Protocol Number: 09-DK-0081

Title:

Selective Reduction of Dietary Carbohydrate Versus Fat: Effects on Metabolism, Endocrine Physiology, Brain Activity and Reward Circuitry

Number:

09-DK-0081

Summary:

Background:

- Obesity currently affects one-third of the American population. Recent studies suggest that differences in the areas of the brain that control food intake may make some people more likely to develop obesity. Popular weight-loss strategies often advise reducing dietary carbohydrates or fat, which may affect metabolism, hormones, food preference, and activity in brain regions where perception of food and food intake are regulated.

Objectives:

- To determine how many calories the body needs and the type of fuel (i.e., carbohydrate or fat) the body burns to support bodily functions.

- To measure where chemicals are working in the brain before and after a 12-week weight-loss program.

- To measure blood flow in different regions of the brain during visual and tasting tasks before and after a 12-week weight-loss program.

- To determine how some genes influence food intake.

Eligibility:

- Treatment participants: Obese (body mass index = 30-40 kg/m2) right-handed men and (premenopausal) women between the ages of 18 and 45 years who are otherwise healthy.

- Control participants: Nonobese (body mass index = 18.5-25 kg/m2) right-handed men and (premenopausal) women between the ages of 18 and 45 years.

Design:

- The treatment study consists of four phases, the first of which is the screening visit. The following are descriptions of the other three phases.

- First inpatient visit: Baseline measurements of standard diet, body composition, metabolism, PET/fMRI imaging, and 24-hour energy expenditure (4 days); a reduced fat or reduced carbohydrate diet in addition to the same tests as in the first 4 days (6 days). The final 3 days consist of unrestricted food intake and no testing.

- Second inpatient visit: Baseline measurements of standard diet, body composition, and 24-hour energy expenditure (1 day); a reduced fat or reduced carbohydrate diet in addition to the measurements of body composition, metabolism, PET/fMRI imaging, and 24-hour energy expenditure (6 days). The final 3 days consist of unrestricted food intake and no testing.

- Outpatient diet intervention (12 weeks): A low-calorie diet and physical activity designed to result in loss of at least 5% of body weight by the end of 12 weeks; measurements of body composition, metabolism, PET/fMRI imaging, average daily calories burned, amount of activity, and 24-hour energy expenditure at 2, 6, 10, and 12 weeks; includes up to 4 inpatient days.

- Control participants will visit the research center twice.

- First visit: Physical examination and medical history, measurement of resting metabolic rate and body size, and instructions on completing food and activity logs.

- Preparation for second visit: Eat a standard diet supplied by the research center for 3 days.

- Second visit: Measurement of baseline hormones and other substances in blood; measurement of body weight, composition, and water content; one PET scan; two fMRI scans, one before and one after lunch, during which the participant may be asked to look at images of food or taste small amounts of liquids.

Sponsoring Institute:

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

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

Obese Subjects

INCLUSION CRITERIA:

- Age 18-45 years, male or female

- Body mass less than 350 lbs. (max. weight dictated by table limit for fMRI scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.

- Weight stable (less than plus or minus 5 kg over past 6 months)

- Body mass index 30.0-40.0 kg/m(2)

- Premenopausal (women only)

- Healthy, as determined by medical history and laboratory tests

- Able to complete daily bouts of walking at a moderate rate

- Written informed consent

EXLCUSION CRITERIA:

- Body mass greater than 350 lbs. (max. weight dictated by table limit for fMRI scanner) when acquisition of large bore fMRI is complete, max. wt. limit will increase to 400 lbs.

- BMI less than 30.0 or greater than 40.0 kg/m(2)

- Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, diabetes, thyroid disease)

- Taking any prescription medication (except birth control) or other drug that may influence metabolism (e.g. diet/weight-loss medication)

- Hematocrit less than 34% (women only)

- Hematocrit less than 40% (men only)

- Pregnancy, lactation (women only)

- Allergy to lidocaine or ethanol

- Participating in a regular exercise program (greater than 2h/week of vigorous activity)

- Caffeine consumption greater than 150 mg/day (will be clamped at baseline intake during study)

- Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing), amphetamines, cocaine, heroin, or marijuana over past 6 months

- Past or present history of eating disorder (including binge eating) or psychiatric disease

- Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, multiple food allergies)

- Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.

- Having any metal in their body (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).

- Left-handedness

- Volunteers unwilling or unable to give informed consent

Control Subjects

INCLUSION CRITERIA:

- Age 18-45 years, male or female

- 18.5 kg/m(2) less than BMI less than 25.0 kg/m(2)

- Weight stable (less than plus or minus 5 kg over past 6 months)

- Premenopausal (women only)

- Healthy, as determined by medical history and laboratory tests

- Written informed consent

EXCLUSION CRITERIA:

- BMI less than 18.5 or greater than 25.0 kg/m(2)

- Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer or diabetes)

- Taking any prescription medication (except birth control) or other drug that may influence metabolism (e.g. diet/weight-loss medication)

- Hyperlipidemia (fasting plasma triglyceride concentration greater than 150 mg/dl)

- Hematocrit less than 34% (women only)

- Hematocrit less than 40% (men only)

- Pregnancy, lactation (women only)

- Participating in a regular exercise program (greater than 2h/week of vigorous activity)

- Caffeine consumption greater than 150 mg/day

- Regular use of alcohol (greater than 2 drinks per day), tobacco (smoking or chewing), amphetamines, cocaine, heroin, or marijuana over the past 6 months

- Past or present history of eating disorder (including binge eating) or psychiatric disease

- Volunteers with strict dietary concerns (e.g vegetarian or kosher diet, multiple food allergies)

- Are claustrophobic to a degree that they would feel uncomfortable in the MRI machine.

- Having any metal in their body (for example, pacemakers, metallic prostheses such as cochlear implants or heart valves, shrapnel fragments, etc.).

- Left-handedness

- Volunteers unwilling or unable to give informed consent

Special Instructions:

Currently Not Provided

Keywords:

Obesity

Weight Loss

Carbohydrate

Fat

Macronutrient Balance

Recruitment Keyword(s):

Obesity

Carbohydrate

Fat

Healthy Volunteer

Condition(s):

Obesity

Investigational Drug(s):

[C-11] raclopride

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999 Oct 27;282(16):1523-9.

Allison DB, Zannolli R, Narayan KM. The direct health care costs of obesity in the United States. Am J Public Health. 1999 Aug;89(8):1194-9.

Samaha FF, Iqbal N, Seshadri P, Chicano KL, Daily DA, McGrory J, Williams T, Williams M, Gracely EJ, Stern L. A low-carbohydrate as compared with a low-fat diet in severe obesity. N Engl J Med. 2003 May 22;348(21):2074-81.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
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