Reduced Carbohydrate Versus Fat in Obese Subjects

NCT00846040 | Completed Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: 09008109-DK-0081
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Popular weight loss strategies often involve reducing an individual's consumption of carbohydrates or fat. However, no controlled study has been carried out to evaluate the effects of reducing carbohydrate versus fat consumption while keeping the other nutrients at standard levels to maintain an individual's weight. Researchers are interested in investigating how different restrictions of carbohydrates or fats affect the many processes involved in weight loss, including brain activity and blood and brain chemical composition.

Conditions

Obesity

Keywords

Obesity; Weight Loss; Carbohydrate; Fat; Macronutrient Balance; Healthy Volunteer

Outcome Measures

Primary Outcomes (1)

• Change in Respiratory Quotient (RQ)

  Respiratory quotient was calculated as the ratio of carbon dioxide production to oxygen consumption as measured in a metabolic chamber for at least 23 continuous hours on days 2 and 5 of the baseline diet and days 1, 4, and 6 of the reduced-energy diets.

  Baseline and day 14

Secondary Outcomes (5)

• Change in 24 Hour Energy Expenditure

  Baseline and 14 days

• Change in Cumulative Fat Imbalance

  Baseline and 14 days

• Caudate Dopamine D2-like Receptor Binding Potential (D2BP)

  Day 2 of in-patient admission

• Putamen Dopamine D2-like Receptor Binding Potential (D2BP)

  Day 2 of in-patient admission

• Accumbens Dopamine D2-like Receptor Binding Potential (D2BP)

  Day 2 of in-patient admission

Study Arms (3)

Obese RF then RC

EXPERIMENTAL

Obese adult volunteers (BMI above 30 kg/m2) randomized to receive an 85% reduction of baseline dietary fat (RF) for 2 weeks. After a washout period of 2 weeks, they then received a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks

Other: Reduced fat diet; Other: Reduced carbohydrate diet; Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET

Obese RC then RF

EXPERIMENTAL

Obese adult volunteers (BMI above 30 kg/m2) randomized to receive a 60% reduction of baseline dietary carbohydrate (RC) for 2 weeks. After a washout period of 2 weeks, they then received an 85% reduction of baseline dietary fat (RF) for 2 weeks.

Other: Reduced fat diet; Other: Reduced carbohydrate diet; Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET

Lean Control

ACTIVE COMPARATOR

Lean adult volunteers (BMI below 30kg/m2) placed on a weight-maintenance diet using a standard diet composition of 50% carbohydrate, 35% fat, and 15% protein on an out-patient basis

Drug: Drug: f-18 fallypride; Device: fMRI; Device: PET

Interventions

Reduced fat diet OTHER

RF (selective reduction of 85% of baseline fat calories per day)

Obese RC then RF; Obese RF then RC

Reduced carbohydrate diet OTHER

RC (selective reduction of 60% of baseline carbohydrate calories per day)

Obese RC then RF; Obese RF then RC

Drug: f-18 fallypride DRUG

Dopamine D2 receptor availability is measured by positron emission tomography (PET) using the positron emitting compound \[18F\] fallypride which binds competitively with dopamine to the D2 receptor.

Lean Control; Obese RC then RF; Obese RF then RC

fMRI DEVICE

Functional MRI (fMRI) will be used to measure the effects of diet and weight loss on regional brain activity

Also known as: Functional MRI

Lean Control; Obese RC then RF; Obese RF then RC

PET DEVICE

Positron emission tomography (PET) will be used to assess whether To assess whether brain activity and reward pathways are altered

Also known as: Positron emission tomography

Lean Control; Obese RC then RF; Obese RF then RC

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-45 years, male or female
• Body mass less than 350 lbs. (max. weight dictated by table limit for functional magnetic resonance imaging (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 greater than or equal to 30.0 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

You may not qualify if:

• 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 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.).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (8)

• 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. doi: 10.1001/jama.282.16.1523.

  PMID: 10546691 BACKGROUND

• 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. doi: 10.2105/ajph.89.8.1194.

  PMID: 10432905 BACKGROUND

• 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. doi: 10.1056/NEJMoa022637.

  PMID: 12761364 BACKGROUND

• Hall KD, Bemis T, Brychta R, Chen KY, Courville A, Crayner EJ, Goodwin S, Guo J, Howard L, Knuth ND, Miller BV 3rd, Prado CM, Siervo M, Skarulis MC, Walter M, Walter PJ, Yannai L. Calorie for Calorie, Dietary Fat Restriction Results in More Body Fat Loss than Carbohydrate Restriction in People with Obesity. Cell Metab. 2015 Sep 1;22(3):427-36. doi: 10.1016/j.cmet.2015.07.021. Epub 2015 Aug 13.

  PMID: 26278052 RESULT

• Guo J, Simmons WK, Herscovitch P, Martin A, Hall KD. Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior. Mol Psychiatry. 2014 Oct;19(10):1078-84. doi: 10.1038/mp.2014.102. Epub 2014 Sep 9.

  PMID: 25199919 RESULT

• Simmons WK, Rapuano KM, Ingeholm JE, Avery J, Kallman S, Hall KD, Martin A. The ventral pallidum and orbitofrontal cortex support food pleasantness inferences. Brain Struct Funct. 2014 Mar;219(2):473-83. doi: 10.1007/s00429-013-0511-0. Epub 2013 Feb 9.

  PMID: 23397317 RESULT

• Simmons WK, Rapuano KM, Kallman SJ, Ingeholm JE, Miller B, Gotts SJ, Avery JA, Hall KD, Martin A. Category-specific integration of homeostatic signals in caudal but not rostral human insula. Nat Neurosci. 2013 Nov;16(11):1551-2. doi: 10.1038/nn.3535. Epub 2013 Sep 29.

  PMID: 24077565 RESULT

• Darcey VL, Guo J, Courville AB, Gallagher I, Avery JA, Simmons WK, Ingeholm JE, Herscovitch P, Martin A, Hall KD. Dietary fat restriction affects brain reward regions in a randomized crossover trial. JCI Insight. 2023 Jun 22;8(12):e169759. doi: 10.1172/jci.insight.169759.

  PMID: 37345661 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Obesity; Weight Loss; Platelet Glycoprotein IV Deficiency

Interventions

Magnetic Resonance Imaging; Positron-Emission Tomography

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Tomography, Emission-Computed; Image Interpretation, Computer-Assisted; Image Enhancement; Photography; Radionuclide Imaging; Diagnostic Techniques, Radioisotope

Results Point of Contact

• Title: Kevin Hall, PhD
• Organization: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

kevinh@niddk.nih.gov

3014028248

Study Officials

• Kevin Hall, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 14, 2009
• First Posted: February 18, 2009
• Study Start: February 13, 2009
• Primary Completion: February 24, 2014
• Study Completion: October 20, 2014
• Last Updated: April 15, 2021
• Results First Posted: March 24, 2021

Record last verified: 2020-01-22

Locations

US (1)