- ICH GCP
- US Clinical Trials Registry
- Klinisk utprøving NCT00433173
Insulin Sensitivity in Men With the Metabolic Syndrome
Effect of Increasing Testosterone on Insulin Sensitivity in Men With the Metabolic Syndrome
Studieoversikt
Status
Forhold
Intervensjon / Behandling
- Fremgangsmåte: intravenous glucose tolerance test
- Fremgangsmåte: aerobic capacity (VO2 Max)
- Fremgangsmåte: MRI
- Fremgangsmåte: muscle biopsy
- Fremgangsmåte: measurement of resting metabolic rate (energy expenditure)
- Fremgangsmåte: Dual energy x-ray absorptiometry
- Fremgangsmåte: Fasting oral glucose tolerance test
- Legemiddel: testosterone
- Legemiddel: goserelin acetate implant
- Legemiddel: anastrozole
Detaljert beskrivelse
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
Registrering (Forventet)
Fase
- Ikke aktuelt
Kontakter og plasseringer
Studiesteder
-
-
Maryland
-
Baltimore, Maryland, Forente stater, 21224
- Johns Hopkins Bayview Medical Center
-
-
Massachusetts
-
Boston, Massachusetts, Forente stater, 02114
- Massachusetts General Hospital
-
-
Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
---|---|
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.
Andre navn:
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.
Andre navn:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andre navn:
|
Aktiv 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.
Andre navn:
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.
Andre navn:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andre navn:
transdermal 7.5 g/per day for 3 months
Andre navn:
single depot injection 10.8 mg 3 months
Andre navn:
|
Aktiv 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.
Andre navn:
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.
Andre navn:
To examine glucose and insulin metabolism a standard 75g OGTT will be conducted at baseline and after 3 months.
Andre navn:
transdermal 7.5 g/per day for 3 months
Andre navn:
single depot injection 10.8 mg 3 months
Andre navn:
tablet (per oral) 10.0 mg/ daily 3 months
Andre navn:
|
Hva måler studien?
Primære resultatmål
Resultatmål |
Tidsramme |
---|---|
insulin sensitivity
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
Sekundære resultatmål
Resultatmål |
Tidsramme |
---|---|
glucose metabolism
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
body composition VO2 max; resting metabolic rate; muscle biopsy analysis
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
VO2 max
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
resting metabolic rate
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
muscle biopsy analysis
Tidsramme: at baseline and after 3 months
|
at baseline and after 3 months
|
Samarbeidspartnere og etterforskere
Samarbeidspartnere
Etterforskere
- Hovedetterforsker: Frances J Hayes, MD, Massachusetts General Hospital
Publikasjoner og nyttige lenker
Studierekorddatoer
Studer hoveddatoer
Studiestart
Primær fullføring (Forventet)
Studiet fullført (Forventet)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Anslag)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Anslag)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Ytterligere relevante MeSH-vilkår
- Patologiske prosesser
- Glukosemetabolismeforstyrrelser
- Metabolske sykdommer
- Sykdommer i immunsystemet
- Sykdom
- Hyperinsulinisme
- Overfølsomhet
- Syndrom
- Metabolsk syndrom
- Insulinresistens
- Fysiologiske effekter av legemidler
- Molekylære mekanismer for farmakologisk virkning
- Enzymhemmere
- Antineoplastiske midler
- Hormoner
- Hormoner, hormonsubstitutter og hormonantagonister
- Antineoplastiske midler, hormonelle
- Hormonantagonister
- Aromatasehemmere
- Steroidesyntesehemmere
- Østrogenantagonister
- Androgener
- Goserelin
- Testosteron
- Anastrozol
Andre studie-ID-numre
- DK71168 (suspended)
- NIDDK # 1 RO1 DK071168-01A2
Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .
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