|
|
Home
Search
Study Topics
Glossary
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
||||||||||||||||||||||||||||||||||||
| Sponsor: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
|---|---|
| Collaborator: |
American Diabetes Association |
| Information provided by: | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| ClinicalTrials.gov Identifier: | NCT00433173 |
Purpose
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.
| Condition | Intervention |
|---|---|
|
Metabolic Syndrome |
Procedure: intravenous glucose tolerance test Drug: testosterone Drug: anastrozole Drug: goserelin acetate implant Procedure: aerobic capacity (VO2 Max) Procedure: MRI Procedure: muscle biopsy Procedure: measurement of resting metabolic rate (energy expenditure) Procedure: Dual energy x-ray absorptiometry Procedure: Fasting oral glucose tolerance test |
| Study Type: | Interventional |
| Study Design: | Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study |
| Official Title: | Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome |
| Estimated Enrollment: | 72 |
| Study Start Date: | May 2006 |
| Estimated Study Completion Date: | March 2011 |
| Estimated Primary Completion Date: | February 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
1: Placebo Comparator
1) Group 1: Placebo
|
Procedure: intravenous glucose tolerance test
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes. At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis. The IVGTT will be administered at baseline and after 3 months.
Procedure: aerobic capacity (VO2 Max)
This test is employed to assess VO2max in all subjects. O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max. This test will be administered at baseline and after 3 months.
Procedure: MRI
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Procedure: muscle biopsy
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied. The muscle biopsy will be performed at baseline and after 3 months.
Procedure: measurement of resting metabolic rate (energy expenditure)
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Procedure: Dual energy x-ray absorptiometry
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50). DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
Procedure: Fasting oral glucose tolerance test
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
|
|
2: Active Comparator
2) Group 2: Depot GnRH agonist (Zoladex) + Testosterone + placebo
|
Procedure: intravenous glucose tolerance test
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes. At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis. The IVGTT will be administered at baseline and after 3 months.
Drug: testosterone
transdermal 7.5 g/per day for 3 months
Drug: goserelin acetate implant
single depot injection 10.8 mg 3 months
Procedure: aerobic capacity (VO2 Max)
This test is employed to assess VO2max in all subjects. O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max. This test will be administered at baseline and after 3 months.
Procedure: MRI
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Procedure: muscle biopsy
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied. The muscle biopsy will be performed at baseline and after 3 months.
Procedure: measurement of resting metabolic rate (energy expenditure)
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Procedure: Dual energy x-ray absorptiometry
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50). DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
Procedure: Fasting oral glucose tolerance test
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
|
|
3: Active Comparator
3) Group 3: (Zoladex + Testosterone + aromatase inhibitor (anastrozole)
|
Procedure: intravenous glucose tolerance test
The IVGTT (70) is a 4 hour study with baseline sampling for insulin and glucose, followed by the administration of 0.3 mg/kg infusion of glucose, and subsequent frequent samples through 180 minutes. At 20 minutes, subjects will receive a 0.03 U/kg infusion of regular human insulin over 45 seconds to enhance the insulin level to better help us assess the impact of insulin on glucose uptake and to facilitate minimal model analysis. The IVGTT will be administered at baseline and after 3 months.
Drug: testosterone
transdermal 7.5 g/per day for 3 months
Drug: anastrozole
tablet (per oral) 10.0 mg/ daily 3 months
Drug: goserelin acetate implant
single depot injection 10.8 mg 3 months
Procedure: aerobic capacity (VO2 Max)
This test is employed to assess VO2max in all subjects. O2 and CO2 will be collected and measured from the expired air during the exercise stress test and used to calculate VO2max. This test will be administered at baseline and after 3 months.
Procedure: MRI
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
Procedure: muscle biopsy
Biopsies (20-50mg) will be obtained from the vastus lateralis muscle under local anesthesia (1% lidocaine) using a 5 mm Bergström needle (65) with suction applied. The muscle biopsy will be performed at baseline and after 3 months.
Procedure: measurement of resting metabolic rate (energy expenditure)
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
Procedure: Dual energy x-ray absorptiometry
Total and regional percent body fat, fat mass, lean tissue mass and bone mineral content will be determined by DEXA (Lunar Prodigy version 8.50). DEXA provides an in vivo assessment of body composition with minimal requirements for subject cooperation and will be employed at baseline and after 3 months.
Procedure: Fasting oral glucose tolerance test
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
|
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 be enrolled. Study subjects will undergo a screening visit to assess eligibility after which a baseline metabolic assessment will be performed including a a fasting oral glucose tolerance test (OGTT) to measure normal glucose and insulin metabolism, 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 (T).
Subjects will then be randomized to one of three 12-week treatment arms, 1) Group 1 (Placebo); 2) Group 2 (Depot GnRH agonist (Zoladex) + Testosterone + placebo); or 3) Group 3 (Zoladex + Testosterone + 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 estradiol (E2) levels due to endogenous conversion by the aromatase enzyme system. Therefore, in order to understand 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 OGTT, 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.
Eligibility| Ages Eligible for Study: | 50 Years to 75 Years |
| Genders Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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:
Exclusion Criteria:
Current medications (must exclude individuals taking the following medications):
Contacts and Locations| United States, Maryland | |
| Johns Hopkins Bayview Medical Center | |
| Baltimore, Maryland, United States, 21224 | |
| United States, Massachusetts | |
| Massachusetts General Hospital | |
| Boston, Massachusetts, United States, 02114 | |
| Principal Investigator: | Frances J Hayes, MD | Massachusetts General Hospital, Boston, MA |
More Information
| Responsible Party: | Massachusetts General Hospital, Boston MA 02114 ( Frances J. Hayes, MD ) |
| Study ID Numbers: | DK71168, NIDDK # 1 RO1 DK071168-01A2 |
| Study First Received: | February 8, 2007 |
| Last Updated: | June 23, 2008 |
| ClinicalTrials.gov Identifier: | NCT00433173 History of Changes |
| Health Authority: | United States: Food and Drug Administration |
|
testosterone insulin sensitivity insulin resistance metabolic disorders |
|
Anastrozole Disease Molecular Mechanisms of Pharmacological Action Antineoplastic Agents, Hormonal Antineoplastic Agents Physiological Effects of Drugs Goserelin Hormones, Hormone Substitutes, and Hormone Antagonists Enzyme Inhibitors Methyltestosterone Hormones |
Pharmacologic Actions Insulin Testosterone 17 beta-cypionate Anabolic Agents Testosterone Hypoglycemic Agents Pathologic Processes Therapeutic Uses Syndrome Aromatase Inhibitors Androgens |
