Testosterone Effects on Men With the Metabolic Syndrome
Primary Purpose
Metabolic Syndrome
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Testosterone
Anastrozole
Goserelin
Sponsored by
About this trial
This is an interventional treatment trial for Metabolic Syndrome focused on measuring Testosterone, Insulin resistance, Insulin sensitivity, Metabolic disorders
Eligibility Criteria
Inclusion Criteria:
- Age 50-75 yr
Diagnosis of the metabolic syndrome defined by the American Heart Association/National Heart, Lung, and Blood Institute guidelines as the presence of three or more of the following:
- Waist circumference > 102 cm
- Serum triglycerides > 150 mg/dL
- HDL cholesterol < 40 mg/dL
- Blood pressure > 130 mm Hg systolic or 85 mm Hg diastolic, or treatment with anti-hypertensives
- Fasting serum glucose > 100 mg/dL
- Plasma total testosterone level less than 300 ng/dL (1 SD below the mean for young healthy men)
- Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)
- Normal TSH, prolactin and prostate specific antigen (PSA) levels (<2.5 ng/mL)
Exclusion Criteria:
- New diagnosis of type 2 diabetes as defined by the ADA criteria: fasting glucose greater than 126 mg/dL or random blood glucose greater than 200 mg/dL on two occasions, or on oral hypoglycemic agents
- History of testicular disorders (i.e. cryptorchidism)
- History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
- History of prostate cancer
- History of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence)
- Symptoms of urinary outflow obstruction (i.e. benign prostatic hypertrophy)
- Illicit drug use or heavy alcohol use (>4 drinks/day)
- Allergic disorders
- Current medications (must exclude individuals taking the following medications: Testosterone, Cimetidine, Spironolactone, Ketoconazole, Finasteride, DHEA, Androstenedione, Oral steroids, GnRH analogs)
Sites / Locations
Outcomes
Primary Outcome Measures
insulin sensitivity
muscle and body fat distribution
VO2 max
resting metabolic rate
muscle biopsy analysis
Secondary Outcome Measures
Full Information
NCT ID
NCT00382057
First Posted
September 26, 2006
Last Updated
December 4, 2008
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
1. Study Identification
Unique Protocol Identification Number
NCT00382057
Brief Title
Testosterone Effects on Men With the Metabolic Syndrome
Official Title
Effect of Increasing Testosterone Levels on Insulin Sensitivity in Men With the Metabolic Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
November 2008
Overall Recruitment Status
Withdrawn
Study Start Date
May 2006 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
March 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
4. Oversight
5. Study Description
Brief Summary
The metabolic syndrome is a medical condition defined by high levels of cholesterol in the blood, high blood pressure, central obesity (gain in fat around the region of the stomach), and insulin resistance (body responds less well to insulin). This state of impaired insulin resistance can lead to type 2 diabetes mellitus, which is one of the most common metabolic disorders in the U.S. Numerous studies have shown an inverse relationship between insulin resistance and testosterone levels in men, however, causality has not been established. This protocol investigates the role of testosterone in modulating insulin sensitivity in insulin resistant states such as the metabolic syndrome. The hypothesis is that testosterone administration will improve insulin sensitivity.
Detailed Description
This protocol will address the impact of three months of testosterone (T) therapy on all components of the metabolic syndrome and the mechanism underlying changes in insulin sensitivity by analyzing changes in body composition, and detailed studies of fat metabolism and skeletal muscle. In addition, this protocol will address the role of estradiol (E2) in mediating the effect of testosterone on insulin sensitivity.
Seventy-two subjects will undergo a screening visit to assess eligibility after which a baseline evaluation will be performed. The baseline metabolic assessment will consist of an intravenous glucose tolerance test (IVGTT) to measure insulin sensitivity, MRI and DEXA scan to assess muscle and body fat distribution, VO2 max test and resting metabolic rate, and a muscle biopsy to look at how the muscle is affected by insulin and testosterone.
Subjects will then be randomized to one of three 12-week treatment arms, 1) Group 1 (Placebo); 2) Group 2 (Depot GnRH agonist (Zoladex) + T + placebo); or 3) Group 3 (Zoladex + T + aromatase inhibitor (anastrozole)). The rationale for this study design is as follows. Under normal physiological conditions, administration of T leads to a concomitant increase in E2 levels due to endogenous conversion by the aromatase enzyme system. Therefore, in order to dissect the relative roles of T and E2 on insulin sensitivity, one group of subjects will receive T in conjunction with the aromatase inhibitor, anastrozole.
At 13 weeks, the entire baseline evaluation including IVGTT, resting metabolic rate and VO2 max, body composition assessment by DEXA and MRI, and muscle biopsy will be repeated. Subjects will return for a follow up visit four weeks later to measure CBC, T and PSA levels, to ensure levels are within the normal range.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome
Keywords
Testosterone, Insulin resistance, Insulin sensitivity, Metabolic disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
72 (Anticipated)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
Testosterone
Intervention Type
Drug
Intervention Name(s)
Anastrozole
Intervention Type
Drug
Intervention Name(s)
Goserelin
Primary Outcome Measure Information:
Title
insulin sensitivity
Title
muscle and body fat distribution
Title
VO2 max
Title
resting metabolic rate
Title
muscle biopsy analysis
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age 50-75 yr
Diagnosis of the metabolic syndrome defined by the American Heart Association/National Heart, Lung, and Blood Institute guidelines as the presence of three or more of the following:
Waist circumference > 102 cm
Serum triglycerides > 150 mg/dL
HDL cholesterol < 40 mg/dL
Blood pressure > 130 mm Hg systolic or 85 mm Hg diastolic, or treatment with anti-hypertensives
Fasting serum glucose > 100 mg/dL
Plasma total testosterone level less than 300 ng/dL (1 SD below the mean for young healthy men)
Stable weight for previous three months (no weight change greater than or equal to +/-10 lbs)
Normal TSH, prolactin and prostate specific antigen (PSA) levels (<2.5 ng/mL)
Exclusion Criteria:
New diagnosis of type 2 diabetes as defined by the ADA criteria: fasting glucose greater than 126 mg/dL or random blood glucose greater than 200 mg/dL on two occasions, or on oral hypoglycemic agents
History of testicular disorders (i.e. cryptorchidism)
History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
History of prostate cancer
History of sleep apnea (subjects will also be excluded if at their baseline assessment they admit to heavy snoring, restless sleep, and/or excessive daytime somnolence)
Symptoms of urinary outflow obstruction (i.e. benign prostatic hypertrophy)
Illicit drug use or heavy alcohol use (>4 drinks/day)
Allergic disorders
Current medications (must exclude individuals taking the following medications: Testosterone, Cimetidine, Spironolactone, Ketoconazole, Finasteride, DHEA, Androstenedione, Oral steroids, GnRH analogs)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William F Crowley, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Frances J Hayes, MD
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Testosterone Effects on Men With the Metabolic Syndrome
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