Impact of Chronic Circadian Disruption vs. Chronic Sleep Restriction on Metabolism

Study Overview
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Brief Summary
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The overall objectives of the proposed study are to examine the consequences of chronic circadian disruption and chronic sleep restriction on metabolic function in healthy adults.

Detailed Description
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It has long been recognized that sleep patterns change with age. A common feature of aging is the advance of the timing of sleep to earlier hours, often earlier than desired. These age-related changes are found in even healthy individuals who are not taking medications and who are free from sleep disorders. In addition to these sleep disturbances, many older individuals curtail their sleep voluntarily, reporting similar rates of sleep restriction (sleeping less than 7 or less than 6 hours per night) when compared to young adults. Whether voluntary or not, insufficient sleep has medical, safety and metabolic consequences. In fact, converging evidence in young adults suggests that sleep restriction per se may impair metabolism, and that reduced sleep duration is associated with weight gain, obesity, diabetes, cardiovascular disease, and mortality. An understanding of how the circadian and sleep homeostatic neurobiological processes responds to increasing homeostatic sleep pressure, and the effects of sleep restriction on metabolism at different ages, should provide information on the regulation of sleep and metabolism in aging, as well as direction for future treatments. In the present study, we will study the separate impacts of chronic sleep restriction (while minimizing circadian disruption) and chronic circadian disruption (while minimizing sleep disruption) and a poor diet on metabolism.

Official Title
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Impact of Chronic Circadian Disruption vs. Chronic Sleep Restriction on Metabolism

Conditions
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Aging, Sleep Restriction, Circadian Disruption

Intervention / Treatment
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* Behavioral: Circadian Disruption
* Behavioral: Sleep Restriction
* Behavioral: Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adults with conventional and regular sleep-wake timing Non-smokers Completion of medical, psychological, and sleep screening tests Able to spend 37 consecutive days/nights in the laboratory Exclusion Criteria: 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: 21 Years
Maximum Age: 70 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: Chronic circadian disruption<br>Following a baseline of adequate time in bed, study participants will spend 3 weeks on a daily jet-lag schedule (where each day is longer than 24 hours). | Behavioral: Circadian Disruption<br>* Following a baseline of adequate time in bed, study participants will spend 3 weeks on a daily jet-lag schedule (where each day is longer than 24 hours).<br>|
| Experimental: Chronic sleep restriction<br>Following a baseline of adequate time in bed, study participants will have a shortened opportunity for sleep during each 24-hour day (for three weeks). | Behavioral: Sleep Restriction<br>* Following a baseline of adequate time in bed, study participants will have a shortened opportunity for sleep during each 24-hour day (for three weeks).<br>|
| Active Comparator: Control (sleep extension)<br>Following a baseline of adequate time in bed, study participants will continue to have adequate time in bed and opportunity for sleep during each 24-hour day, for 3 weeks. | Behavioral: Control<br>* Following a baseline of adequate time in bed, study participants will continue to have adequate time in bed and opportunity for sleep during each 24-hour day, for 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in insulin sensitivity | Euglycemic hyperinsulinemic clamp-assessed measure of insulin sensitivity | Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery | 
| Changes in glucose levels after standardized meal | Frequent blood samples during and after standardized meal (breakfast), response of blood glucose levels | Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | 
| Change in insulin levels after standardized meal | Frequent blood samples during and after standardized meal (breakfast) | Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | 
| Change in 24h profiles of leptin | Hourly blood samples for 24 hours | Baseline day 2, during acute circadian misalignment (exposure day 3), and acute realignment (exposure day 7) | 
| Change in 24h profiles of cortisol | Hourly blood samples for 24 hours | Baseline day 2, at 3 weeks of exposure, and 1 week into recovery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in resting metabolic rate | Indirect calorimetry, daily body weight, core body temperature | Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | 
| Change in circadian phase and/or period | Via measurement of core body temperature and melatonin (salivary and plasma) | Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery | 
| Changes in sleep/wake architecture and brain electrical activity | Polysomnography during sleep and wake | Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery | 
| Change in neurocognitive performance | Cognitive test battery presented via computer interface | Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery | 
| Changes in perception of pain, hunger and sleepiness | Daily questionnaires | Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery | 
| Change in inflammatory markers and wake-time hormone levels | Measurements on fasted blood samples | Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery | 
| Changes in daily patterns of gene expression, epigenetic or proteomic markers | Blood samples collected every 4 hours for 48 hours | Baseline day 2, at 1 week and at 3 weeks of exposure, and 1 week into recovery | 
| Changes in measures of sympathovagal balance and autonomic function | EKG, urinary catecholamines, fasting and postprandial blood samples for cortisol, epinephrine and norepinephrine | Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery | 
| Change in nutrient absorption | Bomb calorimetry on stool samples | Daily throughout the 3-day baseline, last 3 days of the 3-week exposure, and last three days of the 1-week recovery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep, Aging, Metabolism, Circadian, Genetic, Alertness