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

• ClinicalTrials.gov Identifier: NCT04737200
• Recruitment Status: Recruiting
• First Posted: February 3, 2021
• Last Update Posted: March 14, 2023
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Hassan Dashti, Massachusetts General Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Feeding Patterns; Sleep; Glucose Intolerance	Dietary Supplement: Time-of-day of enteral nutrition provision (daytime first); Dietary Supplement: Time-of-day of enteral nutrition provision (nighttime first)	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Supportive Care
• Official Title: The Impact of Overnight Nutrition Support on Sleep and Circadian Rhythm Disruption in the ICU
• Actual Study Start Date: February 8, 2022
• Estimated Primary Completion Date: December 31, 2025
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Nighttime cycled enteral feeds first; 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); Enteral nutrition (tube feeds) will be provided during the nighttime followed by daytime.
Experimental: Daytime cycled enteral feeds first; 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); Enteral nutrition (tube feeds) will be provided during the daytime followed by nighttime.

Outcome Measures

Primary Outcome Measures :

1. Sleep fragmentation [ Time Frame: Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. ]
   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.
2. Circadian rhythms amplitude [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Amplitude is defined as peak-to-nadir difference in rhythms estimated from body temperature and actigraphy.

Secondary Outcome Measures :

1. Sleep arousals [ Time Frame: Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. ]
   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.
2. Total sleep time [ Time Frame: Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. ]
   Measure of sleep duration and assessed objectively through EEG measures.
3. Duration of sleep stages [ Time Frame: Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. ]
   Duration of the following sleep stages will be estimated: N1, N2, N3, REM sleep. Sleep stages will be assessed objectively through EEG measures.
4. Sleep midpoint [ Time Frame: Approximately 12 hours. Estimated from nighttime sleep following daytime cycled enteral feeds and during nighttime cycled enteral feeds. ]
   Sleep midpoint is defined as the midpoint between start and end of sleep episode. Sleep midpoint will be determined objectively from EEG measures.
5. Acrophase [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Acrophase is defined as the time of peak activity.
6. Midpoint of least-active 5h timing [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Measure of sleep timing as determined from actigraphy.
7. Midpoint of most-active 10h timing [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Measure of sleep timing as determined from actigraphy.
8. Inactivity duration [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Duration of inactivity outside of sleep episode as determined from actigraphy.
9. 12 hours average systolic and diastolic blood pressure [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
   Continuously measured using ECG. Systolic and diastolic blood pressure will be averaged during each 12-hour cycled feed.
10. 12 hours average glucose [ Time Frame: Estimated from data collected 12 hours prior to and the 12 hours during daytime cycled and nighttime cycled enteral feeds. ]
    Continuously measured using continuous glucose sensors. Blood glucose will be averaged during each 12-hour cycled feed.
11. C-reactive protein [ Time Frame: Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. ]
    The inflammatory biomarker C-reactive protein will be measured from serum.
12. Interleukin-6 [ Time Frame: Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. ]
    The inflammatory biomarker Interleukin-6 will be measured from serum.
13. Tumor necrosis factor α [ Time Frame: Blood draw scheduled at 8 am and 8 pm on days on daytime cycled and nighttime cycled enteral feeds. ]
    The inflammatory biomarker Tumor necrosis factor α will be measured from serum.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Hassan S Dashti, Ph.D., R.D.; 617-643-7167; chrononutrition@mgh.harvard.edu

Contact: Richa Saxena, Ph.D.; rsaxena@partners.org

Locations

United States, Massachusetts

Massachusetts General Hospital; Recruiting

Boston, Massachusetts, United States, 02114

Contact: Hassan S Dashti

Sponsors and Collaborators

Massachusetts General Hospital

Investigators

• Principal Investigator: Hassan S Dashti, Ph.D., R.D.; Massachusetts General Hospital

More Information

• Responsible Party: Hassan Dashti, Principal Investigator, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT04737200
• Other Study ID Numbers: 2020P003989
• First Posted: February 3, 2021
• Last Update Posted: March 14, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Hassan Dashti, Massachusetts General Hospital:

Enteral Nutrition; Chrononutrition; Intensive Care Unit; Chronobiology; Nutrition Support; Sleep

Additional relevant MeSH terms:

Glucose Intolerance; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases