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This project is designed to test for the first time whether glucose metabolism is differentially impaired by sleep restriction with and without additional exposure to artificial light at night (ALAN).
Laboratory studies have shown that sleep restriction to 4-6h per night for durations varying from one to 14 days reduces glucose tolerance in otherwise healthy adults, but the mechanisms by which insufficient sleep impairs glucose metabolism are still unknown. Current theories are based on the premise that the adverse metabolic consequences are caused by reduction in the duration of sleep per se. However, sleep curtailment is typically accompanied by longer exposure to artificial light at night (ALAN), which is an environmental endocrine disrupter that profoundly disrupts circadian rhythms.
The investigators have previously reported that acute circadian misalignment induced hyperglycemia comparable to pre-diabetic states in a third of otherwise healthy participants. Since then, the investigators have shown that even when the circadian phase of participants was realigned, prior exposure to 2 ½ weeks of chronic sleep restriction combined with a history of recurrent circadian disruption induced even more deleterious effects on glucose metabolism, in which pancreatic beta cells failed to respond adequately to increased glucose levels. Moreover, both night and rotating shift work (which induce circadian disruption) are associated with increased risk for metabolic problems. Night shifts can lead to acute increases in glucose and insulin levels, although some studies report reduced insulin release in response to meals consumed during the night. Given that circadian disruption has been shown to independently adversely affect metabolism, and exposure to ALAN adversely impacts metabolism in animals, it is important to understand the extent to which circadian disruption contributes to the observed impact of sleep curtailment on metabolism. No previous studies of the metabolic impact of sleep restriction in humans have controlled for this additional exposure to ALAN, thus confounding the effects of sleep restriction with the effects of circadian disruption caused by extended exposure to ALAN.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sleep Restriction with ALAN, then Sleep Restriction without ALAN | Experimental | Participants first received Sleep Restriction with extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction without ALAN, during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). |
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| Sleep Restriction without ALAN, then Sleep Restriction with ALAN | Experimental | Participants first received Sleep Restriction without extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction with extended duration ALAN, during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Sleep Restriction with ALAN first, then Sleep Restriction without ALAN | Other | Sleep restriction with 90 lux lighting for 19hr/day first, followed by Sleep restriction with 90 lux lighting for 14hr/day |
| Measure | Description | Time Frame |
|---|---|---|
| Impairment of Insulin Sensitivity | Insulin sensitivity (Si) is assessed via minimal model analysis, a mathematical model developed by Bergman and colleagues. Higher values represent better insulin sensitivity and lower values represent impaired insulin sensitivity. The mean change in Si between exposure and baseline is reported for each arm. | Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32 |
| Impairment of Glucose Tolerance | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will induce greater impairment of glucose tolerance than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Glucose tolerance will be calculated as the area under the curve from minutes 0-120 following a mixed meal tolerance test | Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31 |
| Duration of Nocturnal Melatonin Secretion | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will acutely reduce the duration of nocturnal melatonin secretion as compared to baseline more than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Duration of nocturnal melatonin secretion will be determined by the duration of time at which melatonin levels are above a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light. | Change between Study Day 14-15 (overnight) vs. Study Day 31-32 (overnight) |
| Measure | Description | Time Frame |
|---|---|---|
| Acute Insulin Response to Glucose | Acute Insulin Response as calculated with minimal model analysis, a mathematical model developed by Bergman and colleagues, and represents early insulin release in the body to manage blood glucose levels. Higher values represent a better response and lower values represent a worse response. The mean change in AIRg between exposure and baseline is reported for each arm. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Charles A Czeisler, PhD, MD | Brigham and Women's Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
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Two participants were excluded prior to randomization; one was due to an undisclosed surgery that excluded them from the study, and the other was due to ending study enrollment before they were admitted.
Healthy volunteers were recruited through online advertisements between October 2021-December 2023.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sleep Restriction With ALAN, Then Sleep Restriction Without ALAN | Participants first received Sleep Restriction with extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction without ALAN, during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 26, 2024 |
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This study uses a within-subjects randomized crossover design to compare the effects of sleep restriction with and without ALAN on glucose metabolism. The order in which subjects undergo the two sleep interventions will be randomized.
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The order in which subjects undergo the two sleep interventions will be randomized.
