Predicting Weight Gain and Weight Loss Associated With Overeating or Fasting

NCT00687115 | Completed Phase 2

• 2 other identifiers: 99990814008-DK-N140
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

This study will investigate how to better predict why some individuals gain or lose weight more easily than others. It will examine whether the increase in the amount of energy a body burns in 24 hours with overeating or the decrease over 24 hours with fasting can help determine how easily someone gains or loses weight. Healthy people between 18 and 60 years of age who have a body mass index (BMI) between 18.5 kg/m(2) and 24 kg/m(2) (for overfeeding study) or a BMI greater than 27 kg/m(2) with a body weight less than 350 pounds (weight loss study) may be eligible for this study. The study requires a 10-week admission to the NIH Clinical Center (2-week baseline, 6-week overfeeding/weight loss, 2-week post-weight change). Participants undergo the following tests and procedures during the hospital admission:

• Medical history, physical examination and laboratory studies
• Questionnaires to assess eating behavior, food preferences, body composition, and activity level
• Body composition assessment (height, weight, waist circumference, and fat mass and muscle content through DXA and MRI scans)
• Oral glucose tolerance test
• Meal test to measure the response of certain hormones to food
• Activity monitors to determine activity level
• Metabolic chamber study to measure calories burned over 24 hours and monitor body temperature
• Free-living energy use study to measure calories burned under normal home conditions over 7 days
• Fat and muscle biopsies
• Dietary intervention: Measurements of food intake and energy loss over a 6-week overfeeding (1.5 times the subject s normal food intake) or weight loss (one-half the subject s normal food intake) program Followup procedures after the inpatient stay:
• Height and weight measurements at 6 months (overfeeding study participants) and monthly for the first year, at 3-month intervals for the second year, and then yearly for 3 more years (weight loss study participants)
• Yearly visits (2-night inpatient stay) for all participants for repeat meal test, DXA, oral glucose tolerance test, behavioral questionnaires and, in women who can become pregnant, pregnancy test

Conditions

Diet Therapy; Weight Gain; Nutrition Therapy; Obesity; Weight Loss

Keywords

24 Hour Energy Expenditure; Respiratory Chamber; Obesity; Weight Loss; Overfeeding

Outcome Measures

Primary Outcomes (1)

• The primary goal of the current study is to determine if changes in energy expenditure in response to acute over- and underfeeding are related to variation in changes in weight and body energy stores with longer-term over- and underfeeding.

  Changes in energy expenditure, weight, and body energy stores measured via physical examinations, laboratory studies, questionnaires, body composition assessments, oral glucose tolerance tests, metabolic chamber studies, and free-living energy use studies

  Ongoing

Secondary Outcomes (1)

• Determine if hormones, responses to behavioral testing, adipocyte size, body composition, core temperature, spontaneous activity, and food absorption/excretion are related to changes in EE with over/under-feeding and variation in weight change.

  Ongoing

Study Arms (2)

Overfeeding

OTHER

an inpatient overfeeding arm in which obesity resistant individuals are prescribed a 150% increase in a weight maintenance calorie diet for 6 weeks which (by random assignment) is either low in protein (6%) content. Overfeeding or Overfeeding Low Pro or with normal (20%) protein content

Behavioral: Overfeeding; Behavioral: Overfeeding Low Pro

Weight Loss

OTHER

a weight loss arm in which obese individuals are placed on a 50% decrease from a weight maintenance calorie diet for 6 weeks which (by random assignment) is either a standard 50% decrease in energy intake with all macronutrients held at the same percentage (20% protein, 50% carbohydrate, 30% fat) or a 50% decrease in energy intake with the same absolute protein content (in grams) as the weight maintaining diet while on our clinical research unit then followed as outpatients monthly for 10 months

Behavioral: Weight Loss

Interventions

Weight Loss BEHAVIORAL

liquid diet at 50% of weight maintaining intake

Weight Loss

Overfeeding BEHAVIORAL

Overfeeding at 150% of weight maintaining intake

Overfeeding

Overfeeding Low Pro BEHAVIORAL

Overfeeding 150% of normal intake at \<5% protein

Overfeeding

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• BMI greater than or equal to 27 kg/m(2) for the weight loss protocol but body weight less than 350 pounds to accommodate the DXA scanner.
• BMI less than or equal to 24 kg/m(2) (and BMI greater than or equal to 18.5 kg/m(2) for the overfeeding protocols. A history of low BMI and difficulty gaining weight.
• Age 18-60 years, to minimize potential co-morbid conditions which may indirectly affect EE. Minors under the age of 18 will be excluded because growth and pubertal issues are significant parameters that could affect our outcomes and also because the time requirements of the study are such that they would interfere with school schedules. Women who are post-menopausal will be excluded from the study as changes in their metabolism could affect the baseline measurements which are hypothesized to predict weight change.
• Healthy, as determined by medical history, physical examination, and laboratory tests

You may not qualify if:

• Current smoking
• Type 2 diabetes (according to the World Health Organization diagnostic criteria)
• Impaired glucose tolerance (according to the World Health Organization diagnostic criteria) for those participating in the overfeeding study arms only
• Endocrine disorders (Cushing s Disease, pituitary disorders, and hypo- and hyperthyroidism)
• Chronic pulmonary disorders, including chronic obstructive pulmonary disease that would limit ability to follow the protocol (investigator judgment) and obstructive sleep apnea syndrome; only subjects with mild or exercise-induced asthma on no medications or on beta-adrenergic agonists only (such as albuterol) will be allowed to enter the study (provided use of these agents is not required for one week before study entry).
• Cardiovascular diseases (coronary heart disease, heart failure, arrhythmias, and peripheral artery disease)
• Hypertension (blood pressure measurement higher than 140/90 mm Hg (overfeeding study) or 160/95 (weight loss study) on two or more occasions or use of anti-hypertensive medications)
• Diagnosed gastrointestinal diseases, including inflammatory bowel diseases (e.g., Crohn s disease and ulcerative colitis), malabsorption syndromes (e.g., celiac disease), gastric ulcer (active); only subjects with gastro-esophageal reflux will be allowed to enter the study
• Presence of a pacemaker or other implantable devices/shrapnel which may interfere with the MRI or CorTemp measurements
• Liver disease (cirrhosis, active hepatitis B or C, and AST or ALT greater than or equal to 1.5 times normal)
• Renal disease (serum creatinine concentrations greater than or equal to 1.5 mg/dl and/or overt proteinuria)
• Central nervous system disease (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)
• Alcohol (more than 3 drinks per day) and/or drug abuse (such as amphetamines, cocaine, heroin, or marijuana)
• Current or past history of: bipolar disorder, schizophrenia or presence of psychotic symptoms, bulimia nervosa or anorexia nervosa, or current major depressive disorder

Sponsors & Collaborators

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

Study Sites (1)

NIDDK, Phoenix

Phoenix, Arizona, 85004, United States

Location

Related Publications (12)

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• Allison DB, Heshka S, Sepulveda D, Heymsfield SB. Counting calories--caveat emptor. JAMA. 1993 Sep 22-29;270(12):1454-6. doi: 10.1001/jama.270.12.1454.

  PMID: 8371446 BACKGROUND

• Astrup A, Buemann B, Christensen NJ, Madsen J, Gluud C, Bennett P, Svenstrup B. The contribution of body composition, substrates, and hormones to the variability in energy expenditure and substrate utilization in premenopausal women. J Clin Endocrinol Metab. 1992 Feb;74(2):279-86. doi: 10.1210/jcem.74.2.1530952.

  PMID: 1530952 BACKGROUND

• Cabeza de Baca T, Parrington S, Votruba S, Piaggi P, Krakoff J, Chang DC. Adipocyte size, adipose tissue calories, and circulating adipokines, before and after diet-induced weight loss in humans. Endocrine. 2024 May;84(2):490-499. doi: 10.1007/s12020-023-03666-3. Epub 2024 Jan 4.

  PMID: 38172345 DERIVED

• Basolo A, Parrington S, Ando T, Hollstein T, Piaggi P, Krakoff J. Procedures for Measuring Excreted and Ingested Calories to Assess Nutrient Absorption Using Bomb Calorimetry. Obesity (Silver Spring). 2020 Dec;28(12):2315-2322. doi: 10.1002/oby.22965. Epub 2020 Oct 7.

  PMID: 33029899 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

• Hollstein T, Ando T, Basolo A, Krakoff J, Votruba SB, Piaggi P. Metabolic response to fasting predicts weight gain during low-protein overfeeding in lean men: further evidence for spendthrift and thrifty metabolic phenotypes. Am J Clin Nutr. 2019 Sep 1;110(3):593-604. doi: 10.1093/ajcn/nqz062.

  PMID: 31172178 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

• 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

• Heinitz S, Piaggi P, Yang S, Bonfiglio S, Steel J, Krakoff J, Votruba SB. Response of skeletal muscle UCP2-expression during metabolic adaptation to caloric restriction. Int J Obes (Lond). 2018 Jun;42(5):974-984. doi: 10.1038/s41366-018-0085-2. Epub 2018 May 17.

  PMID: 29777235 DERIVED

• Reinhardt M, Thearle MS, Ibrahim M, Hohenadel MG, Bogardus C, Krakoff J, Votruba SB. A Human Thrifty Phenotype Associated With Less Weight Loss During Caloric Restriction. Diabetes. 2015 Aug;64(8):2859-67. doi: 10.2337/db14-1881. Epub 2015 May 11.

  PMID: 25964395 DERIVED

MeSH Terms

Conditions

Obesity; Weight Loss; Weight Gain

Condition Hierarchy (Ancestors)

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

Study Officials

• Susanne M Votruba, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 29, 2008
• First Posted: May 30, 2008
• Study Start: September 18, 2008
• Primary Completion: December 31, 2018
• Study Completion: March 20, 2023
• Last Updated: April 14, 2026

Record last verified: 2026-02-06

Locations

US (1)