ObesityPhase 2NCT00687115
Predicting Weight Gain and Weight Loss Associated With Overeating or Fasting
A Phase 2 study testing Weight Loss, Overfeeding and Overfeeding Low Pro in people with Obesity and Diet Therapy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Obesity, Diet Therapy, Weight Loss
- What is being tested?
- Weight Loss, Overfeeding and Overfeeding Low Pro
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Sep 2008to 20 Mar 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 19Show fewer
- 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
- Pregnancy or lactation
- Taking weight loss medications
- Weight change of plus or minus 5% in the last 3 months
- Conditions not specifically mentioned above may serve as criteria for exclusion at the discretion of the investigators. Additionally, potential subjects might be excluded if they demonstrate a style of interpersonal relationships that would inhibit successful completion of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Predicting Adaptive Thermogenesis
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).
Read more
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
Read the detailed description
For obese individuals, losing weight and keeping it off are extremely difficult, whereas some other individuals are thin and report trouble gaining weight. In most weight loss and overfeeding studies there is a large variation in the amount of weight lost or gained, and it is not clear whether an individual s response to an intervention can be predicted. Measurement of the amount of energy an individual uses over 24 hours (24 hour energy expenditure or 24-EE) and the response of 24-EE to overfeeding and fasting may help predict which individuals will have the greatest changes in weight with changes in energy balance. In previous work, 24-EE responses to overfeeding and fasting were related such that individuals with the greatest increase in 24-EE upon overfeeding tended to have the smallest decrease in 24-EE upon fasting ( spendthrift phenotype) and those individuals with less increase in 24-EE during overfeeding had a greater decrease in 24-EE with fasting ( thrifty phenotype). Those with the spendthrift phenotype who had a greater increase in 24-EE in response to overfeeding gained less weight over time. Furthermore, studies have shown that diets with very low protein content may magnify the variability in response to overfeeding.
The aim of this study is to determine if a phenotype defined by 24-EE responses to overfeeding and underfeeding is related to weight loss or gain in 4 different under- and overfeeding settings: an inpatient weight loss group for obese individuals who will be administered one of two diets based on a 50% reduction of their daily energy needs for six weeks (standard reduction diet or calorie reduced diet that is still high in protein; 6 week weight reduction, 10 week stay, n=20/standard reduction diet group and n=10/relative high protein diet), and two overfeeding groups for lean, weight gain resistant individuals: a low-protein overfeeding group at 150% of daily energy needs for 6 weeks overfeeding (6% protein, 64% carbohydrate, 30% fat; 10 week stay, n=10), and a normal protein overfeeding group at 150% of daily energy needs for 6 weeks overfeeding (20% protein, 50% carbohydrate, 30% fat; 10 week stay, n=10). We will also examine additional metabolic and behavioral measurements to determine how they relate to weight change and changes in 24-EE. These include sympathetic nervous system activity, behavior, adipose and muscle tissue energy content, and abdominal adipocyte size. The study will evaluate the relationship between the percent increase in 24-EE in response to overfeeding/underfeeding and the amount of weight change over time in each subject. These findings may provide important information for predicting and adapting specific individualized interventions for obesity.
- Conditions
- Obesity, Diet Therapy, Weight Loss, Weight Gain, Nutrition Therapy
- Being tested
- Weight Loss, Overfeeding, Overfeeding Low Pro
- Keywords
- 24 Hour Energy Expenditure, Respiratory Chamber, Obesity, Weight Loss, Overfeeding
- Medical subject headings
- Obesity, Weight Loss, Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Weight LossBehavioural
liquid diet at 50% of weight maintaining intake
OverfeedingBehavioural
Overfeeding at 150% of weight maintaining intake
Overfeeding Low ProBehavioural
Overfeeding 150% of normal intake at <5% protein
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: Behavioral: Weight Loss |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Changes in hormones, behavior, adipocyte size, body composition, core temperature, spontaneous activity, food absorption/excretion, changes in EE, and weight measured via physical examinations, laboratory studies, questionnaires, body composition assessments, oral glucose tolerance tests, meal tests, activity monitors, metabolic chamber studies, free-living energy use studies, and fat and muscle biopsies
Measured: Ongoing
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2008 (estimated)
- Study start18 Sep 2008
- Primary completion31 Dec 2018
- Study completion20 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 83 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Susanne M Votruba, Ph.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00687115
- Sponsor's protocol ID
- 999908140
- Other IDs
- 08-DK-N140
- Status last verified
- 17 Jul 2026
- First submitted
- 29 May 2008
- Last updated
- 26 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, Digby JE, Sewter CP, Lazar MA, Chatterjee VK, O'Rahilly S. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest. 1997 Dec 15;100(12):3149-53. doi: 10.1172/JCI119870.
PubMed 9399962Allison 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.
PubMed 8371446Astrup 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.
PubMed 1530952Cabeza 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.
PubMed 38172345Basolo 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.
PubMed 33029899Hollstein 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.
PubMed 32118268Hollstein 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.
PubMed 32002540Hollstein 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.
PubMed 31172178Piaggi P. Metabolic Determinants of Weight Gain in Humans. Obesity (Silver Spring). 2019 May;27(5):691-699. doi: 10.1002/oby.22456.
PubMed 31012296Stinson 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.
PubMed 30651576Heinitz 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.
PubMed 29777235Reinhardt 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.
