Development of Countermeasures Against Adverse Metabolic Effects of Shift Work

Study Overview
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Brief Summary
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The goal of this application is to determine whether changing the timing of food intake prevents the adverse metabolic effects of circadian misalignment.

Detailed Description
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Shift work is associated with circadian misalignment and an increased risk for the development diabetes, obesity, and cardiovascular disease. This research will determine whether changing the feeding schedule can prevent metabolic alterations that can lead to the abovementioned disorders. This research will provide mechanistic insight and may provide a novel therapeutic approach against the increased risk for diabetes, obesity, and cardiovascular disease among shift workers.

Official Title
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Development of Countermeasures Against Adverse Metabolic Effects of Shift Work

Conditions
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Circadian Dysregulation

Intervention / Treatment
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* Behavioral: Meal schedule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: BMI between 18.5 and 29.9 kgm-2 Healthy adults with regular sleep-wake timing Non-smokers Completion of medical and psychological screening tests Able to spend 14 consecutive days in the sleep laboratory Exclusion Criteria: BMI <18.5 or > 29.9 kgm-2 History of neurological or psychiatric disorder History of sleep disorder or regular use of sleep-promoting medication Current prescription, herbal, or over-the-counter medication use Traveling across 2 or more time zones within past 3 months Donating blood within past 8 weeks Worked night or rotating shift work within past 3 years Hearing impairment Drug or alcohol dependency

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental<br>During Forced Desynchrony sleep and wake will occur at different circadian phases, while meals are restricted to the biological day. | Behavioral: Meal schedule<br> <br> |
| Other: Control<br>During Forced Desynchrony sleep and wake, as well as meals, will occur at different circadian phases. | Behavioral: Meal schedule<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in plasma leptin levels across sleep/wake cycle | Frequent blood samples | During circadian alignment (Day 7) and circadian misalignment (Day 10-11) | 
| Change in circadian profile of plasma leptin | Frequent blood samples | During constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13) | 
| Change in glucose tolerance | Frequent blood samples before and after standardized meals | During circadian alignment (Day 7) and circadian misalignment (Day 10-11) | 
| Change in circadian profile of plasma glucose levels | Frequent blood samples | During circadian alignment (Day 7) and circadian misalignment (Day 10-11) | 
| Change in plasma insulin levels after standardized test meal | Frequent blood samples before and after standardized meals | During circadian alignment (Day 7) and circadian misalignment (Day 10-11) | 
| Change in circadian profile of plasma insulin levels | Frequent blood samples | During circadian alignment (Day 7) and circadian misalignment (Day 10-11) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| o Change in circadian phase markers, such as from core body temperature, melatonin, and cortisol | Core temperature sensor throughout protocol, days 1-14. Frequent blood samples during constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13) | Core temperature and frequent blood samples | 
| Changes circadian rhythm in resting energy expenditure | Indirect calorimetry | During constant routine before forced desynchrony (Days 3-4) and constant routine after forced desynchrony (Days 12-13) | 
| Change in hunger and appetite, mood, and cognitive performance | Subjective hunger ratings and cognitive tests performed via computer interface | Tests taken throughout the protocol, days 1-14 | 
| Changes in microbiota, gene expression, epigenetic or proteomic markers | Frequent blood samples and saliva samples | samples taken during forced desychrony (days 7-11) and the constant routine protocols (days 3-4 and 11-13) | 
| Changes in sleep | Polysomnography | sleep periods following day 1, days 6-7 and days 10-11 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circadian Misalignment, Forced Desynchrony, Metabolism, Meal-timing, Circadian