Effects of Diet Changes on Metabolism

NCT00523627 | Completed

• 2 other identifiers: 99990721507-DK-N215
• Study Type: observational
• Target: 203
• Locations: 1 country
• Sites: 1

Brief Summary

This study, conducted at the NIH Clinical Research Unit at the Phoenix Indian Medical Center, will examine how the body s metabolism (energy expenditure) changes when people overeat and when they fast and how different diets (e.g., high-protein or high-fat) affect metabolism. The results may provide information about whether there are mechanisms that make some people more resistant than others to gaining weight when they eat more. Non-smoking healthy subjects between 18 and 55 years of age who weigh no more than 350 pounds may be eligible for this study. Participants undergo the following procedures:

• Pregnancy test for women of childbearing age.
• Oral glucose tolerance test. For this test, an I.V. line (needle attached to a plastic tube) is inserted into a vein to allow several blood draws without repeated needle sticks. After the first blood sample is drawn, the subject drinks a cola-flavored sugar solution. Five additional blood samples are then drawn over 3 hours.
• Blood test for DNA (genetic) studies related to obesity, diabetes and related medical problems.
• DEXA scan. This test measures body fat. The subject lies on a table while a very small dose of X-rays is passed through the body.
• Respiratory chamber. This test measures how many calories the body burns a day and assesses energy balance between intake and expenditure. Subjects stay in a room with two windows, equipped with a sink, toilet, television and DVD player, desk, chair, telephone and bed for 24 hours. The test is repeated five times during the first 18-day admission and 3 times during the second 13-day admission. For the first two sessions, subjects are fed a diet equal to the amount of energy their body uses. For the next 6 stays they are fed double the amount of calories their body usually uses for 5 of the stays and fast (consume nothing but water and soda without caffeine or calories) during 1 stay. The overfeeding diets may be high or low in protein, normal in protein, or high in fat. Blood tests are done on the day of each respiratory chamber session and a 24-hour urine sample is collected for one day while in the chamber.
• Eating behavior questionnaires.
• Psychological performance tests. Some participants are asked to volunteer to repeat two of the chamber studies to validate the measurements. The repeat session includes only the fasting and the overfeeding with normal protein content. All participants are followed at 6 months with blood tests, a DEXA scan, and urine tests (including pregnancy test for women). At annual visits for years 1 through 7, participants have the 6-month tests plus an oral glucose tolerance test.

Conditions

Obesity

Keywords

Energy Expenditure; Adaptive Thermogenesis; Low-protein Overfeeding; Fasting; Weight Gain; Natural History

Outcome Measures

Primary Outcomes (3)

• Weight, DXA scans, resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature

  Changes in body weight and composition in response to changes in energy expenditure

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Weight, DXA scans

  Changes in body weight and composition in response to overfeeding and fasting diets with high, normal, or low levels of carbohydrates, protein, or fat

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature

  Changes in energy expenditure in response to overfeeding and fasting diets with high, normal, or low levels of carbohydrates, protein, or fat

  at baseline visit, 6 month visit, and then annually for up to 7 years

Secondary Outcomes (7)

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, FDG-PET and FDG-CT scans, core body and distal skin temperature

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature, questionnaires

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature

  at baseline visit, 6 month visit, and then annually for up to 7 years

• Resting metabolic rate, thermic effect of food, energy cost of physical activity, cycle ergometry, core body and distal skin temperature

  at baseline visit, 6 month visit, and then annually for up to 7 years

Study Arms (1)

Healthy Volunteers with normal glucose regulation

Healthy volunteers with normal glucose regulation

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Probability Sample

Study Population

Residents of the Phoenix metropolitan area

You may qualify if:

• Age: 18-55 years, to exclude effects of aging on energy expenditure and weight change. For the PET-CT substudy, women will be limited to ages 18-40 years because there is a high likelihood that for women greater than 40 years, their personal physician may recommend an annual routine mammogram, thereby increasing their annual radiation exposure. Men will also be limited to this age range to prevent age discrepancies between men and women for this substudy.
• Premenopausal
• Weight: less than or equal to 450 lb (maximum weight allowed on the DXA scanning tables by the manufacturer).

