Gene Expression and Inflammation in Overweight Subjects - Full Text View

Sponsor:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:	NCT00344266

Purpose

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 24.9. 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 ...

Condition
Overweight Weight Loss

Study Type:	Observational
Official Title:	Gene Expression and Release of Inflammatory Mediators in Overweight Subjects Before and After Weight Loss

Resource links provided by NLM:

MedlinePlus related topics: Diets Obesity Weight Control

U.S. FDA Resources

Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment:	250
Study Start Date:	June 2006
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Detailed Description:

Obesity is a global public health problem of epidemic proportions. It is the source of considerable morbidity and early mortality in the U.S. 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 mediators/cytokines, and novel lipid products will be analyzed using sensitive Liquid Chromatography-Mass Spectrometry and ELISA methods.

The study design incorporates two basic objectives:

Comparison of Non-Overweight Controls vs. Overweight Subjects at Baseline and
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 19.0 - 24.9) and 80 Overweight Subjects (BMI 25.0 - 45.0) 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 altered gene expression and release of inflammatory cytokines and other mediators in obesity and the dynamic series of events that take place with weight loss. 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.

Eligibility

Ages Eligible for Study:	25 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

INCLUSION CRITERIA:
Age 25-45 years, male or female
BMI 25.0-45.0 kg/m(2) for Overweight Subjects and 19.0-24.9 kg/m(2) for Non-Overweight Controls
Healthy, as determined by medical history and laboratory tests
Written informed consent

EXCLUSION CRITERIA:

BMI less than 19.0 or greater than 45.0 kg/m(2)
History or symptoms compatible with cardiovascular disease, including arrhythmias and syncopal episodes, or use of prescription medications for heart conditions, strokes, or peripheral vascular disease
Allergy to lidocaine
Pregnancy or breastfeeding
Menopause or peri-menopausal period (FSH greater than 15 mIU/ml)
Use of hormonal contraceptives or estrogen replacement therapy
Alcohol (more than 2 drinks per day or CAGE greater than 2 questions and/or current/regular use of drugs such as amphetamines, cocaine, heroin, or marijuana
Current use of tobacco products (smoking or chewing)
History of Diabetes Mellitus, either type 1 or 2, or Fasting Glucose greater than 126 mg/dl
Use of cholesterol- or lipid-lowering drugs, or fasting serum lipids in range requiring medication per Adult Treatment Panel III recommendations of the National Cholesterol Education Program
Liver disease or ALT serum level greater than two-fold above the laboratory reference standard
Renal insufficiency or estimated creatinine clearance less than or equal to 50 ml/min
Current use of medications, dietary supplements (including fish oils), or alternative therapies known to alter thyroid function with the exception of occasional use of NSAIDs (3 tablets/week maximum) and Benzodiazepines; use of NSAIDs in the 10 days preceding the hospital admissions
Current history, symptoms, or behavior compatible with psychiatric disorders or therapy with psychotropic medications that would be incompatible with safe and successful participation in this study
History of drug or alcohol abuse within the last 5 years; current use of drugs or alcohol
Keloid formation (relative to subcutaneous adipose tissue biopsies)
Hypo- or hyperthyroidism (TSH greater than or equal to 10; less than or equal to 0.1 mIU/L)
Blood pressure greater than 160/95 mm Hg or use of prescription medications for treatment of hypertension
Cushing Syndrome

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00344266

Contacts

Contact: Patient Recruitment and Public Liaison Office	(800) 411-1222	prpl@mail.cc.nih.gov
Contact: TTY	1-866-411-1010

Locations

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike	Recruiting
Bethesda, Maryland, United States, 20892

Sponsors and Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

More Information

Additional Information:

NIH Clinical Center Detailed Web Page This link exits the ClinicalTrials.gov site

Publications:

Arita M, Clish CB, Serhan CN. The contributions of aspirin and microbial oxygenase to the biosynthesis of anti-inflammatory resolvins: novel oxygenase products from omega-3 polyunsaturated fatty acids. Biochem Biophys Res Commun. 2005 Dec 9;338(1):149-57. Epub 2005 Aug 10. Review.

Brown RL, Leonard T, Saunders LA, Papasouliotis O. A two-item conjoint screen for alcohol and other drug problems. J Am Board Fam Pract. 2001 Mar-Apr;14(2):95-106.

Arner P, Bolinder J. Microdialysis of adipose tissue. J Intern Med. 1991 Oct;230(4):381-6. Review.

Study ID Numbers:	060183, 06-DK-0183
Study First Received:	June 23, 2006
Last Updated:	November 24, 2009
ClinicalTrials.gov Identifier:	NCT00344266 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Obesity
Adipose Tissue
Microarrays
Cytokines
Eicosanoids
Gene Expression

Adipokines
Inflammation
Weight Loss
Lipid Products
Obesity
Weight Loss

Additional relevant MeSH terms:

Body Weight
Signs and Symptoms
Pathologic Processes
Weight Loss

Body Weight Changes
Overweight
Inflammation

ClinicalTrials.gov processed this record on November 27, 2009