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- Klinische Studie NCT00433173
Insulin Sensitivity in Men With the Metabolic Syndrome
Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome
Studienübersicht
Status
Bedingungen
Intervention / Behandlung
- Verfahren: intravenous glucose tolerance test
- Verfahren: aerobic capacity (VO2 Max)
- Verfahren: MRI
- Verfahren: muscle biopsy
- Verfahren: measurement of resting metabolic rate (energy expenditure)
- Verfahren: Dual energy x-ray absorptiometry
- Verfahren: Fasting oral glucose tolerance test
- Arzneimittel: testosterone
- Arzneimittel: goserelin acetate implant
- Arzneimittel: anastrozole
Detaillierte Beschreibung
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.
Studientyp
Einschreibung (Voraussichtlich)
Phase
- Unzutreffend
Kontakte und Standorte
Studienorte
-
-
Maryland
-
Baltimore, Maryland, Vereinigte Staaten, 21224
- Johns Hopkins Bayview Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, Vereinigte Staaten, 02114
- Massachusetts General Hospital
-
-
Teilnahmekriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: Zufällig
- Interventionsmodell: Parallele Zuordnung
- Maskierung: Verdreifachen
Waffen und Interventionen
Teilnehmergruppe / Arm |
Intervention / Behandlung |
---|---|
Placebo-Komparator: 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:
|
Aktiver Komparator: 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:
|
Aktiver Komparator: 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:
|
Was misst die Studie?
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
insulin sensitivity
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Zeitfenster |
---|---|
glucose metabolism
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
body composition VO2 max; resting metabolic rate; muscle biopsy analysis
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
VO2 max
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
resting metabolic rate
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
muscle biopsy analysis
Zeitfenster: at baseline and after 3 months
|
at baseline and after 3 months
|
Mitarbeiter und Ermittler
Mitarbeiter
Ermittler
- Hauptermittler: Frances J Hayes, MD, Massachusetts General Hospital
Publikationen und hilfreiche Links
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn
Primärer Abschluss (Voraussichtlich)
Studienabschluss (Voraussichtlich)
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Schätzen)
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Schätzen)
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Schlüsselwörter
Zusätzliche relevante MeSH-Bedingungen
- Pathologische Prozesse
- Störungen des Glukosestoffwechsels
- Stoffwechselerkrankungen
- Erkrankungen des Immunsystems
- Erkrankung
- Hyperinsulinismus
- Überempfindlichkeit
- Syndrom
- Metabolisches Syndrom
- Insulinresistenz
- Physiologische Wirkungen von Arzneimitteln
- Molekulare Mechanismen der pharmakologischen Wirkung
- Enzym-Inhibitoren
- Antineoplastische Mittel
- Hormone
- Hormone, Hormonersatzstoffe und Hormonantagonisten
- Antineoplastische Mittel, hormonell
- Hormonantagonisten
- Aromatasehemmer
- Steroidsynthese-Inhibitoren
- Östrogen Antagonisten
- Androgene
- Goserelin
- Testosteron
- Anastrozol
Andere Studien-ID-Nummern
- DK71168 (suspended)
- NIDDK # 1 RO1 DK071168-01A2
Diese Informationen wurden ohne Änderungen direkt von der Website clinicaltrials.gov abgerufen. Wenn Sie Ihre Studiendaten ändern, entfernen oder aktualisieren möchten, wenden Sie sich bitte an register@clinicaltrials.gov. Sobald eine Änderung auf clinicaltrials.gov implementiert wird, wird diese automatisch auch auf unserer Website aktualisiert .
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