You may not qualify if:

• History or clinical manifestation of:
• Current smoking
• Impaired glucose tolerance (IGT), type 1 and type 2 diabetes
• Endocrine disorders, such as Cushing s disease, pituitary disorders, and hypo- and hyperthyroidism
• Pulmonary disorders, including chronic obstructive pulmonary disease, which would limit ability to follow the protocol (investigator judgment)
• Cardiovascular diseases, including coronary heart disease, heart failure, arrhythmias, and peripheral artery disease
• Hypertension, as diagnosed and treated by an outside physician or by sitting blood pressure measurement, using an appropriate cuff, higher than 140/90 mmHg on two or more occasions
• Liver disease, including cirrhosis, active hepatitis B or C, and AST or ALT greater than or equal to 3 times normal
• Renal disease, as defined by serum creatinine concentrations greater than or equal 1.5 mg/dl and/or proteinuria greater than 300 mg/day (200 (Micro)g/min)
• Central nervous system disease, including previous history of cerebrovascular accidents, dementia, and neurodegenerative disorders
• Cancer requiring treatment in the past five years, except for non-melanoma skin cancers or cancers that have clearly been cured or in the opinion of the investigator carry an excellent prognosis (e.g., Stage 1 cervical cancer).
• Infectious disease such as active tuberculosis, HIV (by self-report), chronic coccidiomycoses or other chronic infections that might influence weight.
• Alcohol and/or drug abuse (more than 3 drinks per day and use of drugs, such as amphetamines, cocaine, heroin, or marijuana).
• Pregnancy or lactation
• For the PET-CT substudy, radiation exposure to the torso for research or medical purposes within the past 12 months

Sponsors & Collaborators

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

Study Sites (1)

NIDDK, Phoenix

Phoenix, Arizona, 85014, United States

Location

Related Publications (17)

• Trevino-Alvarez AM, Cabeza de Baca T, Stinson EJ, Gluck ME, Chang DC, Piaggi P, Krakoff J. Greater anhedonia scores in healthy individuals are associated with less decline in 24-hour energy expenditure with fasting: Evidence for a link between behavioral traits and spendthrift phenotype. Physiol Behav. 2023 Oct 1;269:114281. doi: 10.1016/j.physbeh.2023.114281. Epub 2023 Jun 24.

  PMID: 37356515 DERIVED

• Hollstein T, Basolo A, Unlu Y, Ando T, Walter M, Krakoff J, Piaggi P. Effects of Short-term Fasting on Ghrelin/GH/IGF-1 Axis in Healthy Humans: The Role of Ghrelin in the Thrifty Phenotype. J Clin Endocrinol Metab. 2022 Aug 18;107(9):e3769-e3780. doi: 10.1210/clinem/dgac353.

  PMID: 35678263 DERIVED

• Hollstein T, Basolo A, Ando T, Krakoff J, Piaggi P. Reduced adaptive thermogenesis during acute protein-imbalanced overfeeding is a metabolic hallmark of the human thrifty phenotype. Am J Clin Nutr. 2021 Oct 4;114(4):1396-1407. doi: 10.1093/ajcn/nqab209.

  PMID: 34225360 DERIVED

• Hollstein T, Basolo A, Ando T, Votruba SB, Walter M, Krakoff J, Piaggi P. Recharacterizing the Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes. J Clin Endocrinol Metab. 2020 May 1;105(5):1375-92. doi: 10.1210/clinem/dgaa098.

  PMID: 32118268 DERIVED

• Hollstein T, Basolo A, Ando T, Votruba SB, Krakoff J, Piaggi P. Urinary Norepinephrine Is a Metabolic Determinant of 24-Hour Energy Expenditure and Sleeping Metabolic Rate in Adult Humans. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1145-56. doi: 10.1210/clinem/dgaa047.

  PMID: 32002540 DERIVED

• Begaye B, Vinales KL, Hollstein T, Ando T, Walter M, Bogardus C, Krakoff J, Piaggi P. Impaired Metabolic Flexibility to High-Fat Overfeeding Predicts Future Weight Gain in Healthy Adults. Diabetes. 2020 Feb;69(2):181-192. doi: 10.2337/db19-0719. Epub 2019 Nov 11.

  PMID: 31712321 DERIVED

• Piaggi P. Metabolic Determinants of Weight Gain in Humans. Obesity (Silver Spring). 2019 May;27(5):691-699. doi: 10.1002/oby.22456.

