Clinical trial NCT05551325: Reestablishing Sleep and Circadian Alignment in Medical Intensive Care Unit (MICU) Patients Via a Mechanistic RCT of an Sleep Chronobundle
Official title: Reestablishing Sleep and Circadian Alignment in Medically Critically Ill Patients Via a Mechanistic Randomized Controlled Trial (RCT) of an Intensive Care Unit (ICU) Sleep Chronobundle
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Critical Illness
Sleep Deprivation
Circadian Rhythm Sleep Disorder, Unspecified
Keywords: critical illness
sleep deficiency
circadian misalignment
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2022-09-22
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 1:1 randomization of patients to control or intervention
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion:

* Critically ill patients admitted to the MICU who require mechanical ventilation, noninvasive ventilation, high flow nasal cannula, or vasopressor support and who remain on qualifying support as of 09:00 on study randomization day. Randomization will occur on the second or third calendar day following MICU admission. MICU admission must have occurred within 24 hours of hospital admission.
* Age greater than or equal to 18 years old.

Exclusion:

* Not expected to remain in the MICU for at least 48 hours post-randomization.
* Imminently dying or with a hospice status.
* At significant risk for pre-existing circadian abnormalities including: (1) severe chronic brain injury (injury greater than 30 days ago resulting in the inability to live independently); (2) acute brain injury of any severity that is reasonably expected to impact the central circadian clock (e.g., cardiac arrest); (3) documented circadian disorder (\<1% population) or blind/disease of the optic nerve; (4) current or recent (last 1 year) shiftwork; and (5) homelessness, incarceration, or institutionalization.
* At elevated risk of aspiration due to structural or functional abnormality of the gastrointestinal tract OR fed via enteral nutrition (e.g., "tube feeds") prior to ICU admission.
* Admitted to the ICU for treatment of diabetic ketoacidosis or hyperosmolar state; this diagnosis will be established via review of the medical record for a description of diabetes in the past medical history or the presence of diabetes medication on the confirmed home medication list AND hyperglycemia attributed to diabetic ketoacidosis or diabetic hyperosmolar state by the admitting care team in their written assessment of the patient.
* Having a history of hypoglycemia without documented full neurological recovery; this diagnosis will be established via review of the patient's past medical history in the medical record;
* Having a history suggesting an abnormally high risk of suffering hypoglycemia (e.g., known insulin secreting tumor, history of unexplained or recurrent hypoglycemia or fulminant hepatic failure); this diagnosis will be established via review of the patient's past medical history in the medical record.
* Admitted due to complications of a suicide attempt.
* Admitted due to an acute drug overdose or active alcohol withdrawal.
* Positive for SARS-CoV.

Urine 6-sulfatoxymelatonin measures will be considered for all patients who make sufficient urine and have an appropriate bladder catheter in place during the indicated time points. However, we will exclude patients from urine measures if they have a history or positive test for any known disease or illness that would categorize biological samples as BSL3 or higher. This includes HIV, West Nile virus, Monkeypox, and Mycobacterium tuberculosis (TB).

Note: Patients who leave the MICU within 24 hours of randomization are excluded from further study activities. Patients who leave the MICU between 24 and 48 hours post-randomization continue all study activities but will not be included in the primary analysis. Patients who remain in the MICU for at least 48 hours post-randomization will continue all study activities and be included in the primary analysis.

Primary outcomes:
measure: Circadian alignment based on diurnal heart rate variation
timeFrame: post-treatment, 72 hours
Secondary outcomes:
measure: Urine 6-sulfatoxymelatonin acrophase change from normal
timeFrame: post-treatment, 72 hours
measure: Urine 6-sulfatoxymelatonin acrophase absolute time
timeFrame: post-treatment, 72 hours
measure: Urine 6-sulfatoxymelatonin acrophase change from day 1 to day 4
timeFrame: Day 1 and post-treatment, 72 hours
measure: Overnight sleep duration
timeFrame: post-treatment, 72 hours
measure: Overnight Rapid Eye Movement (REM) proportion
timeFrame: post-treatment, 72 hours
measure: Overnight non-rapid eye movement stage 3 (NREM3) proportion
timeFrame: post-treatment, 72 hours
measure: Overnight arousal index (continuity)
timeFrame: post-treatment, 72 hours
measure: Daytime sleep duration
timeFrame: post-treatment, 72 hours
measure: Daytime REM proportion
timeFrame: post-treatment, 72 hours
measure: Daytime NREM3 proportion
timeFrame: post-treatment, 72 hours
measure: Daytime arousal index (continuity)
timeFrame: post-treatment, 72 hours
measure: Biologic night sleep duration
timeFrame: post-treatment, 72 hours
measure: Biologic night REM proportion
timeFrame: post-treatment, 72 hours
measure: Biologic night NREM3 proportion
timeFrame: post-treatment, 72 hours
measure: Biologic night arousal index (continuity)
timeFrame: post-treatment, 72 hours
measure: Atypical sleep
timeFrame: post-treatment, 72 hours
measure: Glucose tolerance
timeFrame: post-treatment, 72 hours
Other outcomes:
measure: Exploratory - Days without Delirium or Coma
timeFrame: post-treatment, 14 days post randomization
measure: Exploratory - Ventilator Free Days
timeFrame: post-treatment, 28 days post randomization
measure: Exploratory - Time to ICU Discharge
timeFrame: post-treatment
measure: Exploratory - Time to Hospital Discharge
timeFrame: post-treatment
measure: Exploratory - Mortality
timeFrame: post-treatment, 30 days post-randomization
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital Medical Intensive Care Unit (YNHH MICU) at St Raphael's Campus
state: Connecticut
city: New Haven
country: United States
facility: Yale New Haven Hospital Medical Intensive Care Unit (YNHH MICU) at York Street
state: Connecticut
Study officials:
affiliation: Yale University
name: Melissa P Knauert, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: