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Completed

NCT Number: NCT02171273

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.

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Key information

Age range

21 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Circadian Disruption

Behavioral

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).

Sleep Restriction

Behavioral

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).

Control

Behavioral

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.

Primary outcomes

  1. Change in insulin sensitivity

    Time frame: Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery

    Euglycemic hyperinsulinemic clamp-assessed measure of insulin sensitivity

  2. Changes in glucose levels after standardized meal

    Time frame: Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery

    Frequent blood samples during and after standardized meal (breakfast), response of blood glucose levels

  3. Change in insulin levels after standardized meal

    Time frame: Baseline day 2, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery

    Frequent blood samples during and after standardized meal (breakfast)

  4. Change in 24h profiles of leptin

    Time frame: Baseline day 2, during acute circadian misalignment (exposure day 3), and acute realignment (exposure day 7)

    Hourly blood samples for 24 hours

  5. Change in 24h profiles of cortisol

    Time frame: Baseline day 2, at 3 weeks of exposure, and 1 week into recovery

    Hourly blood samples for 24 hours

Secondary outcomes

  1. Change in resting metabolic rate

    Time frame: Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery

    Indirect calorimetry, daily body weight, core body temperature

  2. Change in circadian phase and/or period

    Time frame: Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery

    Via measurement of core body temperature and melatonin (salivary and plasma)

  3. Changes in sleep/wake architecture and brain electrical activity

    Time frame: Continuous throughout the 3-day baseline, 3-week exposure, and 1-week recovery

    Polysomnography during sleep and wake

  4. Change in neurocognitive performance

    Time frame: Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery

    Cognitive test battery presented via computer interface

  5. Changes in perception of pain, hunger and sleepiness

    Time frame: Daily throughout the 3-day baseline, 3-week exposure, and 1-week recovery

    Daily questionnaires

  6. Change in inflammatory markers and wake-time hormone levels

    Time frame: Baseline days 2 and 3, daily throughout 1st and 3rd weeks of exposure, and 1 week into recovery

    Measurements on fasted blood samples

  7. Changes in daily patterns of gene expression, epigenetic or proteomic markers

    Time frame: Baseline day 2, at 1 week and at 3 weeks of exposure, and 1 week into recovery

    Blood samples collected every 4 hours for 48 hours

  8. Changes in measures of sympathovagal balance and autonomic function

    Time frame: Baseline day 3, at 1 week and at 3 weeks of exposure, and 1 week into recovery

    EKG, urinary catecholamines, fasting and postprandial blood samples for cortisol, epinephrine and norepinephrine

  9. Change in nutrient absorption

    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

    Bomb calorimetry on stool samples

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • National Institute on Aging (NIA)

Registry information

Important dates

Study start
2014
Primary completion
2019
Study completion
2019
First posted
Jun 24, 2014
Registry last updated
Aug 20, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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