Clinical trial NCT05795881: Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness
Official title: Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness: CIRCLES Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Critical Illness
Intensive Care Unit
Circadian Rhythm
Sleep
Enteral Nutrition
Keywords: Randomized Controlled Trial
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
First posted: 2023-04-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator-Initiated Randomized Controlled Trial
Primary purpose: TREATMENT

Brief summary: Disruption of circadian rhythms is frequently observed in patients in the intensive care unit (ICU) and is associated with worse clinical outcomes. The ICU environment presents weak and conflicting timing cues to the circadian clock, including continuous enteral nutrition. The goal of this clinical trial is to evaluate the effect of timing of enteral nutrition on the circadian rhythm in critically ill patients. Patients admitted to the intensive care unit will be allocated to receive either continuous or cyclic daytime (8am to 8 pm) enteral feeding. Differences in circadian rhythms will be assessed by 24h patterns in core body temperature, heart rate variability, melatonin and peripheral clock gene expression. Secondary outcomes include depth of sleep, glucose variability and incidence of feeding intolerance. This study is expected to contribute to the optimalisation of circadian rhythms in the ICU.


Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years old
* Receiving of or intention to start enteral nutrition via nasogastric or nasoduodenal tube
* Arterial line
* Expected duration of ICU admission \> 48 hours

Exclusion Criteria:

* Receiving parenteral nutrition
* Prior night-time (20.00h - 8.00h) enteral tube feeding within the same hospitalization before study inclusion
* Readmission to ICU with prior study inclusion
* Chronic enteral tube feeding prior to current admission
* Presence of one or more contraindications of enteral feeding and/or at significant risk for gastrointestinal tolerance according to standard protocol (including but not limited to gastrointestinal haemorrhage, intestinal ischemia or necrosis, impaired digestive tract integrity due to obstruction or perforation, gastrectomy, enterectomy, history of gastroparesis or oesophageal dysmotility or expected surgery within 24 hours)
* Patients with glycaemic emergency (including but not limited to hyperglycaemic hyperosmolar nonketotic coma, diabetic ketoacidosis, severe hypoglycaemia resulting in ICU admission) or patients controlling their glucose levels and insulin dosing via continuous glucose monitoring
* Expected death within 24 hours
* Do-not-resuscitate (DNR) order
* Treatment with extracorporeal membrane oxygenation
* Severe neurological damage (significant neurological abnormalities such as bleeding, ischemia, neurotrauma or severe encephalopathy with Glasgow Coma Scale ≤ 8)
* Suspected or confirmed pregnancy

Primary outcomes:
measure: Amplitude of 24-h rhythm of core body temperature
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Acrophase 24-h rhythm of core body temperature
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary outcomes:
measure: Amplitude of 24-h rhythm of plasma melatonin levels
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Acrophase of 24-h rhythm of plasma melatonin levels
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Amplitude of 24-h rhythm in heart rate variability
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Acrophase of 24-h rhythm in heart rate variability
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Amplitude of 24-h rhythm in systolic blood pressure
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Acrophase of 24-h rhythm in systolic blood pressure
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Amplitude of 24-h rhythm in heart rate
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Acrophase of 24-h rhythm in heart rate
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Peripheral clock gene expression
timeFrame: Day 3 (12 p.m.) to day 4 (12 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Depth of sleep
timeFrame: Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
measure: Mean daily rate of hyperglycaemia/hypoglycaemia
timeFrame: From start of study intervention (enteral nutrition) to end of study intervention
measure: Mean daily glucose variability
timeFrame: From start of study intervention (enteral nutrition) to end of study intervention
measure: Mean daily insulin administration
timeFrame: From start of study intervention (enteral nutrition) to end of study intervention
measure: Mean daily caloric intake
timeFrame: From start of study intervention (enteral nutrition) to end of study intervention
measure: Daily rates of gastric retention
timeFrame: From start of study intervention (enteral nutrition) to end of study intervention
measure: 28-day mortality
timeFrame: Up to 28 days
measure: Days on mechanical ventilation
timeFrame: From ICU admission to ICU discharge
measure: ICU length of stay
timeFrame: From ICU admission to ICU discharge
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: David J van Westerloo, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kouw IWK, Heilbronn LK, van Zanten ARH. Intermittent feeding and circadian rhythm in critical illness. Curr Opin Crit Care. 2022 Aug 1;28(4):381-388. doi: 10.1097/MCC.0000000000000960. Epub 2022 Jul 5.