Clinical trial NCT00729859: CEP-1 Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men
Official title: Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men Title Changed With New Protocol (12/14/09): Hormonal Regulation of HDL-C in Men
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Healthy
Keywords: HDL
Insulin sensitivity
testosterone
estradiol
cholesterol
Lead sponsor: University of Washington
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2008-08-08
Enrollment: 31
Sex: MALE
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Males age 18-55 years
* Normal serum total testosterone (300 ng/dl-1000 ng/dl)
* Normal LH and FSH levels
* Taking no regular medications
* Normal baseline serum hematology, chemistry and liver function tests
* Agrees not to donate blood during the study
* Agrees to use a form of contraception during the study
* Subject must be able to comply with all study procedures

Exclusion Criteria:

* Clinically significant screening assessments or other relevant disease, allergy or surgery, as revealed by history, physical examination and/or laboratory assessments, which may limit participation or prevent completion of the study
* History of prostate cancer, breast cancer, or benign prostatic hypertrophy
* Prostate-specific antigen (PSA) \> 3.0
* History of regular, chronic testosterone or anabolic steroid use in the past year
* Chronic medical illness, prostate disease, or cardiovascular disease
* History of a bleeding disorder or need for anticoagulation
* Skin condition that might interfere with or be exacerbated by T gel use
* Sitting systolic blood pressure \> 180mm Hg or \<90 mm Hg or sitting diastolic blood pressure \>110 mm Hg or \< 60 mm Hg.
* History of clinically significant, untreated sleep apnea
* Participation in another drug-related research study within the past 2 months
* Participating in a regular physical relationship with a pregnant woman
* History of hypersensitivity to any of the study medications (T gel, anastrozole, acyline)
* History of medical or surgical therapy for benign prostatic hypertrophy
* Hematocrit \> 55%
* History of drug or alcohol abuse within last 6 months
* Abnormal digital rectal exam at screening

Primary outcomes:
measure: Endothelial Progenitor Cells
timeFrame: Baseline, Day 28
Secondary outcomes:
measure: Follicle Stimulating Hormone (FSH)
timeFrame: Baseline, 28 days
measure: Luteinizing Hormone Concentration (LH)
timeFrame: Baseline, Day 28
measure: Testosterone Concentration
timeFrame: Baseline, Day 28
measure: Estradiol Concentration
timeFrame: Baseline, Day 28
measure: Sex Hormone Binding Globulin (SHBG)
timeFrame: Baseline, Day 28
measure: Quantitative Insulin Sensitivity Check Index (QUICKI)
timeFrame: Baseline, Day 28, Day 56
measure: Homeostasis Model of Insulin Resistance (HOMA-IR)
timeFrame: Baseline, Day 28, Day 56
measure: Fasting Serum Insulin
timeFrame: Baseline, Day 28, Day 56
measure: Fasting Lipid Levels
timeFrame: Baseline, Day 28, Day 56
Other outcomes:
Locations:
Study officials:
affiliation: University of Washington
name: Stephanie Page, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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