  PMID: 31012296 DERIVED

• Vinales KL, Begaye B, Thearle MS, Krakoff J, Piaggi P. Core body temperature, energy expenditure, and epinephrine during fasting, eucaloric feeding, and overfeeding in healthy adult men: evidence for a ceiling effect for human thermogenic response to diet. Metabolism. 2019 May;94:59-68. doi: 10.1016/j.metabol.2019.01.016. Epub 2019 Jan 31.

  PMID: 30710573 DERIVED

• Stinson EJ, Graham AL, Thearle MS, Gluck ME, Krakoff J, Piaggi P. Cognitive dietary restraint, disinhibition, and hunger are associated with 24-h energy expenditure. Int J Obes (Lond). 2019 Jul;43(7):1456-1465. doi: 10.1038/s41366-018-0305-9. Epub 2019 Jan 16.

  PMID: 30651576 DERIVED

• Begaye B, Piaggi P, Thearle MS, Haskie K, Walter M, Schlogl M, Bonfiglio S, Krakoff J, Vinales KL. Norepinephrine and T4 Are Predictors of Fat Mass Gain in Humans With Cold-Induced Brown Adipose Tissue Activation. J Clin Endocrinol Metab. 2018 Jul 1;103(7):2689-2697. doi: 10.1210/jc.2018-00387.

  PMID: 29788444 DERIVED

• Stinson EJ, Krakoff J, Gluck ME. Depressive symptoms and poorer performance on the Stroop Task are associated with weight gain. Physiol Behav. 2018 Mar 15;186:25-30. doi: 10.1016/j.physbeh.2018.01.005. Epub 2018 Jan 9.

  PMID: 29326031 DERIVED

• Vinales KL, Schlogl M, Reinhardt M, Thearle MS, Krakoff J, Piaggi P. Cycling Efficiency During Incremental Cycle Ergometry After 24 Hours of Overfeeding or Fasting. Obesity (Silver Spring). 2018 Feb;26(2):368-377. doi: 10.1002/oby.22096. Epub 2017 Dec 25.

  PMID: 29276860 DERIVED

• Ibrahim M, Bonfiglio S, Schlogl M, Vinales KL, Piaggi P, Venti C, Walter M, Krakoff J, Thearle MS. Energy Expenditure and Hormone Responses in Humans After Overeating High-Fructose Corn Syrup Versus Whole-Wheat Foods. Obesity (Silver Spring). 2018 Jan;26(1):141-149. doi: 10.1002/oby.22068. Epub 2017 Nov 28.

  PMID: 29193741 DERIVED

• Vinales KL, Schlogl M, Piaggi P, Hohenadel M, Graham A, Bonfiglio S, Krakoff J, Thearle MS. The Consistency in Macronutrient Oxidation and the Role for Epinephrine in the Response to Fasting and Overfeeding. J Clin Endocrinol Metab. 2017 Jan 1;102(1):279-289. doi: 10.1210/jc.2016-3006.

  PMID: 27820654 DERIVED

• Ibrahim M, Thearle MS, Krakoff J, Gluck ME. Perceived stress and anhedonia predict short-and long-term weight change, respectively, in healthy adults. Eat Behav. 2016 Apr;21:214-9. doi: 10.1016/j.eatbeh.2016.03.009. Epub 2016 Mar 3.

  PMID: 27002703 DERIVED

• Schlogl M, Piaggi P, Thiyyagura P, Reiman EM, Chen K, Lutrin C, Krakoff J, Thearle MS. Overfeeding over 24 hours does not activate brown adipose tissue in humans. J Clin Endocrinol Metab. 2013 Dec;98(12):E1956-60. doi: 10.1210/jc.2013-2387. Epub 2013 Sep 30.

  PMID: 24081739 DERIVED

• Thearle MS, Pannacciulli N, Bonfiglio S, Pacak K, Krakoff J. Extent and determinants of thermogenic responses to 24 hours of fasting, energy balance, and five different overfeeding diets in humans. J Clin Endocrinol Metab. 2013 Jul;98(7):2791-9. doi: 10.1210/jc.2013-1289. Epub 2013 May 10.

  PMID: 23666976 DERIVED

MeSH Terms

Conditions

Obesity; Fasting; Weight Gain

Condition Hierarchy (Ancestors)

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

Study Officials

• Tomas Cabeza De Baca, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2007
• First Posted: August 31, 2007
• Study Start: May 22, 2008
• Last Updated: June 5, 2026

Record last verified: 2026-02-06

Locations

US (1)