Food Intake Response to Short-Term Modifications of Metabolism in Humans

Energy Intake Response to Short-Term Alterations of Energy Expenditure in Humans

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02939404

Enrollment

Registered

2016-10-20

Start date

2017-04-27

Completion date

2024-06-24

Last updated

2025-07-04

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Healthy Volunteers

Keywords

Energy Intake, Energy Expenditure, Eating Behavior, Cold Exposure, Natural History

Brief summary

One reason people gain weight is eating more calories from food than what they need for energy over 24 hours. Metabolism is the amount of energy a person uses over 24 hours. Researchers want to study the relationship between changes in metabolism and how much a person eats. Objectives: To see how much food a person eats when the body's temperature is cooled. To study how changes in metabolism may alter the amount of food a person eats. Eligibility: Healthy people ages 18-55. Design: Participants will stay at NIH for 20 days. During the first 4 days, participants will have: * Medical exam * Electrocardiogram * Blood and urine tests. One blood test includes drinking a sugar solution. * DXA body composition scan * Questions about foods they like, physical activity, and personal behavior * Exercise test on a stationary bicycle Participants will spend 24-hour periods in a metabolic chamber. The chamber will be at normal room temperature or cooler. Some times, participants will eat a diet that matches their daily needs (fixed or eucaloric). Other times, they can eat as much as they wish from a vending machine (ad libitum). Participants will have blood and urine collected. Participants will swallow an ingestible wireless sensor and wear a small data recorder device. On the second to last day, participants will stay in the metabolic chamber but only consume water and non-caffeinated sugar-free beverages. Participants will come back for 1-day visits at six months and one year from the first admission. They will have blood and urine tests, and a DXA scan. They will answer questions on physical activity and food habits.

Detailed description

More than 30% of adults are considered overweight. In general, lifestyle changes (diet and exercise) or current weight loss drugs only lead to about 5 to 10% weight loss. This may be because a person's energy expenditure, aka the number of calories the body uses, leads to hunger and may increase the amount of food a person eats. Cold exposure is known to increase metabolism but it may not lead to weight loss if appetite and the desire for food are also increased. The primary goal of this study is to evaluate whether changing energy expenditure by cool temperature exposure results in changes in food intake. This study will involve a stay on our clinical research unit where we will determine the energy requirements (at 24 degree C) of 68 healthy, adult volunteers without evidence of diabetes. Exposure to cool temperatures (19 degree C) will be used to increase the number of calories a person's body uses in a day. Participants will spend 24 hours in a room that measures energy expenditure while the temperature in the room is turned down, once with a fixed diet (eucaloric) and once with a buffet of food choices (ad libitum). After the fixed diet, volunteers will self-select how much food they wish to eat for one day from a vending machine. Volunteers will also spend one day fasting followed by a day self-selecting their food from the vending machine. Findings from this study will provide knowledge about a possible causal link between energy expenditure and eating behavior. This information may shed light on why many weight loss interventions that increase energy expenditure do not work as well as expected, and may eventually lead to new weight loss approaches and therapies.

Interventions

OTHERCold exposure

23.25 hours inside respiratory chamber with the temperature set to19°C

OTHERNormal temperature

23.25 hours inside respiratory chamber with the temperature set to 24°C

OTHERFixed diet

A diet that matches the participant's caloric needs

OTHERAd libitum diet

Participants can eat as much as they want

OTHERFasting

Participants do not eat for 12 hours before and 24 hours in chamber

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 55 Years

Healthy volunteers

Inclusion criteria

* INCLUSION CRITERIA: * Premenopausal women and men \<55 years of age * Body weight \<204 kg (\<450 pounds) and \>= 36 kg (\>= 80 pounds) * Stable weight (+/-5% within past 6 months) as determined by volunteer report * Healthy, as determined by medical history, physical examination, and laboratory tests

