Ignite Creation Date:
2024-05-05 @ 11:43 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00111956
Status:
COMPLETED
Last Update Posted:
2017-10-06
First Post:
2005-05-26
Brief Title:
Effects of Tumor Necrosis Factor TNF-Alpha Antagonism in Patients With Metabolic Syndrome
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Study Overview
Official Title:
Effects of Tumor Necrosis Factor TNF-Alpha Antagonism in Patients With Metabolic Syndrome
Status:
COMPLETED
Status Verified Date:
2017-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin that may be mediated in part by TNF production from abdominal fat We reasoned that an anti-TNF agent would reduce C-reactive protein CRP and increase adiponectin improving the inflammatory milieu associated with metabolic syndrome
Detailed Description:
Screening visit 1
Fifty six patients will be randomized to receive etanercept or identical placebo During the screening visit after informed consent is obtained subjects will undergo a medical history and physical exam which will include vital signs weight abdominal girth measurements and an evaluation for signs of underlying infection A purified protein derivative PPD of 5 tuberculin units TU 01 milliliter of 5 TU01 ml solution will be intradermally placed to test for the presence of tuberculosis TB Fasting blood work will include a complete blood count CBC glucose insulin a cholesterol panel and urine pregnancy test Subjects will be shown what a subcutaneous injection entails using placebo Patients will be selected based on their laboratory results abdominal girth measurements and PPD negativity 48 hrs after placement
Screening visit 2
Subjects will return 48 hours after their first screening visit for evaluation of their PPD test In the event of a positive PPD subjects will be excluded from the study and their primary care physicians will be notified of their test result
Day 1 visit
Subjects will report to Massachusetts General Hospital MGH or Massachusetts Institute of Technology MIT Clinical Research Center GCRC after an overnight fast Fasting blood work will be obtained to test for CRP adiponectin IL-6 TNF-alpha TNF-alpha receptor 1 TNF-alpha receptor 2 free fatty acids glucose insulin and a cholesterol panel and CBC A urine pregnancy test will be done Patients will be asked to recall the food they consumed over the past 24 hours A bionutritionist will measure height weight waist hip chest arm neck and thigh circumference Subjects will be instructed to practice adequate birth control throughout the study Serum will be stored for etanercept antibody testing
Subjects will then undergo an insulin modified frequently sampled intravenous IV glucose tolerance test FSIGT as initially developed by Bergman et al
Dual energy x-ray absorptiometry DEXA Hologic QDR 4500 will be used to determine whole body and regional fat The technique has a precision error 1 SD of 3 for whole body fat and 15 for lean mass Subjects will also undergo a single thin-slice CT scan of the abdomen at L4 vertebral body to determine visceral and subcutaneous fat area
Indirect calorimetry for the measurement of resting energy expenditure indirect calorimetry using the Deltatrac instrument Sensormedics Anaheim CA will be carried out
Drug administration
Patients will be given a total of either etanercept 50 mg subcutaneously or placebo subcutaneously at the GCRC at the end of their visit They will receive this in two injections of 25 mg each one given immediately following the other at different body sites Etanercept will be supplied as a sterile white preservative-free lyophilized powder The pharmacy will reconstitute it with 1 mL of the supplied sterile bacteriostatic water for injection BWFI United States Pharmacopeia USP containing 09 benzyl alcohol Each vial of etanercept contains 25 mg etanercept 40 mg mannitol 10 mg sucrose and 12 mg tromethamine Subjects will receive the 50 mg dose of etanercept or placebo once a week given as two 25 mg injections one immediately following the other at different body sites at each of their ensuing three visits to the GCRC on Visit Day 8 Visit Day 15 and Visit Day 22 Subjects will be monitored for 30 minutes after the injection of study drug at each visit The skin injection site will be observed and their vital signs will be taken If a subject has a significant exposure to varicella virus during the study transient termination of the study will be considered
Day 8 visit Day 15 visit Day 22 visit
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast Each subject will undergo a history and physical exam to assess for safety and compliance Fasting blood work will be obtained A bionutritionist will measure subjects height weight hip and waist circumference and calculate a waist to hip ratio They will receive 50 mg of either etanercept or placebo given as two 25 mg doses subcutaneously at different body sites
Day 25 visit
