Official Title: “Effect of Testosterone Replacement on Insulin Resistance in Hypogonadal, Non-Obese Men With Metabolic Syndrome”

This study aims to determine whether testosterone replacement improves insulin sensitivity in non-obese men with low testosterone and the metabolic syndrome. The metabolic syndrome includes three of the following five conditions, 1) an elevated blood pressure (greater than 130/85), 2) a triglyceride level greater than 150 mg/dl, 3) an HDL-cholesterol less than 40 mg/dl, 4) glucose levels greater than 100 mg/dl, and 5) a waist measurement greater than 40 inches.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: December 2008

In this proposal, we will examine the relationship between hypogonadism and insulin sensitivity. The strongest relationship between hypogonadism and insulin resistance appears to reside in men with the metabolic syndrome who have a normal BMI. The causal relationship between these two conditions is unknown. Therefore, we propose to determine if testosterone replacement in hypogonadal non-obese men with metabolic syndrome will improve insulin sensitivity. Data obtained from this preliminary investigation, will hopefully result in a hypothesis that can be tested in a larger, more rigorous trial in the future.

Intervention(s) in this Clinical Trial

• Radiation: Testosterone gel
  • testosterone gel, applied daily. Dosed to achieve testosterone level <500 ng/dL. Possible doses include 2.5g, 5g, 7.5g or 10g gel packets.
• Drug: Placebo for testosterone gel
  • Placebo gel, 2.5g for each gel packet

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Subjects in this arm will receive testosterone gel
• Placebo Comparator: 2

Primary Measures

• Change in insulin sensitivity as measured by HOMA-IR
  • Time Frame: 18 weeks
    Safety Issue?: No

Secondary Measures

• Changes in parameters of the Metabolic Syndrome
  • Time Frame: 18 weeks
    Safety Issue?: No
• Changes in body composition
  • Time Frame: 18 weeks
    Safety Issue?: No
• Changes in total and high MW adiponectin levels
  • Time Frame: 18 weeks
    Safety Issue?: No

• Inclusion Criteria: (subjects must meet both criteria)
• Metabolic syndrome (have 3 out of the following 4 criteria):
• 1. BP > 130/85 or on antihypertensive therapy
• 2. Fasting glucose > 100 mg/dl
• 3. Fasting TG > 150 mg/dl or on a triglyceride lowering agent (fenofibrate, gemfibrozil, niacin in doses of >= 500 mg/day, or fish oils in doses of >=2000mg
• DHA+EPA)
• 4. Fasting HDL-C < 40 mg/dl Note that the waist circumference will not be used as one of the criteria for the metabolic syndrome for this study because we are studying non-obese subjects.
• Total Testosterone less than 300 ng/dl

Exclusion Criteria:

• Women.
• Men less than 20 years of age.
• BMI > or = to 30 kg/M2.
• Use of testosterone preparations within 1 year of the screening visit
• Use of hypoglycemic medications within the previous 3 months.
• Fasting blood glucose > 126 mg/dl.
• The following men will be excluded because of the potential safety issues in the placebo treated group:
• 1. Creatinine greater than 1.4 mg/dl
• 2. Triglyceride levels greater than 500 mg/dl
• 3. HDL-C levels less than 20 mg/dl
• 4. Blood pressure greater than 160/90
• The following men will be excluded because of the potential side effects of testosterone therapy:
• 1. Men greater than 65 years of age
• 2. International prostate symptom score >19
• 3. PSA greater than 2.5
• 4. History of benign prostatic hypertrophy
• 5. History of prostate cancer
• 6. Abnormal digital rectal exam
• 7. Hg greater than 16 mg/dl or Hct greater than 48%
• 8. peripheral edema

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 20 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: McGuire Research Institute

Overall Clinical Trial Officials and Contacts

Sonja K Fredrickson, MD Principal Investigator Hunter Holmes McGuire VA Medical Center  

Overall Contact: Helen Stewart, RN (804)675-5000 helen.stuart@va.gov

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00487734

Study ID Number: 01274

ClinicalTrials.gov Identifier: NCT00487734

Health Authority: United States: Institutional Review Board