The Impact of Overnight Nutrition Support on Sleep and Circadian Rhythm Disruption in the ICU

Study Overview
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Brief Summary
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The purpose of this study is to determine whether modifying the timing of nutrition support from overnight to daytime enhances sleep quality, preserves circadian rhythms, and improves overall inflammation and cardiometabolic profiles in postoperative patients in the cardiac surgical ICU on enteral nutrition.

Detailed Description
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Intensive care unit (ICU) environments do not support sleep or preserve circadian rhythms of postoperative critically ill patients. Among the contributing factors is the common practice of administering nutrition support through feeding tubes overnight. The overall objective of the study is to examine a novel dimension of clinical nutrition by determining whether enhancing sleep quality and preserving robust circadian rhythms through daytime instead of overnight feeds will attenuate inflammation and improve cardiometabolic profiles of postoperative cardiac ICU patients on nutrition support. The investigators hypothesize that overnight nutrition support results in fragmented sleep and blunted circadian rhythms and thus represent a modifiable mechanism exacerbating inflammation and cardiometabolic derangements in postoperative cardiac patients. Results of this study will help in the development of evidence-based, cost-efficient, and effective enteral nutrition timing countermeasures against fragmented sleep, disrupted circadian rhythms, inflammation and cardiometabolic derangements and potentially modify the current widespread practice of overnight nutrition likely affecting 250,000 hospital admissions annually in the United States.

Official Title
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The Impact of Overnight Nutrition Support on Sleep and Circadian Rhythm Disruption in the ICU

Conditions
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Feeding Patterns, Sleep, Glucose Intolerance

Intervention / Treatment
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* Dietary Supplement: Time-of-day of enteral nutrition provision (daytime first)
* Dietary Supplement: Time-of-day of enteral nutrition provision (nighttime first)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult male or non-pregnant female volunteers (age 18+) Scheduled for a cardiac surgical procedure with planned post-operative admission to the ICU for >48 hours Able and willing to give consent and comply with study procedures Exclusion Criteria: Blind, deaf or unable to speak English Women who are pregnant or nursing Contraindications to safe use enteral nutrition, including gastrointestinal obstruction Personal history of intestinal malabsorption, gallbladder disease or pancreatitis Dietary restrictions precluding enteral feeds Renal and liver failure requiring dialysis or Child-Pugh score > 7 Chronic therapy with benzodiazepines and/or antipsychotics Severe deficit due to structural or anoxic brain damage With skin condition that precludes wearing sensors

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nighttime cycled enteral feeds first<br>Patients will start nighttime cycled enteral feeds first for 12 hours. Following a 24-hour washout period, patients will then start daytime cycled enteral feeds for 12 hours. | Dietary Supplement: Time-of-day of enteral nutrition provision (nighttime first)<br>* Enteral nutrition (tube feeds) will be provided during the nighttime followed by daytime.<br>|
| Experimental: Daytime cycled enteral feeds first<br>Patients will start daytime cycled enteral feeds first for 12 hours. Following a 24-hour washout period, patients will then start nighttime cycled enteral feeds for 12 hours. | Dietary Supplement: Time-of-day of enteral nutrition provision (daytime first)<br>* Enteral nutrition (tube feeds) will be provided during the daytime followed by nighttime.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep fragmentation | Sleep fragmentation is defined as the number of shifts from deeper (N2, N3, REM) to lighter (W or N1) sleep stages by hours of sleep. Sleep fragmentation will be assessed objectively through EEG measures. | Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. | 
| Circadian rhythms amplitude | Amplitude is defined as peak-to-nadir difference in rhythms estimated from body temperature and actigraphy. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep arousals | Sleep arousals is defined as n shifts from N1, N2, N3, REM to wake divided by hours of sleep. Sleep arousals will be assessed objectively through EEG measures. | Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. | 
| Total sleep time | Measure of sleep duration and assessed objectively through EEG measures. | Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. | 
| Duration of sleep stages | Duration of the following sleep stages will be estimated: N1, N2, N3, REM sleep. Sleep stages will be assessed objectively through EEG measures. | Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. | 
| Sleep midpoint | Sleep midpoint is defined as the midpoint between start and end of sleep episode. Sleep midpoint will be determined objectively from EEG measures. | Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. | 
| Acrophase | Acrophase is defined as the time of peak activity. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| Midpoint of least-active 5h timing | Measure of sleep timing as determined from actigraphy. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| Midpoint of most-active 10h timing | Measure of sleep timing as determined from actigraphy. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| Inactivity duration | Duration of inactivity outside of sleep episode as determined from actigraphy. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| 12 hours average systolic and diastolic blood pressure | Continuously measured using ECG. Systolic and diastolic blood pressure will be averaged during each 12-hour cycled feed. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| 12 hours average glucose | Continuously measured using continuous glucose sensors. Blood glucose will be averaged during each 12-hour cycled feed. | Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. | 
| C-reactive protein | The inflammatory biomarker C-reactive protein will be measured from serum. | Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. | 
| Interleukin-6 | The inflammatory biomarker Interleukin-6 will be measured from serum. | Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. | 
| Tumor necrosis factor α | The inflammatory biomarker Tumor necrosis factor α will be measured from serum. | Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enteral Nutrition, Chrononutrition, Intensive Care Unit, Chronobiology, Nutrition Support, Sleep