Exclusion criteria

* Age \<18 years * Weight greater than or equal to 204 kg (greater than or equal to 450 pounds, maximum weight of the iDXA machine as per manufacturer s manual), or weight \<36 kg (\<80 pounds, minimum weight allowed based on the NIH guidelines of blood drawing for research purposes) * Use of medications affecting metabolism and appetite in the last three months * Expresses unwillingness to consume all food given during the weight maintaining diet portions of the study (e.g., due to strict dietary restrictions including allergies or vegetarian or kosher diet) * Current use of tobacco products, marijuana, amphetamines, cocaine, or intravenous drug use * Current pregnancy, pregnancy within the past 6 months or lactation * History or clinical manifestation of: * Type 1 and Type 2 diabetes mellitus * History of surgery for the treatment of obesity * Endocrine disorders, such as Cushing s disease, pituitary disorders, and hypo and hyperthyroidism * Pulmonary disorders, including chronic obstructive pulmonary disease * Cardiovascular diseases, including coronary heart disease, heart failure, arrhythmias, and peripheral artery disease * High blood pressure by sitting blood pressure measurement using an appropriate cuff higher than 140/90 mmHg on two or more occasions, or current antihypertensive therapy * Liver disease, including cirrhosis, active hepatitis B or C, and AST or ALT greater than or equal to 2x normal * Gastrointestinal disease including Crohn s disease, ulcerative colitis, celiac disease or other malabsorptive disorders * Abnormal kidney function (eGFR \<60 mL/min/1.73m(2)) * Central nervous system disease, including previous history of cerebrovascular accidents, dementia, neurodegenerative disorders or history of severe head trauma * Cancer requiring treatment in the past five years, except for nonmelanoma skin cancers or cancers that have clearly been cured * Infectious disease such as active tuberculosis, HIV (by self report), chronic coccidiomycoses or other chronic infections that might influence EE and weight * Diagnosis of binge eating disorder, anorexia and major psychiatric disorders based upon the DSM-IV including depression, schizophrenia and psychosis, which may impact the ability of the participant to be in the respiratory chamber for 24 hour time periods * Chronic ethanol use (more than 3 drinks/day)

Design outcomes

Primary

Measure	Time frame	Description
24-hour Energy Expenditure (kcal)	Days 6 (Chamber at 24°C, fixed diet), 10(Chamber at 24°C, ad libitum diet), 14(Chamber at 19°C, fixed or ad libitum diet), 18(Chamber at 19°C, fixed or ad libitum diet), and 21(Chamber at 24°C, fasting)	Energy expenditure (EE) as measured during 24 hours in a whole-room calorimeter
24-hour Energy Intake (kcal)	Days 6 (Chamber at 24°C, fixed diet), 10(Chamber at 24°C, ad libitum diet), 14(Chamber at 19°C, fixed or ad libitum diet), 18(Chamber at 19°C, fixed or ad libitum diet), and 21(Chamber at 24°C, fasting)	Energy intake as measured during 24 hours in a whole-room calorimeter

Secondary

Measure	Time frame	Description
Secretin	Days 6 (Chamber at 24°C, fixed diet), 14(Chamber at 19°C, fixed diet) or 18(Chamber at 19°C, fixed diet), and 21(Chamber at 24°C, fasting)	Plasma secretin (ng/ml)
Ghrelin	Days 6 (Chamber at 24°C, fixed diet), 14(Chamber at 19°C, fixed diet) or 18(Chamber at 19°C, fixed diet), and 21(Chamber at 24°C, fasting)	Plasma grehlin (pg/ml)
FGF-21	Days 6 (Chamber at 24°C, fixed diet), 14(Chamber at 19°C, fixed diet) or 18(Chamber at 19°C, fixed diet), and 21(Chamber at 24°C, fasting)	Plasma FGF-21 (pg/ml)
24- Hour Respiratory Quotient (RQ)	Days 6 (Chamber at 24°C, fixed diet), 10(Chamber at 24°C, ad libitum diet), 14(Chamber at 19°C, fixed or ad libitum diet), 18(Chamber at 19°C, fixed or ad libitum diet), and 21(Chamber at 24°C, fasting)	RQ, an approximation for the ratio of carbohydrate-to-fat oxidation rates, is measured while in the chamber
Weight Change at 6 Months	6 months	Weight change from baseline to 6 months
Weight Change at 12 Months	12 months	Weight change from baseline to 12 months
Core Body Temperature (C)	Days 6 (Chamber at 24°C, fixed diet), 14(Chamber at 19°C, fixed diet) or 18(Chamber at 19°C, fixed diet), and 21(Chamber at 24°C, fasting)	Core body temperature measured in chamber
Leptin	Days 6 (Chamber at 24°C, fixed diet), 14(Chamber at 19°C, fixed diet) or 18(Chamber at 19°C, fixed diet), and 21(Chamber at 24°C, fasting)	Plasma leptin (ng/ml)

