Clinical trial NCT02939404: Food Intake Response to Short-Term Modifications of Metabolism in Humans
Official title: Energy Intake Response to Short-Term Alterations of Energy Expenditure in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy Volunteers
Keywords: Energy Intake
Energy Expenditure
Eating Behavior
Cold Exposure
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2016-10-20
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility 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)

Primary outcomes:
measure: 24-hour energy expenditure (kcal)
timeFrame: Days 6, 10, 14, 18, and 21
measure: 24-hour energy intake (kcal)
timeFrame: Days 7, 10, 14 or 18, 15 or 19, and 22
Secondary outcomes:
measure: 24- hour respiratory quotient (RQ)
timeFrame: Days 6, 10, 14, 18, and 21
measure: Leptin
timeFrame: Days 6, 14 or 18, 21
measure: Secretin
timeFrame: Days 6, 14 or 18, 21
measure: Ghrelin
timeFrame: Days 6, 14 or 18, 21
measure: FGF-21
timeFrame: Days 6, 14 or 18, 21
measure: Core body temperature (c)
timeFrame: Days 6, 14 or 18, 21
measure: Weight change at 6 months
timeFrame: 6 months
measure: Weight change at 12 months
timeFrame: 12 months
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: NIDDK, Phoenix
state: Arizona
Study officials:
affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
name: Douglas Chang, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hollstein T, Heinitz S, Ando T, Rodzevik TL, Basolo A, Walter M, Chang DC, Krakoff J, Piaggi P. Metabolic Responses to 24-Hour Fasting and Mild Cold Exposure in Overweight Individuals Are Correlated and Accompanied by Changes in FGF21 Concentration. Diabetes. 2020 Jul;69(7):1382-1388. doi: 10.2337/db20-0153. Epub 2020 Apr 27.
citation: 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.