Effect of Testosterone Replacement on Insulin Resistance

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 Overview

• Status: Completed
• Conditions: Metabolic Syndrome; Hypogonadism
• Intervention / Treatment: Radiation: Testosterone gel; Drug: Placebo for testosterone gel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2	Drug: Placebo for testosterone gel; Placebo gel, 2.5g for each gel packet
Experimental: 1; Subjects in this arm will receive testosterone gel	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.; Other Names: Androgel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in insulin sensitivity as measured by HOMA-IR	18 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Changes in parameters of the Metabolic Syndrome	18 weeks
Changes in body composition	18 weeks
Changes in total and high MW adiponectin levels	18 weeks

Collaborators and Investigators

• Sponsor: McGuire Research Institute
• Collaborators: Solvay Pharmaceuticals
• Investigators: Principal Investigator: Sonja K Fredrickson, MD, Hunter Holmes McGuire VA Medical Center

Study record dates

Study Major Dates

• Study Start: August 1, 2007
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: June 15, 2007
• First Submitted That Met QC Criteria: June 18, 2007
• First Posted (Estimate): June 19, 2007

Study Record Updates

• Last Update Posted (Estimate): October 23, 2012
• Last Update Submitted That Met QC Criteria: October 22, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Insulin Resistance; Metabolic Syndrome; Hypogonadism
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Disease; Gonadal Disorders; Hyperinsulinism; Syndrome; Metabolic Syndrome; Insulin Resistance; Hypogonadism; Physiological Effects of Drugs; Antineoplastic Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Androgens; Anabolic Agents; Testosterone; Methyltestosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate
• Other Study ID Numbers: 01274