ObesityNCT00344266
Gene Expression and Inflammation in Overweight Subjects
An observational study of Obesity and Inflammation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 25 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity, Inflammation, Nutrition Therapy
- How many people
- 144 participants
- Where
- 1 siteUnited States
- Study dates
- 19 Jun 2006to 26 Jun 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 25 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Gene Expression and Release of Inflammatory Mediators in Overweight Subjects Before and After Weight Loss
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.
Read more
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.
Read the 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 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.
- Conditions
- Obesity, Inflammation, Nutrition Therapy
- Keywords
- Obesity, Adipose Tissue, Microarrays, Cytokines, Eicosanoids, Gene Expression, Adipokines, Inflammation, Weight Loss, Lipid Products
- Medical subject headings
- Obesity, Inflammation, Weight Loss
What is being measured
The primary outcome is the main question the study is designed to answer.
Adipokines/cytokines in adipose tissue
Measured: End of study
Gene expression in adipose tissue
Measured: End of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2006 (estimated)
- Study start19 Jun 2006
- Study completion26 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 144 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Kong Y Chen, Ph.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00344266
- Sponsor's protocol ID
- 060183
- Other IDs
- 06-DK-0183
- Status last verified
- 26 Jun 2018
- First submitted
- 23 Jun 2006
- Last updated
- 17 Dec 2019
- Results posted
- No
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. doi: 10.1016/j.bbrc.2005.07.181. Epub 2005 Aug 10.
PubMed 16112645Brown 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.
PubMed 11314930Arner P, Bolinder J. Microdialysis of adipose tissue. J Intern Med. 1991 Oct;230(4):381-6. doi: 10.1111/j.1365-2796.1991.tb00461.x.
PubMed 1919434Agnihothri RV, Courville AB, Linderman JD, Smith S, Brychta R, Remaley A, Chen KY, Simchowitz L, Celi FS. Moderate weight loss is sufficient to affect thyroid hormone homeostasis and inhibit its peripheral conversion. Thyroid. 2014 Jan;24(1):19-26. doi: 10.1089/thy.2013.0055.
PubMed 23902316
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gene Expression and Release of Inflammatory Mediators in Overweight Subjects Before and After Weight Loss
- ClinicalTrials.gov ID
- NCT00344266
- Acronym / sponsor ID
- 060183
- Conditions
- Obesity, Inflammation, Nutrition Therapy
- Keywords
- Obesity, Adipose Tissue, Microarrays, Cytokines, Eicosanoids, Gene Expression, Adipokines, Inflammation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 144 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 19 Jun 2006
- Study completion
- 26 Jun 2018
- First posted
- 26 Jun 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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 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 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 design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 25 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (19 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Adipokines/cytokines in adipose tissue
Time frame: End of study
Gene expression in adipose tissue
Time frame: End of study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2019.
- Background: PubMed 16112645Arita 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. doi: 10.1016/j.bbrc.2005.07.181. Epub 2005 Aug 10.
- Background: PubMed 11314930Brown 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.
- Background: PubMed 1919434Arner P, Bolinder J. Microdialysis of adipose tissue. J Intern Med. 1991 Oct;230(4):381-6. doi: 10.1111/j.1365-2796.1991.tb00461.x.
- Derived from this study: PubMed 23902316Agnihothri RV, Courville AB, Linderman JD, Smith S, Brychta R, Remaley A, Chen KY, Simchowitz L, Celi FS. Moderate weight loss is sufficient to affect thyroid hormone homeostasis and inhibit its peripheral conversion. Thyroid. 2014 Jan;24(1):19-26. doi: 10.1089/thy.2013.0055.
Related trials for Obesity
RecruitingObservational study
Diabetes and Heart Disease Risk in Blacks
Cardiovascular Diseases, Diabetes
Active, not recruitingPhase 2
Effects of Brain Stimulation on Food Intake and Behavioral Weight Loss Treatment
Electric Stimulation Therapy, Obesity
RecruitingObservational study
Children s Growth and Behavior Study
Obesity, Eating Behaviors
Recruiting
Tailoring Mobile Health Technology to Reduce Obesity and Improve Cardiovascular Health in Resource-Limited Neighborhood Environments
Obesity
Active, not recruiting
Mindfulness Based Eating Awareness Training for Bariatric Surgery Patients
Obesity, Morbid, Eating Disorder Symptom
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kong Y Chen, Ph.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Obesity and Inflammation, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 17 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adipokines/cytokines in adipose tissue (time frame: End of study). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00344266, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Dec 2019; AzTrials last refreshed its copy on 30 Oct 2026.