Circadian Misalignment and Energy Balance

Study Overview
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Brief Summary
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Preliminary findings from the investigators' lab suggest that circadian misalignment, occurring when meals and sleep are mistimed from one another, alters resting state neuronal processing in areas relevant to food reward and interoception; supporting a role of sleep and meal misalignment, on energy balance regulation. No study has been done to disentangle the effects of sleep and meal timing on body weight regulation, independent of sleep duration. This study will provide information to guide messaging related to timing of meals and sleep that can be translated to individuals whose sleep follows unconventional times, such as shift workers and those with jetlag and social jetlag.

Detailed Description
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The proposed study will test whether the misalignment of eating occasions to the sleep period influences health markers. The goal of the proposed study is to determine whether eating out of synchrony with sleep influences risk of chronic diseases. The proposed study has both mechanistic and translational objectives. First, the investigators will test whether eating late in the day will influence energy balance (hormones, energy expenditure, nutritional intakes). Next, they will observe how misaligned meals, relative to aligned meals, influence behavior. Overweight men and women will be recruited to participate in a 2-phase, crossover study, with constant sleep periods. Phases will only differ in the alignment of meals to the sleep period: aligned = meals starting 1 h after awakening; misaligned = meals starting 5 h after awakening. Mechanistic aims will be addressed from measurements taken after 3 and 14 d of the intervention. The translational aim will be addressed after a 4 wk free-living period following the prescribed meal times for each phase. This proposed study, which will manipulate meal timing, without affecting total sleep time, is important because it will provide information on the mechanism by which circadian misalignment influences health. As such, the proposed study will be a stepping-stone in the establishment of lifestyle recommendations or therapies to personalize chronotype to reduce the risk of chronic diseases.

Official Title
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Impact of Circadian Misalignment on Energy Balance Regulation

Conditions
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Obesity

Intervention / Treatment
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* Behavioral: Meal times


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All racial and ethnic groups Body mass index 25-34.9 kg/m2 Average sleep duration ≥7 hour/night, assessed during 2-week screening period Eat within 1 hour of awakening at least 5 days/week Midpoint of sleep at 4 AM or earlier Exclusion Criteria: <10 nights of sleep <7 hour during the 2-week screening period Daytime napping Current or past sleep disorder (Sleep Disorders Inventory); Insomnia Severity Index Score >10 Current or past psychiatric disorder, including eating disorders and seasonal affective disorder Any psychological or psychiatric disorder deemed to interfere with study outcomes Smoking (currently smoking any cigarettes or using tobacco products, e-cigarettes and vapes, or ex-smokers <3 years) Night and rotating shift work Travel across time zones within 4 wk of the study History of drug or alcohol abuse or excessive alcohol consumption (>3 drinks/day for men or 2 for women) Recent weight change (>5% gain or loss of body weight over past 3 months) or active participation in diet or weight loss program in previous 3 months; any weight loss procedure Pregnancy or <1 year post-partum Diagnosed sleep apnea or high-risk score on Berlin questionnaire (2 or more categories with positive score) Depression (score >13 on Beck Depression Inventory II) or taking anti-depressive medications Restless leg syndrome and circadian rhythm disorders Dementia or cognitive impairments Taking psychoactive or hypnotic medications Taking chronic analgesic or anti-inflammatory medications Having had gastrointestinal surgery, including gastric bypass surgery Restrained eating or abnormal scores on the Three Factor Eating Questionnaire Contraindications for magnetic resonance imaging scanning Hematocrit <30% Taking beta blockers, as this can interfere with melatonin secretion

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 49 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: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a 2-period crossover study in which sleep is identical in duration and timing but meals/food intake is varied relative to the sleep episode.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Circadian misalignment<br>Meals in this condition will be delayed by 4 hours relative to the circadian alignment condition. Food intake during this period will be from 1 PM to 11 PM. | Behavioral: Meal times<br>* Meal times vary based on the arm: aligned or misaligned<br>|
| Active Comparator: Circadian alignment<br>Meals in this condition will be aligned to the sleep episode. Food intake during this period will be from 9 AM to 7 PM. | Behavioral: Meal times<br>* Meal times vary based on the arm: aligned or misaligned<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Energy expenditure | Metabolic chamber | Change over 2-week period | 
| Body composition | Quantitative magnetic resonance | Change over 4-week period | 
| Nutritional intakes | 3-day food records | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Task-based functional neuroimaging | Brain responses to food stimuli | Change over 2-week period | 
| Resting state functional neuroimaging | Functional neuroimaging | Change over 2-week period | 
| Appetite | Visual analog scales | 4 weeks | 
| Hormones | Leptin, ghrelin, peptide tyrosine tyrosine, glucagon-like peptide 1 | Change over 2-week period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food intake, Energy expenditure, Body composition, Meal timing