PubMed 25964395
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predicting Adaptive Thermogenesis
- ClinicalTrials.gov ID
- NCT00687115
- Acronym / sponsor ID
- 999908140
- Conditions
- Obesity, Diet Therapy, Weight Loss, Weight Gain, Nutrition Therapy
- Keywords
- 24 Hour Energy Expenditure, Respiratory Chamber, Obesity, Weight Loss, Overfeeding
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 83 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 18 Sep 2008 (actual)
- Primary completion
- 31 Dec 2018 (actual)
- Study completion
- 20 Mar 2023 (actual)
- First posted
- 30 May 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
For obese individuals, losing weight and keeping it off are extremely difficult, whereas some other individuals are thin and report trouble gaining weight. In most weight loss and overfeeding studies there is a large variation in the amount of weight lost or gained, and it is not clear whether an individual s response to an intervention can be predicted. Measurement of the amount of energy an individual uses over 24 hours (24 hour energy expenditure or 24-EE) and the response of 24-EE to overfeeding and fasting may help predict which individuals will have the greatest changes in weight with changes in energy balance. In previous work, 24-EE responses to overfeeding and fasting were related such that individuals with the greatest increase in 24-EE upon overfeeding tended to have the smallest decrease in 24-EE upon fasting ( spendthrift phenotype) and those individuals with less increase in 24-EE during overfeeding had a greater decrease in 24-EE with fasting ( thrifty phenotype). Those with the spendthrift phenotype who had a greater increase in 24-EE in response to overfeeding gained less weight over time. Furthermore, studies have shown that diets with very low protein content may magnify the variability in response to overfeeding.
The aim of this study is to determine if a phenotype defined by 24-EE responses to overfeeding and underfeeding is related to weight loss or gain in 4 different under- and overfeeding settings: an inpatient weight loss group for obese individuals who will be administered one of two diets based on a 50% reduction of their daily energy needs for six weeks (standard reduction diet or calorie reduced diet that is still high in protein; 6 week weight reduction, 10 week stay, n=20/standard reduction diet group and n=10/relative high protein diet), and two overfeeding groups for lean, weight gain resistant individuals: a low-protein overfeeding group at 150% of daily energy needs for 6 weeks overfeeding (6% protein, 64% carbohydrate, 30% fat; 10 week stay, n=10), and a normal protein overfeeding group at 150% of daily energy needs for 6 weeks overfeeding (20% protein, 50% carbohydrate, 30% fat; 10 week stay, n=10). We will also examine additional metabolic and behavioral measurements to determine how they relate to weight change and changes in 24-EE. These include sympathetic nervous system activity, behavior, adipose and muscle tissue energy content, and abdominal adipocyte size. The study will evaluate the relationship between the percent increase in 24-EE in response to overfeeding/underfeeding and the amount of weight change over time in each subject. These findings may provide important information for predicting and adapting specific individualized interventions for obesity.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Overfeeding | Other | Behavioral: Overfeeding, Behavioral: Overfeeding Low Proan 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 |
| Weight Loss | Other | Behavioral: Weight Lossa 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 |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (19 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Weight Lossliquid diet at 50% of weight maintaining intake | Behavioural | Weight Loss |
| OverfeedingOverfeeding at 150% of weight maintaining intake | Behavioural | Overfeeding |
| Overfeeding Low ProOverfeeding 150% of normal intake at <5% protein | Behavioural | Overfeeding |
Primary outcome
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.
Time frame: Ongoing
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
1 secondary outcome
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.
Time frame: Ongoing
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Background: PubMed 9399962Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, Digby JE, Sewter CP, Lazar MA, Chatterjee VK, O'Rahilly S. Activators of peroxisome proliferator-activated receptor gamma have depot-specific effects on human preadipocyte differentiation. J Clin Invest. 1997 Dec 15;100(12):3149-53. doi: 10.1172/JCI119870.
- Background: PubMed 8371446Allison 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.
- Background: PubMed 1530952Astrup 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.
- Derived from this study: PubMed 38172345Cabeza 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.
- Derived from this study: PubMed 33029899Basolo 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.
- Derived from this study: PubMed 32118268Hollstein 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.
- Derived from this study: PubMed 32002540Hollstein 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.
- Derived from this study: PubMed 31172178Hollstein 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.
- Derived from this study: PubMed 31012296Piaggi P. Metabolic Determinants of Weight Gain in Humans. Obesity (Silver Spring). 2019 May;27(5):691-699. doi: 10.1002/oby.22456.
- Derived from this study: PubMed 30651576Stinson 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.
- Derived from this study: PubMed 29777235Heinitz 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.
- Derived from this study: PubMed 25964395Reinhardt 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.
- Individual participant dataSharing planned: Undecided
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Effects of Sequential Therapy With Mexidol® (Intravenous) and Mexidol® FORTE 250 (Oral) on Functional Brain Activity Assessed by Functional Magnetic Resonance Imaging and Biochemical Parameters in Patients With Chronic Cerebral Ischemia: A Comparison of Patients With and Without Metabolic Disorders
Metabolic Abnormalities, Obesity & Overweight
Recruiting
Exercise Training and Vitamin D Metabolism
Obesity & Overweight, Vitamin D
Recruiting
Metabolic Health, Bones and Nuts During Weight Loss in Adults
Weight Loss, Bone Density
Active, not recruiting
Effect of Probiotics on Insulin Sensitivity in Overweight and Obese Pregnancy
Obesity & Overweight, Gestational Diabetes Mellitus (GDM)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Susanne M Votruba, Ph.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Weight Loss, Overfeeding and Overfeeding Low Pro in people with Obesity and Diet Therapy, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Ongoing). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00687115, which also lists 12 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.