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

September 12, 2012 updated by: Stephanie T. Page, University of Washington

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

31

Phase

  • Phase 2

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 55 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Male

Description

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

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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:
  • placebo pill
  • placebo testosterone gel
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:
  • testosterone gel
  • Acyline
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:
  • Anastrozole
  • Testosterone gel
  • Acyline

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Endothelial Progenitor Cells
Time Frame: Baseline, Day 28
Number of CD33 + CD134+ cells as a percentage of all lymphocytes
Baseline, Day 28

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Follicle Stimulating Hormone (FSH)
Time Frame: Baseline, 28 days
Baseline, 28 days
Luteinizing Hormone Concentration (LH)
Time Frame: Baseline, Day 28
Baseline, Day 28
Testosterone Concentration
Time Frame: Baseline, Day 28
Baseline, Day 28
Estradiol Concentration
Time Frame: Baseline, Day 28
Baseline, Day 28
Sex Hormone Binding Globulin (SHBG)
Time Frame: Baseline, Day 28
Baseline, Day 28
Quantitative Insulin Sensitivity Check Index (QUICKI)
Time Frame: Baseline, Day 28, Day 56
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.
Baseline, Day 28, Day 56
Homeostasis Model of Insulin Resistance (HOMA-IR)
Time Frame: Baseline, Day 28, Day 56
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.
Baseline, Day 28, Day 56
Fasting Serum Insulin
Time Frame: Baseline, Day 28, Day 56
Baseline, Day 28, Day 56
Fasting Lipid Levels
Time Frame: Baseline, Day 28, Day 56
Baseline, Day 28, Day 56

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: Stephanie Page, MD, PhD, 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

December 1, 2008

Primary Completion (Actual)

May 1, 2010

Study Completion (Actual)

May 1, 2010

Study Registration Dates

First Submitted

August 5, 2008

First Submitted That Met QC Criteria

August 5, 2008

First Posted (Estimate)

August 8, 2008

Study Record Updates

Last Update Posted (Estimate)

October 12, 2012

Last Update Submitted That Met QC Criteria

September 12, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 33853-A
  • U54HD042454 (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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