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- Ensayo clínico NCT00433173
Insulin Sensitivity in Men With the Metabolic Syndrome
Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
- Procedimiento: intravenous glucose tolerance test
- Procedimiento: aerobic capacity (VO2 Max)
- Procedimiento: MRI
- Procedimiento: muscle biopsy
- Procedimiento: measurement of resting metabolic rate (energy expenditure)
- Procedimiento: Dual energy x-ray absorptiometry
- Procedimiento: Fasting oral glucose tolerance test
- Droga: testosterone
- Droga: goserelin acetate implant
- Droga: anastrozole
Descripción detallada
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.
Tipo de estudio
Inscripción (Anticipado)
Fase
- No aplica
Contactos y Ubicaciones
Ubicaciones de estudio
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Maryland
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Baltimore, Maryland, Estados Unidos, 21224
- Johns Hopkins Bayview Medical Center
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Massachusetts
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Boston, Massachusetts, Estados Unidos, 02114
- Massachusetts General Hospital
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-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Triple
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
---|---|
Comparador de placebos: 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.
Otros nombres:
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.
Otros nombres:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Otros nombres:
|
Comparador activo: 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.
Otros nombres:
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.
Otros nombres:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Otros nombres:
transdermal 7.5 g/per day for 3 months
Otros nombres:
single depot injection 10.8 mg 3 months
Otros nombres:
|
Comparador activo: 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.
Otros nombres:
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.
Otros nombres:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Otros nombres:
transdermal 7.5 g/per day for 3 months
Otros nombres:
single depot injection 10.8 mg 3 months
Otros nombres:
tablet (per oral) 10.0 mg/ daily 3 months
Otros nombres:
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
---|---|
insulin sensitivity
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
Medidas de resultado secundarias
Medida de resultado |
Periodo de tiempo |
---|---|
glucose metabolism
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
body composition VO2 max; resting metabolic rate; muscle biopsy analysis
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
VO2 max
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
resting metabolic rate
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
muscle biopsy analysis
Periodo de tiempo: at baseline and after 3 months
|
at baseline and after 3 months
|
Colaboradores e Investigadores
Colaboradores
Investigadores
- Investigador principal: Frances J Hayes, MD, Massachusetts General Hospital
Publicaciones y enlaces útiles
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Anticipado)
Finalización del estudio (Anticipado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Estimar)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Procesos Patológicos
- Trastornos del metabolismo de la glucosa
- Enfermedades metabólicas
- Enfermedades del sistema inmunológico
- Enfermedad
- Hiperinsulinismo
- Hipersensibilidad
- Síndrome
- Síndrome metabólico
- Resistencia a la insulina
- Efectos fisiológicos de las drogas
- Mecanismos moleculares de acción farmacológica
- Inhibidores de enzimas
- Agentes antineoplásicos
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Agentes Antineoplásicos Hormonales
- Antagonistas de hormonas
- Inhibidores de la aromatasa
- Inhibidores de la síntesis de esteroides
- Antagonistas de estrógeno
- Andrógenos
- Goserelina
- Testosterona
- Anastrozol
Otros números de identificación del estudio
- DK71168 (suspended)
- NIDDK # 1 RO1 DK071168-01A2
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .