An observational study in Obesity, sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Completed at 1 site in United States. Open to participants aged 18 Years to 55 Years. Per ClinicalTrials.gov, last updated 2026-08-24.
Sponsored by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) · Observational
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:
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.
Some people appear to be more resistant than others to gaining weight when they overeat, though they do not increase their physical activity. This may indicate that adaptive mechanisms exist, which lead to wasting as heat part of the excess calories taken in. Such mechanisms exist in rodents including activation of brown fat, a tissue which can also convert calories to heat for warmth. Human studies have provided conflicting results. A pilot study on the relationship of the weight change over time with the changes in the amount of energy an individual uses over 24 hours (energy expenditure, EE) with 48-h overfeeding (OF) and fasting (F) in Pima Indian men has shown that persons with the greatest increase in EE with OF and the smallest decrease in EE with F gained the least weight over time, indicating that the ability to waste more calories when overfed may reduce weight gain. Other studies, however, have not shown this relationship. In addition, it has been proposed that unbalanced diets can help magnify these effects. The aims of this study are to test whether (a) the changes in EE in response to 24-h OF and F predict changes in weight over two years, and (b) high-carbohydrate diets or diets with high or low protein amounts may magnify the metabolic response to 24-h OF compared to normal protein and high-fat diets. 86 volunteers will be evaluated at baseline, 6 months and on a yearly basis for up to 7 years. At baseline, subjects will undergo 8 24-h sessions in a human respiratory chamber to measure EE while on a weight-maintaining diet, and then in random order: fasting, 200% OF on a normal-protein diet, 200% OF on a high fat, low-protein diet, 200% OF on a high-fat, normal-protein diet, 200% OF on a high fat, high protein diet, and 200% OF on a high-carbohydrate, normal-protein diet. Fifteen volunteers will have two additional chambers to try and understand if the source of carbohydrates, i.e. simple sugars versus complex carbohydrates, in a high carbohydrate diet affect metabolism. Thirty volunteers are planned to also undergo 2 positron emission tomography (PET) studies to look at the relationship of brown fat with EE in adult humans. (As of April 2021, we will stop performing the PET scans; 24 volunteers have completed them and we have acquired sufficient data.) Body weight and composition will be measured at each subsequent admission. Hormonal measurements to find determinants of adaptive changes in EE in response to OF and F will also be performed. This study will provide significant insights into possible mechanisms that may help people resist weight gain and obesity.
Residents of the Phoenix metropolitan area
Exclusion Criteria
Prior to beginning any of the study procedures, all subjects will be fully informed of the aim, nature, and risks of the study prior to giving written informed consent. The study s informed consent will be obtained by a principal or associate investigator, research physician or physician assistant working in the clinical research unit.
Healthy volunteers with normal glucose regulation
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
Time frame: 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
Time frame: 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
Time frame: 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, FDG-PET and FDG-CT scans, core body and distal skin temperature
Changes in BAT levels in response to cool temperature (16 degrees C), changes in energy expenditure, or changes in diet
Time frame: 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
Predictive value of substrate oxidation in chambers for changes in appetite sensations upon completion of 24 hour respiratory chamber
Time frame: 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
Repeatability of changes in energy expenditure in response to overfeeding and fasting diets with high, normal, or low levels of carbohydrates, protein, or fat
Time frame: 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
Effect of simple sugars and complex carbohydrates during overfeeding on energy expenditure
Time frame: 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 response to overfeeding in response to thermal insulation of the body core
Time frame: at baseline visit, 6 month visit, and then annually for up to 7 years
Hormone values in blood and urine,
Changes in hormones involved in the regulation of energy metabolism in response to overfeeding and fasting diets with high, normal, or low levels of carbohydrates, protein, or fat
Time frame: at baseline visit, 6 month visit, and then annually for up to 7 years
Core body and distal skin temperature
Changes in thermic effect of food during overfeeding in response to beta blockade
Time frame: at baseline visit, 6 month visit, and then annually for up to 7 years
Plan to share: Undecided
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)