ITT4 Intratesticular Hormonal Milieu in Man (ITT4)
Condition: Healthy Males
Study type: Interventional
Phase: Phase 1/Phase 2

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.
    

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.
    

Intervention name(s): Acyline; Testosterone gel; ketoconazole 400; Ketoconazole 800; Dutasteride; Anastrozole; Placebo ketoconazole
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): 300 mcg/kg on Day 1; 5 gm of 1% T Gel applied transdermally for 10 days; 400 mg PO daily, Days 3-10; 800 mg PO daily, Day 3-10; 2.5 mg PO daily, Day 3-10; 1 mg PO daily, Day 3-10; placebo to mimic ketoconazole
Other intervention name(s): Acyline GnRH antagonist; Androgel; Teva; Teva; Avodart; Arimidex
Intervention MeSH terms: Ketoconazole; Anastrozole; Testosterone; Dutasteride; Acyline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: testosterone; acyline; ketoconazole; dutasteride; anastrazole; Intratesticular hormone concentration