Ignite Creation Date:
2024-05-05 @ 4:55 PM
Last Modification Date:
2024-10-26 @ 9:25 AM
Study NCT ID:
NCT00344266
Status:
COMPLETED
Last Update Posted:
2019-12-17
First Post:
2006-06-23
Brief Title:
Gene Expression and Inflammation in Overweight Subjects
Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases NIDDK
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Gene Expression and Release of Inflammatory Mediators in Overweight Subjects Before and After Weight Loss
Status:
COMPLETED
Status Verified Date:
2018-06-26
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This study will look at gene expression whether particular sets of genes are activated turned on or deactivated turned off in overweight people as compared to non-overweight individuals It will also investigate the potential role of inflammatory and protective substances that are produced naturally by the body within fat tissue Findings from the study may lead to the development of ways to predict who will respond best to diet therapy
Healthy individuals between 25 and 45 years of age may be eligible for this study Overweight subjects must have a BMI of 25 to 40 and non-overweight control subjects a BMI of 19 to 249 Candidates are screened with a medical history physical examination blood tests and electrocardiogram EKG They are instructed to record their dietary intake for a 3-day period and to collect their urine for a 24-hour interval
Participants have their food records reviewed a week after the screening visit They are then scheduled for an overnight admission to the Clinical Center Non-overweight subjects have one or two inpatient stays overweight subjects have six inpatient stays plus frequent nutrition counseling sessions During the 2-day hospital admissions the following studies are performed
DEXA scan to determine the percentage of body fat tissue The subject lies on a table for about 15 to 60 minutes while the body composition is measured with very low-dose x-rays
Single-slice CT scan to compare the amount of fat tissue under the skin with that in the abdomen The subject lies on a table for about 5 to 10 minutes while the CT scanner measures body composition with very low-dose x-rays
Subcutaneous fat microdialysis to investigate how weight loss affects the activity of fat tissue A small tube catheter is placed into the fat tissue under the skin of the abdomen after numbing the skin with a local anesthetic Fluid samples are collected through the tube The procedure lasts overnight In five non-overweight controls a small amount of a substance called leukotriene B4 is put into their fat tissue to help adjust the instruments used in the study
Air-displacement plethysmography to measure body composition Subjects wear close-fitting clothing and enter a small capsule called a Bod-Pod They breathe normally in the capsule while their body fat composition is studied
Blood tests Blood samples are drawn to analyze thyroid hormones lipids glucose electrolytes clotting factors kidney function red cells and DNA
Euglycemic-hyperinsulinemic clamp to measure the effects of insulin in the body and to derive an index of insulin-sensitivity Catheters are placed in a vein in an arm and in a vein in the hand on the other side of the body Insulin and glucose are infused through the catheter in the arm and blood samples are drawn from the catheter in the hand every 5 minutes to measure glucose levels The test lasts about 2 hours
Subcutaneous fat biopsy to find out how weight loss affects fat tissue characteristics gene regulation and the ability to store glucose A small sample of fat tissue is obtained from the skin of the abdomen after numbing the area with an anesthetic
Nutrition counseling for overweight subjects A nutritionist reviews the food record and designs a personalized diet for each participant
Weight loss intervention for overweight subjects In addition to individual nutritional counseling group sessions are provided every 2 weeks during the first 3 months of the study and then every month
Healthy individuals between 25 and 45 years of age may be eligible for this study Overweight subjects must have a BMI of 25 to 40 and non-overweight control subjects a BMI of 19 to 249 Candidates are screened with a medical history physical examination blood tests and electrocardiogram EKG They are instructed to record their dietary intake for a 3-day period and to collect their urine for a 24-hour interval
Participants have their food records reviewed a week after the screening visit They are then scheduled for an overnight admission to the Clinical Center Non-overweight subjects have one or two inpatient stays overweight subjects have six inpatient stays plus frequent nutrition counseling sessions During the 2-day hospital admissions the following studies are performed
DEXA scan to determine the percentage of body fat tissue The subject lies on a table for about 15 to 60 minutes while the body composition is measured with very low-dose x-rays
Single-slice CT scan to compare the amount of fat tissue under the skin with that in the abdomen The subject lies on a table for about 5 to 10 minutes while the CT scanner measures body composition with very low-dose x-rays
Subcutaneous fat microdialysis to investigate how weight loss affects the activity of fat tissue A small tube catheter is placed into the fat tissue under the skin of the abdomen after numbing the skin with a local anesthetic Fluid samples are collected through the tube The procedure lasts overnight In five non-overweight controls a small amount of a substance called leukotriene B4 is put into their fat tissue to help adjust the instruments used in the study
Air-displacement plethysmography to measure body composition Subjects wear close-fitting clothing and enter a small capsule called a Bod-Pod They breathe normally in the capsule while their body fat composition is studied
Blood tests Blood samples are drawn to analyze thyroid hormones lipids glucose electrolytes clotting factors kidney function red cells and DNA
Euglycemic-hyperinsulinemic clamp to measure the effects of insulin in the body and to derive an index of insulin-sensitivity Catheters are placed in a vein in an arm and in a vein in the hand on the other side of the body Insulin and glucose are infused through the catheter in the arm and blood samples are drawn from the catheter in the hand every 5 minutes to measure glucose levels The test lasts about 2 hours
