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

NCT05551325 | Recruiting DMC

• 2 other identifiers: 20000333731R01HL163659-01A1
• Study Type: interventional
• Target: 160
• Locations: 1 country
• Sites: 2

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.

Conditions

Critical Illness; Sleep Deprivation; Circadian Rhythm Sleep Disorder, Unspecified

Keywords

critical illness; sleep deficiency; circadian misalignment

Outcome Measures

Primary Outcomes (1)

• Circadian alignment based on diurnal heart rate variation

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

  post-treatment, 72 hours

Secondary Outcomes (17)

• Urine 6-sulfatoxymelatonin acrophase change from normal

  post-treatment, 72 hours

• Urine 6-sulfatoxymelatonin acrophase absolute time

  post-treatment, 72 hours

• Urine 6-sulfatoxymelatonin acrophase change from day 1 to day 4

  Day 1 and post-treatment, 72 hours

• Overnight sleep duration

  post-treatment, 72 hours

• Overnight Rapid Eye Movement (REM) proportion

  post-treatment, 72 hours

Other Outcomes (5)

• Exploratory - Days without Delirium or Coma

  post-treatment, 14 days post randomization

• Exploratory - Ventilator Free Days

  post-treatment, 28 days post randomization

• Exploratory - Time to ICU Discharge

  post-treatment

Study Arms (2)

Control

NO INTERVENTION

Usual ICU care.

Chronobundle

EXPERIMENTAL

The chronobundle will include bright daytime light, time-restricted intermittent feeding, enhanced exercise/mobility, and overnight sleep promotion.

Other: Chronobundle - light; Other: chronobundle - feeding; Other: chronobundle - mobility; Other: chronobundle - sleep

Interventions

Chronobundle - light OTHER

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 exposure while not decreasing bright light tolerance.

Chronobundle

chronobundle - feeding OTHER

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.

Chronobundle

chronobundle - mobility OTHER

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; intensity will be determined by clinical status.

Chronobundle

chronobundle - sleep OTHER

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.

Chronobundle

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (2)

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

New Haven, Connecticut, 06520, United States

RECRUITING

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

New Haven, Connecticut, 06520, United States

RECRUITING

MeSH Terms

Conditions

Critical Illness; Sleep Deprivation; Sleep Disorders, Circadian Rhythm

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Mental Disorders; Chronobiology Disorders; Occupational Diseases

Study Officials

• Melissa P Knauert, MD, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Melissa P Knauert, MD, PhD

CONTACT

203-785-4163; melissa.knauert@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the intervention participants, care providers, and investigators will be able to ascertain group assignment. Primary and secondary outcome assessors of urine 6-sulfatoxymelatonin levels, sleep scoring, and glucose levels via continuous glucose monitoring will be masked from group assignment. Exploratory outcome assessors will be able to ascertain group assignment as they will be at the patient's bedside or in the medical record during the process of recording outcomes.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 1:1 randomization of patients to control or intervention

Study Record Dates

• First Submitted: September 19, 2022
• First Posted: September 22, 2022
• Study Start: May 13, 2024
• Primary Completion (Estimated): June 29, 2028
• Study Completion (Estimated): June 29, 2028
• Last Updated: November 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)