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Insulin Sensitivity in Men With the Metabolic Syndrome
Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
- Procedure: intravenous glucose tolerance test
- 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
- Geneesmiddel: testosterone
- Geneesmiddel: goserelin acetate implant
- Geneesmiddel: anastrozole
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Verwacht)
Fase
- Niet toepasbaar
Contacten en locaties
Studie Locaties
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Maryland
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Baltimore, Maryland, Verenigde Staten, 21224
- Johns Hopkins Bayview Medical Center
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Massachusetts
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Boston, Massachusetts, Verenigde Staten, 02114
- Massachusetts General Hospital
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Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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
- Contraindication to stress testing
- Contraindication to MRI scanning (Central nervous system aneurysm clips; Implanted neural stimulator; Implanted cardiac pacemaker or defibrillator; Cochlear implant; Ocular foreign body (e.g. metal shavings); Insulin pump; Metal shrapnel or bullet)
- History of testicular disorders (i.e. cryptorchidism)
- History of bleeding disorders (i.e. thrombocytopenia) or baseline hemoglobin levels less than 12g/dL
- History of metabolic bone disease (osteoporosis, osteomalacia)
- 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
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Verdrievoudigen
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
---|---|
Placebo-vergelijker: 1
1) Group 1: Placebo
|
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.
Andere namen:
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.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
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.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
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.
Andere namen:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andere namen:
|
Actieve vergelijker: 2
2) Group 2: Depot GnRH agonist (Zoladex) + Testosterone + placebo
|
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.
Andere namen:
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.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
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.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
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.
Andere namen:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andere namen:
transdermal 7.5 g/per day for 3 months
Andere namen:
single depot injection 10.8 mg 3 months
Andere namen:
|
Actieve vergelijker: 3
3) Group 3: (Zoladex + Testosterone + aromatase inhibitor (anastrozole)
|
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.
Andere namen:
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.
1H-MR spectroscopy will be performed to measure IMCL at baseline and after 3 months.
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.
Energy expenditure in the form of resting metabolic rate (RMR) will be measured via a metabolic monitor at baseline and after 3 months.
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.
Andere namen:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andere namen:
transdermal 7.5 g/per day for 3 months
Andere namen:
single depot injection 10.8 mg 3 months
Andere namen:
tablet (per oral) 10.0 mg/ daily 3 months
Andere namen:
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
insulin sensitivity
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
Secundaire uitkomstmaten
Uitkomstmaat |
Tijdsspanne |
---|---|
glucose metabolism
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
body composition VO2 max; resting metabolic rate; muscle biopsy analysis
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
VO2 max
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
resting metabolic rate
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
muscle biopsy analysis
Tijdsspanne: at baseline and after 3 months
|
at baseline and after 3 months
|
Medewerkers en onderzoekers
Medewerkers
Onderzoekers
- Hoofdonderzoeker: Frances J Hayes, MD, Massachusetts General Hospital
Publicaties en nuttige links
Studie record data
Bestudeer belangrijke data
Studie start
Primaire voltooiing (Verwacht)
Studie voltooiing (Verwacht)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Schatting)
Updates van studierecords
Laatste update geplaatst (Schatting)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Aanvullende relevante MeSH-voorwaarden
- Pathologische processen
- Glucosemetabolismestoornissen
- Metabole ziekten
- Ziekten van het immuunsysteem
- Ziekte
- Hyperinsulinisme
- Overgevoeligheid
- Syndroom
- Metaboolsyndroom
- Insuline-resistentie
- Fysiologische effecten van medicijnen
- Moleculaire mechanismen van farmacologische werking
- Enzymremmers
- Antineoplastische middelen
- Hormonen
- Hormonen, hormoonvervangers en hormoonantagonisten
- Antineoplastische middelen, hormonaal
- Hormoon antagonisten
- Aromatase-remmers
- Steroïde syntheseremmers
- Oestrogeen antagonisten
- Androgenen
- Gosereline
- Testosteron
- Anastrozol
Andere studie-ID-nummers
- DK71168 (suspended)
- NIDDK # 1 RO1 DK071168-01A2
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