Dinner Time for Obesity and Prediabetes

Study Overview
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Brief Summary
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Obesity and its metabolic complications are leading causes of global morbidity and mortality. Evidence is mounting that inappropriate timing of food intake contributes to obesity. Specifically, late eating is associated with greater weight gain and metabolic syndrome. However, the mechanism by which late eating harms metabolism is not fully understood but may be related to mis-timing of food intake in relation to the body's endogenous circadian rhythm. Conversely, harmonization of eating timing with endogenous circadian rhythm may optimize metabolic health. In this study the investigators will use gold-standard methods of characterizing circadian rhythm in humans to examine the metabolic impacts food timing relative to endogenous circadian rhythm.

Detailed Description
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This is a randomized, cross-over study that examines the metabolic impact of early vs late dinner, as defined by proximity of food intake to an individual's biological night as determined by dim light melatonin onset (DLMO) in normal-weight, healthy adult volunteers and in adults with obesity and prediabetes. Each participant will first undergo circadian phenotyping at the Johns Hopkins Bayview Clinical Research Unit (Baltimore, Maryland), with assessment of DLMO and core body temperature profile, as well as wrist actigraphy. Thereafter, participants will be crossover randomized to (1) a 24-hour metabolic chamber protocol where dinner is eaten 3 hours before DLMO (early dinner), or (2) a 24-hour metabolic chamber protocol where dinner is 1 hour eaten after DLMO (late dinner), both to be performed at the NIH Metabolic Clinical Research Unit (Bethesda, Maryland). The timing and nutritional contents of all meals, as well as sleep timing and duration, will be held constant. Oral [2H31] palmitate will be given with each dinner condition to quantify dietary fat oxidation. The 2 dinner conditions will occur in random order, with a 3- to 4-week washout period. The investigators are enrolling both Normal-Weight Healthy (NWH) and Obesity-Prediabetes (OPD) research participants. At this time (5/2023) the investigators are focusing on the NWH group.

Official Title
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Dinner Time for Obesity and Prediabetes

Conditions
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PreDiabetes, Obesity, Healthy

Intervention / Treatment
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* Behavioral: Early Dinner
* Behavioral: Late Dinner
* Drug: Early Dinner tracer
* Drug: Late Dinner tracer


Participation Criteria
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Eligibility Criteria
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The investigators are enrolling both Normal-Weight Healthy (NWH) and Obesity-Prediabetes (OPD) research participants. At this time (5/2023) the investigators are focusing on the NWH group. Inclusion Criteria: For the Normal-Weight Healthy (NWH) cohort: Healthy male and female adults, age 18-50, with BMI 18-24.9 kg/m2 inclusively For the Obesity-Prediabetes (OPD) cohort: Male and female adults, age 18-50, with BMI ≥30 kg/m2 and prediabetes All participants must be able to understand study procedures and to comply with the procedures for the entire length of the study. Exclusion Criteria: Sleep disorder including insomnia, untreated moderate-severe sleep apnea, restless leg syndrome, or narcolepsy Night shift work Extreme delayed sleep phase defined as self-reported routine bedtime later than 1:00 AM or having mid-sleep on free days later than 5:00 AM on the Munich Chronotype Questionnaire (MCTQ) or DLMO later than 24:00 Gastroesophageal reflux disease that affects ability to tolerate a dinner close to bedtime Active smoking Current drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements. Diabetes (type 1 or 2) or on any diabetes medications besides metformin Evidence of metabolic or cardiovascular disease, or disease that may influence metabolism (e.g. cancer, thyroid disease) Hemoglobin A1c ≥5.7% for NWH cohort; Hemoglobin A1c ≥6.5% for OPD cohort Hemoglobin < 10 g/dL Self-reported kidney disease Any known history of an inherited metabolic disorder Pregnant or lactating female (pregnancy test will be required prior to metabolic visits) Peri-menopausal or post-menopausal female as determined by follicle stimulating hormone of > 30 mIU/mL or fewer than 3 menstrual periods in 6 months Professional or collegiate athlete Travel across >1 time zone within a 3-month period before and during the protocol Weight less than 40 kg or more than 180 kg Gastrointestinal disorders that can lead to obstruction of the digestive tract (i.e. diverticular disease, history of bowel obstruction, inflammatory bowel disease, motility disorder) History of any surgical procedures in the gastrointestinal tract. Swallowing disorders Taking any prescription medication or other drug that may influence metabolism (e.g. diet/weight-loss medication, asthma medication, blood pressure medication, psychiatric medications, corticosteroids, or other medications at the discretion of the PI and/or study team) Chronic use of sedative hypnotics, anxiolytics, opiates Use of medications that can affect circadian rhythm (beta blockers, melatonin) Presence of a cardiac pacemaker or other implanted electro-medical devices Those who have to undergo strong electromagnetic field during the period of use of the ingestible thermosensor (i.e. MRI) Weight loss or gain of ≥ 5% of total body weight over the preceding 3 months Currently participating in a weight loss program Prior bariatric surgery Volunteers with strict dietary concerns (e.g. vegetarian or kosher diet, food allergies) History of significant intravenous access issues Non-English speaking individuals: The complexity of the instructions for various components of the study would make the study procedures difficult to follow in the setting of a language barrier. Other conditions or situations at the discretion of the PI

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early Dinner First<br>Participants will be served dinner and a stable isotope of oral [2H31] palmitate to measure fat oxidation, at an early dinner time (before DLMO). This arm will then cross-over to Late Dinner as the second metabolic visit. | Behavioral: Early Dinner<br>* Dinner before DLMO<br>Behavioral: Late Dinner<br>* Dinner after DLMO<br>Drug: Early Dinner tracer<br>* Stable isotope of oral [2H31] palmitate to measure fat oxidation, given with dinner before DLMO<br>Drug: Late Dinner tracer<br>* Stable isotope of oral [2H31] palmitate to measure fat oxidation, given with dinner after DLMO<br>|
| Experimental: Late Dinner First<br>Participants will be served dinner and a stable isotope of oral [2H31] palmitate to measure fat oxidation, at a late dinner time (after DLMO). This arm will then cross-over to Early Dinner as the second metabolic visit. | Behavioral: Early Dinner<br>* Dinner before DLMO<br>Behavioral: Late Dinner<br>* Dinner after DLMO<br>Drug: Early Dinner tracer<br>* Stable isotope of oral [2H31] palmitate to measure fat oxidation, given with dinner before DLMO<br>Drug: Late Dinner tracer<br>* Stable isotope of oral [2H31] palmitate to measure fat oxidation, given with dinner after DLMO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour total fat oxidation | Within-subject difference in total fat oxidation between early dinner and late dinner conditions. | baseline, 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4-hour post-prandial area-under-the-curve (AUC) glucose levels | Within-subject difference in post-prandial AUC glucose levels between early dinner and late dinner conditions. | baseline, 4 weeks | 
| 4-hour post-prandial area-under-the-curve insulin levels | Within-subject difference in post-prandial AUC insulin levels between early dinner and late dinner conditions. | baseline, 4 weeks | 
| 14-hour post-dinner cumulative dietary fat oxidation | Within-subject difference in dietary fat oxidation between early dinner and late dinner conditions. | baseline, 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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circadian, sleep, glucose, metabolism