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CEP-1 Hormonal Regulation of Circulating Endothelial Progenitor Cells and HDL-C in Men

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Stephanie T. Page, University of Washington
ClinicalTrials.gov Identifier:
NCT00729859
First received: August 5, 2008
Last updated: September 12, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Acyline
Drug: Acyline + Testosterone gel
Drug: Acyline + testosterone gel + anastrozole
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by University of Washington:

Primary Outcome Measures:
  • Endothelial Progenitor Cells [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
    Number of CD33 + CD134+ cells as a percentage of all lymphocytes


Secondary Outcome Measures:
  • Follicle Stimulating Hormone (FSH) [ Time Frame: Baseline, 28 days ] [ Designated as safety issue: No ]
  • Luteinizing Hormone Concentration (LH) [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Testosterone Concentration [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Estradiol Concentration [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Sex Hormone Binding Globulin (SHBG) [ Time Frame: Baseline, Day 28 ] [ Designated as safety issue: No ]
  • Quantitative Insulin Sensitivity Check Index (QUICKI) [ Time Frame: Baseline, Day 28, Day 56 ] [ Designated as safety issue: No ]
    QUICKI is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher QUICKI are associated with decreased insulin resistance and increased insulin sensitivity.

  • Homeostasis Model of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline, Day 28, Day 56 ] [ Designated as safety issue: No ]
    HOMA IR is a measure of insulin sensitivity calculated using fasting insulin and glucose concentration in a participants blood. Higher HOMA IR numbers are associated with increased insulin resistance and decreased insulin sensitivity.

  • Fasting Serum Insulin [ Time Frame: Baseline, Day 28, Day 56 ] [ Designated as safety issue: No ]
  • Fasting Lipid Levels [ Time Frame: Baseline, Day 28, Day 56 ] [ Designated as safety issue: Yes ]

Enrollment: 31
Study Start Date: December 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1
Acyline 300 µg/kg injections every two weeks (2 doses) + placebo (no active ingredients) gel daily for 28 days + oral placebo pill daily for 28 days
Drug: Acyline
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
Other Names:
  • Acyline
  • placebo testosterone gel
  • placebo pill
Experimental: Group 2
Acyline 300 µg/kg injections every two weeks (2 doses) + Testosterone gel 100 mg daily for 28 days + oral placebo pill daily for 28 days
Drug: Acyline + Testosterone gel
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
Other Names:
  • Acyline
  • testosterone gel
Experimental: Group 3
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
Drug: Acyline + testosterone gel + anastrozole
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 Names:
  • Acyline
  • Testosterone gel
  • Anastrozole

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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00729859

Sponsors and Collaborators
University of Washington
Investigators
Principal Investigator: Stephanie Page, MD, PhD University of Washington
  More Information

Additional Information:
Publications:

Responsible Party: Stephanie T. Page, Associate Professor, University of Washington
ClinicalTrials.gov Identifier: NCT00729859     History of Changes
Other Study ID Numbers: 33853-A, U54HD042454
Study First Received: August 5, 2008
Results First Received: June 2, 2011
Last Updated: September 12, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by University of Washington:
HDL
Insulin sensitivity
testosterone
estradiol
cholesterol

Additional relevant MeSH terms:
Anastrozole
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents
Androgens
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Aromatase Inhibitors
Enzyme Inhibitors
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014