Countries

United States

Participant flow

Participants by arm

Arm	Count
Chamber at 19°C With Fixed Diet First Order of chambers will be Chamber at normal room temperature (24°C) with fixed eucaloric diet, Chamber at 24°C with ad libitum diet, Chamber at 19°C with fixed eucaloric diet, Chamber at 19°C with ad libitum diet, and Chamber at 24°C fasting. Normal room temperature: 23.25 hours inside respiratory chamber with the temperature set to 24°C Fixed diet: A diet that matches the participant's caloric needs Ad libitum diet: Participants can eat as much as they want (self-select how much food they wish to eat)	24
2. Chamber at 19°C, ad Libitum Diet First Order of chambers will be Chamber at normal room temperature (24°C) with fixed eucaloric diet, Chamber at 24°C with ad libitum diet, Chamber at 19°C with ad libitum diet, Chamber at 19°C with fixed eucaloric diet, and Chamber at 24°C fasting. Normal room temperature: 23.25 hours inside respiratory chamber with the temperature set to 24°C Fixed diet: A diet that matches the participant's caloric needs Ad libitum diet: Participants can eat as much as they want (self-select how much food they wish to eat)	30
Total	54

Withdrawals & dropouts

Period	Reason	FG000	FG001
Chamber at 24°C, ad Libitum Diet	Adverse Event	2	1
Chamber at 24°C, ad Libitum Diet	Withdrawal by Subject	3	2

Baseline characteristics

Characteristic	2. Chamber at 19°C, ad Libitum Diet First	Total	Chamber at 19°C With Fixed Diet First
Age, Continuous	37.8 years STANDARD_DEVIATION 10.9	36.5 years STANDARD_DEVIATION 10.3	34.9 years STANDARD_DEVIATION 9.4
Race (NIH/OMB) American Indian or Alaska Native	19 Participants	33 Participants	14 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	5 Participants	8 Participants	3 Participants
Race (NIH/OMB) More than one race	0 Participants	1 Participants	1 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants	8 Participants	4 Participants
Race (NIH/OMB) White	2 Participants	4 Participants	2 Participants
Sex: Female, Male Female	12 Participants	22 Participants	10 Participants
Sex: Female, Male Male	18 Participants	32 Participants	14 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 24	0 / 30
other Total, other adverse events	2 / 24	1 / 30
serious Total, serious adverse events	0 / 24	0 / 30

Outcome results

Primary

24-hour Energy Expenditure (kcal)

Energy expenditure (EE) as measured during 24 hours in a whole-room calorimeter

Time frame: Days 6 (Chamber at 24°C, fixed diet), 10(Chamber at 24°C, ad libitum diet), 14(Chamber at 19°C, fixed or ad libitum diet), 18(Chamber at 19°C, fixed or ad libitum diet), and 21(Chamber at 24°C, fasting)

