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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
21
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).
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).
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.
Brigham and Women's Hospital
Boston, Massachusetts, United States
Change in insulin sensitivity
Euglycemic hyperinsulinemic clamp-assessed measure of insulin sensitivity
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: Baseline day 2, at 3 weeks of exposure, and 1 week into recovery
Change in resting metabolic rate
Indirect calorimetry, daily body weight, core body temperature
Time frame: 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)
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Time frame: 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
Time frame: Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery
Change in neurocognitive performance
Cognitive test battery presented via computer interface
Time frame: Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery
Changes in perception of pain, hunger and sleepiness
Daily questionnaires
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Daily throughout the 3-day baseline, last 3 days of the 3-week exposure, and last three days of the 1-week recovery