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast Each subject will undergo a history and physical exam to assess for safety and compliance Blood work a urine pregnancy test and 24 hour food recall will be collected identical to that on Day 1 visit Anthropomorphic measurements will be the same as the Day 1 visit Subjects will undergo an intravenous glucose tolerance test IVGTT identical to that on the Day 1 visit Subjects will undergo a DEXA bioelectric impedance analysis BIA and CT and indirect calorimetry identical to those on the Day 1 visit No study drug will be administered at this visit
Fifty six patients will be randomized to receive etanercept or identical placebo During the screening visit after informed consent is obtained subjects will undergo a medical history and physical exam which will include vital signs weight abdominal girth measurements and an evaluation for signs of underlying infection A purified protein derivative PPD of 5 tuberculin units TU 01 milliliter of 5 TU01 ml solution will be intradermally placed to test for the presence of tuberculosis TB Fasting blood work will include a complete blood count CBC glucose insulin a cholesterol panel and urine pregnancy test Subjects will be shown what a subcutaneous injection entails using placebo Patients will be selected based on their laboratory results abdominal girth measurements and PPD negativity 48 hrs after placement
Screening visit 2
Subjects will return 48 hours after their first screening visit for evaluation of their PPD test In the event of a positive PPD subjects will be excluded from the study and their primary care physicians will be notified of their test result
Day 1 visit
Subjects will report to Massachusetts General Hospital MGH or Massachusetts Institute of Technology MIT Clinical Research Center GCRC after an overnight fast Fasting blood work will be obtained to test for CRP adiponectin IL-6 TNF-alpha TNF-alpha receptor 1 TNF-alpha receptor 2 free fatty acids glucose insulin and a cholesterol panel and CBC A urine pregnancy test will be done Patients will be asked to recall the food they consumed over the past 24 hours A bionutritionist will measure height weight waist hip chest arm neck and thigh circumference Subjects will be instructed to practice adequate birth control throughout the study Serum will be stored for etanercept antibody testing
Subjects will then undergo an insulin modified frequently sampled intravenous IV glucose tolerance test FSIGT as initially developed by Bergman et al
Dual energy x-ray absorptiometry DEXA Hologic QDR 4500 will be used to determine whole body and regional fat The technique has a precision error 1 SD of 3 for whole body fat and 15 for lean mass Subjects will also undergo a single thin-slice CT scan of the abdomen at L4 vertebral body to determine visceral and subcutaneous fat area
Indirect calorimetry for the measurement of resting energy expenditure indirect calorimetry using the Deltatrac instrument Sensormedics Anaheim CA will be carried out
Drug administration
Patients will be given a total of either etanercept 50 mg subcutaneously or placebo subcutaneously at the GCRC at the end of their visit They will receive this in two injections of 25 mg each one given immediately following the other at different body sites Etanercept will be supplied as a sterile white preservative-free lyophilized powder The pharmacy will reconstitute it with 1 mL of the supplied sterile bacteriostatic water for injection BWFI United States Pharmacopeia USP containing 09 benzyl alcohol Each vial of etanercept contains 25 mg etanercept 40 mg mannitol 10 mg sucrose and 12 mg tromethamine Subjects will receive the 50 mg dose of etanercept or placebo once a week given as two 25 mg injections one immediately following the other at different body sites at each of their ensuing three visits to the GCRC on Visit Day 8 Visit Day 15 and Visit Day 22 Subjects will be monitored for 30 minutes after the injection of study drug at each visit The skin injection site will be observed and their vital signs will be taken If a subject has a significant exposure to varicella virus during the study transient termination of the study will be considered
Day 8 visit Day 15 visit Day 22 visit
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast Each subject will undergo a history and physical exam to assess for safety and compliance Fasting blood work will be obtained A bionutritionist will measure subjects height weight hip and waist circumference and calculate a waist to hip ratio They will receive 50 mg of either etanercept or placebo given as two 25 mg doses subcutaneously at different body sites
Day 25 visit
Subjects will report to MGH or MIT Clinical Research Center after an overnight fast Each subject will undergo a history and physical exam to assess for safety and compliance Blood work a urine pregnancy test and 24 hour food recall will be collected identical to that on Day 1 visit Anthropomorphic measurements will be the same as the Day 1 visit Subjects will undergo an intravenous glucose tolerance test IVGTT identical to that on the Day 1 visit Subjects will undergo a DEXA bioelectric impedance analysis BIA and CT and indirect calorimetry identical to those on the Day 1 visit No study drug will be administered at this visit
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| F32DK068902 | NIH | None | httpsreporternihgovquickSearchF32DK068902 |