Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness

Critical Illness Clinical Trial

— CIRCLES  

Official title:

Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness: CIRCLES Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05795881
• Other study ID #: P22.080
• Status: Recruiting
• Phase: N/A
• Start date: June 14, 2023
• Est. completion date: May 1, 2025

Study information

• Verified date: September 2023
• Source: Leiden University Medical Center
• Contact: Floor W Hiemstra, MSc
• Phone: +31 (0)71-5296713
• Email: f.w.hiemstra[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: May 1, 2025
• Est. primary completion date: February 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Circadian Rhythm
• Critical Illness
• Enteral Nutrition
• Intensive Care Unit
• Sleep

Intervention

Other:
• Cyclic daytime enteral nutrition
The allocated feeding schedule is followed from the start of enteral nutrition after ICU admission until discharge from the ICU.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (1)

Lead Sponsor	Collaborator
Leiden University Medical Center

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Amplitude of 24-h rhythm of core body temperature	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Primary	Acrophase 24-h rhythm of core body temperature	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Amplitude of 24-h rhythm of plasma melatonin levels	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Acrophase of 24-h rhythm of plasma melatonin levels	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Amplitude of 24-h rhythm in heart rate variability	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Acrophase of 24-h rhythm in heart rate variability	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Amplitude of 24-h rhythm in systolic blood pressure	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Acrophase of 24-h rhythm in systolic blood pressure	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Amplitude of 24-h rhythm in heart rate	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Acrophase of 24-h rhythm in heart rate	Determined by cosinor analysis	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Peripheral clock gene expression	Time of day-dependent difference in clock gene expression in PBMCs isolated from blood samples collected at 12 p.m. and 12 a.m.	Day 3 (12 p.m.) to day 4 (12 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Depth of sleep	Daytime (8 a.m. to 8 p.m.) to nighttime (8 p.m. to 8 a.m.) ratio of gamma to delta spectral power ratio in EEG measured with a sleep headband	Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary	Mean daily rate of hyperglycaemia/hypoglycaemia	Hypoglycaemia is defined as glucose levels < 3.5 mmol/L, hyperglycaemia is defined as glucose levels >10 mmol/L	From start of study intervention (enteral nutrition) to end of study intervention
Secondary	Mean daily glucose variability	Mean of standard deviation of glucose levels per day	From start of study intervention (enteral nutrition) to end of study intervention
Secondary	Mean daily insulin administration	Mean of number of insulin units used per day	From start of study intervention (enteral nutrition) to end of study intervention
Secondary	Mean daily caloric intake	Mean of percentage of recommended calories that patient receives per day of interest during study period	From start of study intervention (enteral nutrition) to end of study intervention
Secondary	Daily rates of gastric retention	Gastric retention is defined as gastric residual volume > 200 mL	From start of study intervention (enteral nutrition) to end of study intervention
Secondary	28-day mortality	28-day mortality	Up to 28 days
Secondary	Days on mechanical ventilation	Days on mechanical ventilation	From ICU admission to ICU discharge
Secondary	ICU length of stay	ICU length of stay	From ICU admission to ICU discharge