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Reestablishing Sleep and Circadian Alignment in Medical Intensive Care Unit (MICU) Patients Via a Mechanistic RCT of an Sleep Chronobundle

Not Applicable
Recruiting
Conditions
Circadian Rhythm Sleep Disorder, Unspecified
Critical Illness
Sleep Deprivation
Interventions
Other: Chronobundle - light
Other: chronobundle - feeding
Other: chronobundle - mobility
Other: chronobundle - sleep
Registration Number
NCT05551325
Lead Sponsor
Yale University
Brief Summary

More than 5 million patients are admitted to the intensive care unit every year in the United States; most of these patients experience profound sleep and circadian disruption. Promotion of circadian alignment (i.e., alignment of the body's clocks) would make it possible to strategically schedule behaviors such as sleep and eating at normal body clock times, which is predicted to improve sleep quality and metabolic function. This project will test the ability of a sleep chronobundle (i.e., sleep promotion and circadian treatment bundle) to normalize circadian alignment and subsequently test if this realignment also improves sleep and metabolism.

Detailed Description

An evidence-based treatment that simultaneously addresses intensive care unit (ICU) sleep and circadian disruption (SCD) is desperately needed. Such treatment is needed because patients admitted to the ICU are at high risk for adverse outcomes resulting directly from acute SCD. It is well established among healthy controls that acute SCD is associated with immediate negative consequences such as metabolic, cognitive, cardiovascular, respiratory, skeletal muscle, and immune dysfunction. Normalization of sleep and circadian processes improves these dysfunctions. In the ICU, sleep and circadian processes cannot be segregated, and there are likely several overlapping domains of SCD (e.g., sleep duration, timing, architecture, and continuity, and circadian alignment and amplitude). Thus, a bundled approach to sleep and circadian promotion holds the most promise for reversing SCD, normalizing broader physiologic disruptions, and improving ICU outcomes.

To date, ICU sleep promotion bundles have had limited success in documenting improved sleep, and sleep bundles have commonly ignored circadian disruption and circadian-based sleep promotion strategies. This is a critical gap. Translation of circadian principles to ICU sleep promotion is essential because alignment between biologic and clock time allows for subsequent strategic scheduling of behaviors, for example, scheduling sleep promotion during the biologic night to improve sleep duration and quality. In addition, circadian alignment has broader physiologic implications and related potential to improve function across a wide variety of organ systems, for example, scheduling eating during the biologic day to improve glucose tolerance. Investigations to date have not tested the effect of a multifaceted intervention that includes promotion of both circadian alignment via photic and nonphotic zeitgebers and overnight sleep via non-pharmacologic strategies (sleep chronobundle).

The overall objective of this project is to test whether a sleep chronobundle, including daytime bright light, time-restricted daytime feeding, increased daytime mobility, and overnight sleep promotion mitigates ICU SCD. A mechanistic randomized controlled trial will be used to test our central hypotheses that a sleep chronobundle will (1) align biologic and clock day-night; (2) overlap behaviors (e.g., sleeping and eating) correctly with biologic time periods; and therefore (3) improve sleep and metabolic processes in the ICU. The focus of this study is on sleep and glucose metabolism metrics because of their high relevance to critical illness.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
160
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ChronobundleChronobundle - lightThe chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.
Chronobundlechronobundle - feedingThe chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.
Chronobundlechronobundle - mobilityThe chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.
Chronobundlechronobundle - sleepThe chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.
Primary Outcome Measures
NameTimeMethod
Circadian alignment based on diurnal heart rate variationpost-treatment, 72 hours

Individual heart rate nadir compared to population normal nadir of 04:00. Maximum difference +/- 12 hours.

Secondary Outcome Measures
NameTimeMethod
Overnight Rapid Eye Movement (REM) proportionpost-treatment, 72 hours

Proportion of Stage REM sleep from 22:00 to 05:59 as measured by NoxA1 portable polysomnography device.

Glucose tolerancepost-treatment, 72 hours

Area under the curve per 24 hour period of continuous glucose monitoring.

Urine 6-sulfatoxymelatonin acrophase change from normalpost-treatment, 72 hours

Individual urine 6-sulfatoxymelatonin acrophase compared to population normal acrophase of 03:30. Maximum difference +/- 12 hours. Urine 6-sulfatoxymelatonin measures will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Urine 6-sulfatoxymelatonin acrophase absolute timepost-treatment, 72 hours

Clock time of individual urine 6-sulfatoxymelatonin acrophase. Urine 6-sulfatoxymelatonin measures will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Urine 6-sulfatoxymelatonin acrophase change from day 1 to day 4Day 1 and post-treatment, 72 hours

Change in individual urine 6-sulfatoxymelatonin acrophase between day 1 observation and day 4 observation period (after 72 hours intervention). Urine 6-sulfatoxymelatonin measures will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Overnight sleep durationpost-treatment, 72 hours

Minutes of sleep from 22:00 to 05:59 as measured by NoxA1 portable polysomnography (PSG) device.

Overnight non-rapid eye movement stage 3 (NREM3) proportionpost-treatment, 72 hours

Proportion of Stage NREM3 sleep from 22:00 to 05:59 as measured by NoxA1 portable polysomnography device.

Overnight arousal index (continuity)post-treatment, 72 hours

Number of arousals per hour of sleep from 22:00 to 05:59 as measured by NoxA1 portable polysomnography device.

Daytime sleep durationpost-treatment, 72 hours

Minutes of sleep from 06:00 to 21:59 as measured by NoxA1 portable polysomnography device.

Daytime REM proportionpost-treatment, 72 hours

Proportion of Stage REM sleep from 06:00 to 21:59 as measured by NoxA1 portable polysomnography device.

Daytime NREM3 proportionpost-treatment, 72 hours

Proportion of Stage NREM3 sleep from 06:00 to 21:59 as measured by NoxA1 portable polysomnography device.

Daytime arousal index (continuity)post-treatment, 72 hours

Number of arousals per hour of sleep from 06:00 to 21:59 as measured by NoxA1 portable polysomnography device.

Biologic night sleep durationpost-treatment, 72 hours

Minutes of sleep during biologic night (melatonin onset to offset) as measured by NoxA1 portable polysomnography device. Biologic night determination will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Biologic night REM proportionpost-treatment, 72 hours

Proportion of Stage REM sleep during biologic night (melatonin onset to offset) as measured by NoxA1 portable polysomnography device. Biologic night determination will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Biologic night NREM3 proportionpost-treatment, 72 hours

Proportion of Stage NREM3 sleep during biologic night (melatonin onset to offset) as measured by NoxA1 portable polysomnography device. Biologic night determination will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Biologic night arousal index (continuity)post-treatment, 72 hours

Number of arousals per hour of sleep during biologic night (melatonin onset to offset) as measured by NoxA1 portable polysomnography device. Biologic night determination will be completed for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points.

Atypical sleeppost-treatment, 72 hours

Presence of atypical sleep on polysomnography recording, characterized by δ waves without cyclic organization, the absence of K-complexes and sleep spindles, and unusual sleep stage transitions.

Trial Locations

Locations (2)

Yale New Haven Hospital Medical Intensive Care Unit (YNHH MICU) at York Street

🇺🇸

New Haven, Connecticut, United States

Yale New Haven Hospital Medical Intensive Care Unit (YNHH MICU) at St Raphael's Campus

🇺🇸

New Haven, Connecticut, United States

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