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

Overview

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.

Interventions

• Other Chronobundle - light
  Bright daytime light from 09:00 to 13:00 starting on day 1. The light will be 10,000 lux at 12" and provide a minimal intensity of 1,250 lux at the angle of the eye (30" to 36" distance). The light has a temperature of 5,000 Kelvin indicating a high blue wavelength content which should maximize circadian effects (validated device Sunbox Lighting, Maryland). Following the 09:00 to 13:00 bright light, the room lights will remain on and the curtains will remain open to maximize daytime light exposu
• Other chronobundle - feeding
  For patients receiving enteral feeds, time-restricted (daytime) intermittent feeding will include 4 meals delivered at 08:00, 12:00, 16:00 and 20:00. Each meal will include one-fourth of the recommended daily tube feed volume.
• Other chronobundle - mobility
  While in the MICU, exercise/mobility sessions led by physical therapy or occupational therapy providers will occur twice daily between 09:00 and 16:00 (i.e., one additional session beyond usual care); intensity will be determined by clinical status and documented in the chart by our physical therapy service. Patients in other hospital locations (e.g., general medical ward post-MICU discharge) will receive one additional session beyond usual care via a study staff-led exercise/mobility session; i
• Other chronobundle - sleep
  Overnight sleep promotion will occur between 22:00 and 06:00 with a more restricted sleep period between 00:00 and 04:00. This will be achieved by rescheduling non-urgent care. There will be no changes to urgent care. Additionally, room lights will be dimmed, curtains drawn, and room doors closed. Television screens will be fitted with blue light-blocking filters.

Primary outcome measures

• Circadian alignment based on diurnal heart rate variation [Time frame: post-treatment, 72 hours]

Secondary outcome measures (12)

• Urine 6-sulfatoxymelatonin acrophase change from normal [Time frame: post-treatment, 72 hours]
• Urine 6-sulfatoxymelatonin acrophase absolute time [Time frame: post-treatment, 72 hours]
• Urine 6-sulfatoxymelatonin acrophase change from day 1 to day 4 [Time frame: Day 1 and post-treatment, 72 hours]
• Overnight sleep duration [Time frame: post-treatment, 72 hours]
• Overnight Rapid Eye Movement (REM) proportion [Time frame: post-treatment, 72 hours]
• Overnight non-rapid eye movement stage 3 (NREM3) proportion [Time frame: post-treatment, 72 hours]
• Overnight arousal index (continuity) [Time frame: post-treatment, 72 hours]
• Daytime sleep duration [Time frame: post-treatment, 72 hours]
• Daytime REM proportion [Time frame: post-treatment, 72 hours]
• Daytime NREM3 proportion [Time frame: post-treatment, 72 hours]
• Daytime arousal index (continuity) [Time frame: post-treatment, 72 hours]
• Biologic night sleep duration [Time frame: post-treatment, 72 hours]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 2 centers

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

Identifiers

NCT: NCT05551325 · 2000033373 · 1R01HL163659-01A1

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