Arm	Measure	Group	Value (MEAN)	Dispersion
Chamber at 19°C With Fixed Diet First	24-hour Energy Expenditure (kcal)	Chamber at 19°C, fixed diet	2271 kcal	Standard Deviation 360
Chamber at 19°C With Fixed Diet First	24-hour Energy Expenditure (kcal)	Chamber at 19°C, ad libitum diet	2552 kcal	Standard Deviation 418
Chamber at 19°C With Fixed Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, ad libitum diet	2563 kcal	Standard Deviation 422
Chamber at 19°C With Fixed Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, fasting	2135 kcal	Standard Deviation 337
Chamber at 19°C With Fixed Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, fixed diet	2256 kcal	Standard Deviation 393
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, fasting	1998 kcal	Standard Deviation 296
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, fixed diet	2166 kcal	Standard Deviation 302
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Expenditure (kcal)	Chamber at 24°C, ad libitum diet	2487 kcal	Standard Deviation 385
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Expenditure (kcal)	Chamber at 19°C, ad libitum diet	2505 kcal	Standard Deviation 401
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Expenditure (kcal)	Chamber at 19°C, fixed diet	2153 kcal	Standard Deviation 304

Primary

24-hour Energy Intake (kcal)

Energy intake as measured during 24 hours in a whole-room calorimeter

Arm	Measure	Group	Value (MEAN)	Dispersion
Chamber at 19°C With Fixed Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, fixed diet	3811 kcal	Standard Deviation 1140
Chamber at 19°C With Fixed Diet First	24-hour Energy Intake (kcal)	Chamber at 19°C, fixed diet	4014 kcal	Standard Deviation 1136
Chamber at 19°C With Fixed Diet First	24-hour Energy Intake (kcal)	Chamber at 19°C, ad libitum diet	4509 kcal	Standard Deviation 1255
Chamber at 19°C With Fixed Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, fasting	3795 kcal	Standard Deviation 1223
Chamber at 19°C With Fixed Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, ad libitum diet	4091 kcal	Standard Deviation 1054
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, ad libitum diet	4359 kcal	Standard Deviation 1404
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, fasting	4112 kcal	Standard Deviation 1406
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Intake (kcal)	Chamber at 19°C, fixed diet	4075 kcal	Standard Deviation 1587
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Intake (kcal)	Chamber at 24°C, fixed diet	3694 kcal	Standard Deviation 1503
2. Chamber at 19°C, ad Libitum Diet First	24-hour Energy Intake (kcal)	Chamber at 19°C, ad libitum diet	4762 kcal	Standard Deviation 1610

Secondary

24- Hour Respiratory Quotient (RQ)

RQ, an approximation for the ratio of carbohydrate-to-fat oxidation rates, is measured while in the chamber

Arm	Measure	Group	Value (MEAN)	Dispersion
Chamber at 19°C With Fixed Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, ad libitum diet	0.925 ratio	Standard Deviation 0.056
Chamber at 19°C With Fixed Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 19°C, ad libitum diet	0.909 ratio	Standard Deviation 0.037
Chamber at 19°C With Fixed Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 19°C, fixed diet	0.872 ratio	Standard Deviation 0.02
Chamber at 19°C With Fixed Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, fasting	0.793 ratio	Standard Deviation 0.022
Chamber at 19°C With Fixed Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, fixed diet	0.868 ratio	Standard Deviation 0.024
2. Chamber at 19°C, ad Libitum Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, fasting	0.789 ratio	Standard Deviation 0.03
2. Chamber at 19°C, ad Libitum Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, fixed diet	0.868 ratio	Standard Deviation 0.029
2. Chamber at 19°C, ad Libitum Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 24°C, ad libitum diet	0.935 ratio	Standard Deviation 0.06
2. Chamber at 19°C, ad Libitum Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 19°C, fixed diet	0.867 ratio	Standard Deviation 0.032
2. Chamber at 19°C, ad Libitum Diet First	24- Hour Respiratory Quotient (RQ)	Chamber at 19°C, ad libitum diet	0.916 ratio	Standard Deviation 0.045

Secondary