Subcutaneous fat biopsy to find out how weight loss affects fat tissue characteristics gene regulation and the ability to store glucose A small sample of fat tissue is obtained from the skin of the abdomen after numbing the area with an anesthetic
Nutrition counseling for overweight subjects A nutritionist reviews the food record and designs a personalized diet for each participant
Weight loss intervention for overweight subjects In addition to individual nutritional counseling group sessions are provided every 2 weeks during the first 3 months of the study and then every month
Detailed Description:
Obesity is a global public health problem of epidemic proportions It is the source of considerable morbidity and early mortality in the US and is associated with increased risk of diabetes hypertension cardiovascular disease and cancer
In recent years new and evolving concepts have emerged regarding obesity as a chronic endocrine disorder of inflammation Moreover a growing body of evidence indicates that obesity alters the profile of a constellation of genes and that some changes in biomarkers of inflammation and gene expression can be reversed by weight loss
In this clinical protocol we propose to test the idea that a particular set of genes is activated or deactivated in Overweight Subjects using standard microarray techniques on samples of subcutaneous adipose tissue derived from biopsies In addition we will study the local adipose tissue microenvironment by means of microdialysis The role of a number of adipokines inflammatory mediatorscytokines and novel lipid products will be analyzed using sensitive Liquid Chromatography-Mass Spectrometry and ELISA methods
The study design incorporates two basic objectives
1 Comparison of Non-Overweight Controls vs Overweight Subjects at Baseline and
2 Correlation of changes in Overweight patients over time as they lose weight through a calorie-restricted diet
To these ends 30 Non-Overweight Controls BMI 190 249 and 80 Overweight Subjects BMI 250 450 will be enrolled Baseline studies to be obtained on all participants include blood tests anthropometric indices body composition by air-displacement plethysmography indirect calorimetry intravenous glucose tolerance test as an index of insulin sensitivity subcutaneous adipose tissue microdialysis and subcutaneous adipose tissue biopsy These procedures will require an overnight hospital admission to the Clinical Center Overweight Subjects will then be prescribed a calorie-restricted diet and followed for one year They will undergo repeat studies at regular 3-month intervals to assess serial changes in the various parameters and to provide correlative data with the degree and rate of weight loss achieved
Taken together these studies should shed light and provide fundamental insights into the nature of the altered gene expression and release of inflammatory cytokines and other mediators that characterize the overweight state and the dynamic series of events that take place when dietary intervention leads to weight loss It is anticipated that a number of these changes will relate to macrophages and known inflammatory markers though doubtless there are other important leads yet to be discovered Thus our hope is that such studies will ultimately lead to the identification of novel genes that underlie the important metabolic derangements associated with obesity and their response to different treatment modalities
In recent years new and evolving concepts have emerged regarding obesity as a chronic endocrine disorder of inflammation Moreover a growing body of evidence indicates that obesity alters the profile of a constellation of genes and that some changes in biomarkers of inflammation and gene expression can be reversed by weight loss
In this clinical protocol we propose to test the idea that a particular set of genes is activated or deactivated in Overweight Subjects using standard microarray techniques on samples of subcutaneous adipose tissue derived from biopsies In addition we will study the local adipose tissue microenvironment by means of microdialysis The role of a number of adipokines inflammatory mediatorscytokines and novel lipid products will be analyzed using sensitive Liquid Chromatography-Mass Spectrometry and ELISA methods
The study design incorporates two basic objectives
1 Comparison of Non-Overweight Controls vs Overweight Subjects at Baseline and
2 Correlation of changes in Overweight patients over time as they lose weight through a calorie-restricted diet
To these ends 30 Non-Overweight Controls BMI 190 249 and 80 Overweight Subjects BMI 250 450 will be enrolled Baseline studies to be obtained on all participants include blood tests anthropometric indices body composition by air-displacement plethysmography indirect calorimetry intravenous glucose tolerance test as an index of insulin sensitivity subcutaneous adipose tissue microdialysis and subcutaneous adipose tissue biopsy These procedures will require an overnight hospital admission to the Clinical Center Overweight Subjects will then be prescribed a calorie-restricted diet and followed for one year They will undergo repeat studies at regular 3-month intervals to assess serial changes in the various parameters and to provide correlative data with the degree and rate of weight loss achieved
Taken together these studies should shed light and provide fundamental insights into the nature of the altered gene expression and release of inflammatory cytokines and other mediators that characterize the overweight state and the dynamic series of events that take place when dietary intervention leads to weight loss It is anticipated that a number of these changes will relate to macrophages and known inflammatory markers though doubtless there are other important leads yet to be discovered Thus our hope is that such studies will ultimately lead to the identification of novel genes that underlie the important metabolic derangements associated with obesity and their response to different treatment modalities
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| 06-DK-0183 | None | None | None |