NCT02939404

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

Completed NA Results posted Last updated 4 July 2025

What this trial tests

NA trial testing Cold exposure in Healthy Volunteers in 54 participants. Completed in 24 June 2024.

Timeline

27 April 2017

Primary endpoint
24 June 2024

24 June 2024

Quick facts

Lead sponsor	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	crossover
Masking	none
Primary purpose	basic science
Enrollment	54
Start date	27 April 2017
Primary completion	24 June 2024
Estimated completion	24 June 2024
Sites	1 location across United States

Drugs / interventions tested

• Cold exposure
• Normal temperature
• Fixed diet
• Ad libitum diet
• Fasting

Conditions studied

• Healthy Volunteers — all drugs for Healthy Volunteers →

Sponsor

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

Who can join

Adults 18 to 55, any sex, with Healthy Volunteers. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

24-hour Energy Expenditure (kcal) Primary · 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

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	2256	± 393
2. Chamber at 19°C, ad Libitum Diet First	2166	± 302

Chamber at 24°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	2563	± 422
2. Chamber at 19°C, ad Libitum Diet First	2487	± 385

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	2271	± 360
2. Chamber at 19°C, ad Libitum Diet First	2153	± 304

Chamber at 19°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	2552	± 418
2. Chamber at 19°C, ad Libitum Diet First	2505	± 401

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	2135	± 337
2. Chamber at 19°C, ad Libitum Diet First	1998	± 296

24-hour Energy Intake (kcal) Primary · 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

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	3811	± 1140
2. Chamber at 19°C, ad Libitum Diet First	3694	± 1503

Chamber at 24°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	4091	± 1054
2. Chamber at 19°C, ad Libitum Diet First	4359	± 1404

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	4014	± 1136
2. Chamber at 19°C, ad Libitum Diet First	4075	± 1587

Chamber at 19°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	4509	± 1255
2. Chamber at 19°C, ad Libitum Diet First	4762	± 1610

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	3795	± 1223
2. Chamber at 19°C, ad Libitum Diet First	4112	± 1406

24- Hour Respiratory Quotient (RQ) Secondary · 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

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.868	± 0.024
2. Chamber at 19°C, ad Libitum Diet First	0.868	± 0.029

Chamber at 24°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.925	± 0.056
2. Chamber at 19°C, ad Libitum Diet First	0.935	± 0.06

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.872	± 0.02
2. Chamber at 19°C, ad Libitum Diet First	0.867	± 0.032

Chamber at 19°C, ad libitum diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.909	± 0.037
2. Chamber at 19°C, ad Libitum Diet First	0.916	± 0.045

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.793	± 0.022
2. Chamber at 19°C, ad Libitum Diet First	0.789	± 0.03

Leptin Secondary · 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)

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	26.1	± 26.4
2. Chamber at 19°C, ad Libitum Diet First	26.5	± 30.5

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	29.5	± 30.1
2. Chamber at 19°C, ad Libitum Diet First	27.8	± 30.3

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	18.3	± 19.9
2. Chamber at 19°C, ad Libitum Diet First	16.6	± 22.1

Secretin Secondary · 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)

(Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.91	± 0.22
2. Chamber at 19°C, ad Libitum Diet First	0.91	± 0.25

(Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	1.03	± 0.26
2. Chamber at 19°C, ad Libitum Diet First	1.00	± 0.25

(Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.99	± 0.24
2. Chamber at 19°C, ad Libitum Diet First	1.01	± 0.24

Ghrelin Secondary · 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)

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	502	± 254
2. Chamber at 19°C, ad Libitum Diet First	644	± 274

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	544	± 277
2. Chamber at 19°C, ad Libitum Diet First	605	± 311

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	575	± 293
2. Chamber at 19°C, ad Libitum Diet First	581	± 304

FGF-21 Secondary · 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)

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	94	± 73
2. Chamber at 19°C, ad Libitum Diet First	98	± 72

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	98	± 81
2. Chamber at 19°C, ad Libitum Diet First	113	± 90

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	106	± 66
2. Chamber at 19°C, ad Libitum Diet First	108	± 76

Core Body Temperature (C) Secondary · 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

Chamber at 24°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	36.98	± 0.15
2. Chamber at 19°C, ad Libitum Diet First	37.02	± 0.17

Chamber at 19°C, fixed diet

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	36.97	± 0.19
2. Chamber at 19°C, ad Libitum Diet First	36.95	± 0.20

Chamber at 24°C, fasting

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	36.98	± 0.21
2. Chamber at 19°C, ad Libitum Diet First	36.98	± 0.21

Weight Change at 6 Months Secondary · 6 months

Weight change from baseline to 6 months

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	0.3	± 5.6
2. Chamber at 19°C, ad Libitum Diet First	-0.5	± 8.1

Weight Change at 12 Months Secondary · 12 months

Weight change from baseline to 12 months

Group	Value	95% CI
Chamber at 19°C With Fixed Diet First	1.0	± 8.9
2. Chamber at 19°C, ad Libitum Diet First	-0.6	± 8.9

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 year. Reporting threshold: 1%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Chamber at 19°C With Fixed Diet First

Serious: 0/24 (0%)

Deaths: 0/24

2. Chamber at 19°C, ad Libitum Diet First

Serious: 0/30 (0%)

Deaths: 0/30

Other adverse events (2 terms — click to expand)

Reaction	System	Chamber at 19°C With Fixed…	2. Chamber at 19°C, ad Lib…
Gastroesophageal reflux disease symptoms at Chamber at 24°C, fixed diet	Gastrointestinal disorders	—	—
Gastroesophageal reflux disease symptoms at Chamber at 19°C, fixed diet	Gastrointestinal disorders	—	—

Data from ClinicalTrials.gov NCT02939404 adverse events section.

Sponsor's own description

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.

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

1. Metabolic Responses to 24-Hour Fasting and Mild Cold Exposure in Overweight Individuals Are Correlated and Accompanied by Changes in FGF21 Concentration.
   Hollstein T, Heinitz S, Ando T, Rodzevik TL, et al · · 2020 · cited 17× · PMID 32341039 · DOI 10.2337/db20-0153
2. Recharacterizing the Metabolic State of Energy Balance in Thrifty and Spendthrift Phenotypes.
   Hollstein T, Basolo A, Ando T, Votruba SB, et al · · 2020 · cited 16× · PMID 32118268 · DOI 10.1210/clinem/dgaa098
3. Impaired metabolic flexibility to fasting is associated with increased ad libitum energy intake in healthy adults.
   Unlu Y, Piaggi P, Stinson EJ, Cabeza De Baca T, et al · · 2024 · cited 5× · PMID 38650517 · DOI 10.1002/oby.24011
4. Cold induces increased ad libitum energy intake independent of changes in energy expenditure: a controlled crossover trial in adults.
   Unlu Y, Piaggi P, Stinson EJ, De Baca TC, et al · · 2025 · cited 1× · PMID 39675563 · DOI 10.1016/j.ajcnut.2024.12.013
5. Hunger on the Three-Factor Eating Questionnaire Is Associated With Increased Ad Libitum Energy Intake in Different Conditions.
   Fry HT, Gluck ME, de Baca TC, Stinson EJ, et al · · 2026 · PMID 41709501 · DOI 10.1002/oby.70148