CEP-1 Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men
Condition: Healthy
Study type: Interventional
Phase: Phase 2

Summary: 
      The original purpose of this research study was to understand the effects of testosterone (T)
      and estrogen on stem cells in the blood. The knowledge would be used to help understand the
      effects of T and estrogen on cardiovascular (heart and blood vessel) disease, and to help in
      the development of a safe male hormonal contraceptive.

      The effect of androgens on the number of circulating endothelial progenitor (CEP) cells would
      best be observed in group 1 (placebo). Upon observation of group 1 under original protocol,
      changes in CEP cells were not significant but there were changes in markers of inflammation,
      lipids, and HDL protein composition. A modification to the protocol and title were made to
      reflect this for groups 2 and 3: Hormonal regulation of HDL-C in Men.
    

Detailed description: 
      We will be administering three drugs: testosterone gel (T), anastrozole, and acyline. We want
      to see their effects on stem cells and hormone levels in the blood. Acyline suppress
      luteinizing hormone(LH) and follicle-stimulating hormone(FSH), which are hormones made by the
      pituitary gland, thus blocking the signal from the brain that causes the testes to make
      testosterone. Therefore acyline blocks testosterone production. Some men may experience side
      effects such as hot flashes or irritability from the low levels of T caused by acyline. We
      are studying whether adding T to acyline will reduce or eliminate these side effects.

      Since heart disease is a common problem in men we want to know about the effects of male
      hormonal contraception on the cardiovascular system. One way to evaluate these risks is to
      measure the number of progenitor cells and the types of cholesterol in the blood. Progenitor
      cells are cells that travel in the blood and go to areas of blood vessel injury to help
      repair the damage amd may help prevent heart attacks and stokes. Some studies suggest that T
      administration may increase the number of these cells in the blood but other studies have
      shown that estrogen may be responsible for this effect. In addition, T and estrogen may
      affect the amount and type of HDL cholesterol in the blood. This is the "good" cholesterol
      that is thought to protect people from heart attacks and strokes. Therefore, more studies to
      test the effects of T and estrogen on progenitor cells in the blood and to understand HDL
      cholesterol in men receiving testosterone are needed.

      Acyline is an experimental drug. The FDA allows its use only in research with a small number
      of volunteers. So far, over 125 men have received acyline. Anastrozole is a drug that blocks
      the production of estrogen from testosterone. Anastrozole has been given to men safely in the
      past. Anastrozole is not approved for use in men and is also an experimental drug.
      Testosterone gel will also be used in this study. It is FDA approved for use in men with low
      testosterone levels.
    

Intervention name(s): Acyline; Acyline + Testosterone gel; Acyline + testosterone gel + anastrozole
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + placebo Testosterone gel daily for 28 days + placebo oral anastrozole pill daily for 28 days; Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + Testosterone gel 100 mg daily for 28 days + placebo oral pill 1 mg daily for 28 days; Acyline 300 μg/kg injections every two weeks (2 doses) for 28 days + Testosterone gel 100 mg daily for 28 days + oral anastrozole pill 1 mg daily for 28 days
Other intervention name(s): placebo testosterone gel; placebo pill; Acyline; testosterone gel; Acyline; Testosterone gel; Anastrozole
Intervention MeSH terms: Methyltestosterone; Anastrozole; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate; Acyline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Prevention
Keywords: HDL; Insulin sensitivity; testosterone; estradiol; cholesterol