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| Sleep Restriction without ALAN first, then sleep restriction with ALAN | Other | Sleep restriction with 90 lux lighting for 14hr/day first, followed by Sleep restriction with 90 lux lighting for 19hr/day |
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| Change from study day 7 to 15 compared to change from study day 24 to 32 |
| Glucose Effectiveness | Glucose Effectiveness as calculated using minimal model analysis, a mathematical model developed by Bergman and colleagues. It represents how well the body can normalize blood glucose independent of insulin. Higher glucose effectiveness (Sg) is generally associated with better metabolic health outcomes. | Change from study day 7 to 15 vs change from study day 24 to 32 |
| Insulin Area-under-the-curve | Insulin area under the curve (AUC) as calculated with trapezoidal method between 0-120min following mixed meal tolerance test. | Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31 |
| Duration of Endogenous Melatonin Secretory Profile | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will reduce the duration of the endogenous melatonin secretory profile more than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Duration of nocturnal melatonin secretion will be determined by the duration of time at which melatonin levels are above a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light. | Study Day 15-16 vs Study Day 32-33 |
| FG001 | Sleep Restriction Without ALAN, Then Sleep Restriction With ALAN | Participants first received Sleep Restriction without extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction with extended duration ALAN, during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). |
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| NOT COMPLETED |
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10 participants were included in analyses. We were unable to obtain baseline measures for 2 participants who were randomized but did not complete. We were also unable to perform the IVGTT in 1 participant in the Sleep Restriction without ALAN, then Sleep Restriction with ALAN group so analyzed only 4 participants for outcome measures which used minimal model analysis. For other outcomes (e.g. melatonin duration and glucose tolerance), all 5 participants in this group were included.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sleep Restriction Without ALAN, Then Sleep Restriction With ALAN | Participants first received Sleep Restriction without extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction with extended duration ALAN, during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). |
| BG001 | Sleep Restriction With ALAN, Then Sleep Restriction Without ALAN | Participants first received Sleep Restriction with extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). After a washout of 10 days, participants received Sleep Restriction without extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants | No |
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| Region of Enrollment | Number | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Impairment of Insulin Sensitivity | Insulin sensitivity (Si) is assessed via minimal model analysis, a mathematical model developed by Bergman and colleagues. Higher values represent better insulin sensitivity and lower values represent impaired insulin sensitivity. The mean change in Si between exposure and baseline is reported for each arm. | One participant excluded from "Without ALAN" condition due to non-physiological assay results | Posted | Mean | Standard Deviation | (mU/L)^-1 min^-1 | Change between Study Day 7 vs. Study Day 15 and Study Day 24 vs. Study Day 32 |
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| Primary | Impairment of Glucose Tolerance | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will induce greater impairment of glucose tolerance than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Glucose tolerance will be calculated as the area under the curve from minutes 0-120 following a mixed meal tolerance test | Posted | Mean | Standard Deviation | mg/dL*min | Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31 |
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| Primary | Duration of Nocturnal Melatonin Secretion | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will acutely reduce the duration of nocturnal melatonin secretion as compared to baseline more than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Duration of nocturnal melatonin secretion will be determined by the duration of time at which melatonin levels are above a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light. | Unable to calculate melatonin duration for one participant under the Without ALAN condition due to IV sampling difficulties | Posted | Mean | Standard Deviation | minutes | Change between Study Day 14-15 (overnight) vs. Study Day 31-32 (overnight) |
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| Secondary | Acute Insulin Response to Glucose | Acute Insulin Response as calculated with minimal model analysis, a mathematical model developed by Bergman and colleagues, and represents early insulin release in the body to manage blood glucose levels. Higher values represent a better response and lower values represent a worse response. The mean change in AIRg between exposure and baseline is reported for each arm. | Posted | Mean | Standard Deviation | (mU/L)^-1 min^-1 | Change from study day 7 to 15 compared to change from study day 24 to 32 |
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| Secondary | Glucose Effectiveness | Glucose Effectiveness as calculated using minimal model analysis, a mathematical model developed by Bergman and colleagues. It represents how well the body can normalize blood glucose independent of insulin. Higher glucose effectiveness (Sg) is generally associated with better metabolic health outcomes. | Posted | Mean | Standard Deviation | min^-1 | Change from study day 7 to 15 vs change from study day 24 to 32 |
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| Secondary | Insulin Area-under-the-curve | Insulin area under the curve (AUC) as calculated with trapezoidal method between 0-120min following mixed meal tolerance test. | We were unable to obtain meal response data for 2 participants due to IV access issues. | Posted | Mean | Standard Deviation | uIu/mL*min | Change between Study Day 6 vs. Study Day 14 and Study Day 23 vs. Study Day 31 |
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| Secondary | Duration of Endogenous Melatonin Secretory Profile | Test the hypothesis that exposure to one week of sleep restriction with concurrent exposure to extended duration ALAN (LD 19:5) will reduce the duration of the endogenous melatonin secretory profile more than exposure to one week of sleep restriction without extended duration ALAN (LD 14:10). Duration of nocturnal melatonin secretion will be determined by the duration of time at which melatonin levels are above a threshold calculated as 25% of peak-to-trough amplitude at baseline in dim light. | Posted | Mean | Standard Deviation | minutes | Study Day 15-16 vs Study Day 32-33 |
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From admission to inpatient study until the participant's last inpatient day (up to 33 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sleep Restriction With ALAN | Participants received Sleep Restriction with extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours and participants remained in room lighting for the full wake episode (19h room light, 5h darkness). | 0 | 12 | 0 | 12 | 2 | 12 |
| EG001 | Sleep Restriction Without ALAN | Participants received Sleep Restriction without extended duration Artificial Light At Night (ALAN), during which sleep episodes were shortened to 5 hours but participants were kept in dim light for the extra time awake (14h room light, 5h dim light, 5h darkness). | 0 | 12 | 0 | 12 | 6 | 12 |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
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| Lightheadedness | General disorders | Systematic Assessment |
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| Nausea | General disorders | Systematic Assessment |
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| Bruising/petechiae on arm | General disorders | Systematic Assessment |
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| Chest pressure | General disorders | Systematic Assessment |
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| Stomach pain | General disorders | Systematic Assessment |
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Study enrollment was ended early due to budgetary reasons, so we were unable to study the total number of participants planned. Thus, we may have limited statistical power to interpret the results.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Charles Czeisler, Ph.D., M.D. | Brigham and Women's Hospital | 617-732-4013 | cacadmin@partners.org |
| May 23, 2025 |
| Prot_SAP_000.pdf |
| ID | Term |
|---|---|
| D018149 | Glucose Intolerance |
| D012892 | Sleep Deprivation |
| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D020920 | Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001523 | Mental Disorders |
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| >=65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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| Participants |
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