| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Overweight - Weight Loss |
| Purpose: |
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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 ...
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| Study summary: |
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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:
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 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. |
| Criteria: |
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- 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 |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 21, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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