anastrozole
1 mg PO daily, Day 3-10
Other Names:
  • Arimidex

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Intratesticular Testosterone (IT-T) Level
Time Frame: 10 days
10 days
Intratesticular Dihydrotestosterone (DHT) Level
Time Frame: 10 days
10 days
Intratesticular Androstenedione (ADD) Level
Time Frame: 10 days
10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Washington

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

  • Principal Investigator: Mara Y Roth, MD, University of Washington

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

March 1, 2012

Study Completion (Actual)

March 1, 2012

Study Registration Dates

First Submitted

October 4, 2010

First Submitted That Met QC Criteria

October 4, 2010

First Posted (Estimate)

October 6, 2010

Study Record Updates

Last Update Posted (Estimate)

March 31, 2014

Last Update Submitted That Met QC Criteria

March 3, 2014

Last Verified

February 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38692-K
  • U54HD012629 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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