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

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.

Study Overview

• Status: Completed
• Conditions: Aging; Sleep Restriction; Circadian Disruption
• Intervention / Treatment: Behavioral: Circadian Disruption; Behavioral: Sleep Restriction; Behavioral: Control

Detailed Description

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
• Enrollment (Actual): 21
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Chronic circadian disruption; 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; 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).
EXPERIMENTAL: Chronic sleep restriction; 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; 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).
ACTIVE_COMPARATOR: Control (sleep extension); 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; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Xin Q, Yuan RK, Zitting KM, Wang W, Purcell SM, Vujovic N, Ronda JM, Quan SF, Williams JS, Buxton OM, Duffy JF, Czeisler CA. Impact of chronic sleep restriction on sleep continuity, sleep structure, and neurobehavioral performance. Sleep. 2022 Jul 11;45(7):zsac046. doi: 10.1093/sleep/zsac046.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 31, 2014
• Primary Completion (ACTUAL): April 1, 2019
• Study Completion (ACTUAL): April 1, 2019

Study Registration Dates

• First Submitted: June 16, 2014
• First Submitted That Met QC Criteria: June 23, 2014
• First Posted (ESTIMATE): June 24, 2014

Study Record Updates

• Last Update Posted (ACTUAL): August 20, 2019
• Last Update Submitted That Met QC Criteria: August 16, 2019
• Last Verified: August 1, 2019

More Information

Terms related to this study

• Keywords: Genetic; Sleep; Aging; Alertness; Metabolism; Circadian
• Other Study ID Numbers: 2014-P-000243; 2P01AG009975-16A1 (NIH)