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

NCT05795881 | Completed DMC

• 1 other identifier: P22.080
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Randomized Controlled Trial

Outcome Measures

Primary Outcomes (2)

• 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)

• 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 Outcomes (18)

• Amplitude of 24-h rhythm of plasma melatonin levels

  Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)

• Acrophase of 24-h rhythm of plasma melatonin levels

  Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)

• Amplitude of 24-h rhythm in heart rate variability

  Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)

• Acrophase of 24-h rhythm in heart rate variability

  Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)

• Amplitude of 24-h rhythm in systolic blood pressure

  Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)

Study Arms (2)

Control group

NO INTERVENTION

continuous enteral nutrition: 24 hours a day (standard of care)

Intervention group

EXPERIMENTAL

cyclic daytime enteral nutrition: between 8 a.m. and 8 p.m. (same amount of nutrition as control group)

Other: Cyclic daytime enteral nutrition

Interventions

Cyclic daytime enteral nutrition OTHER

The allocated feeding schedule is followed from the start of enteral nutrition after ICU admission until discharge from the ICU.

Intervention group

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• Receiving parenteral nutrition
• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333ZA, Netherlands

Location

Related Publications (2)

• 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.

  PMID: 35797531 BACKGROUND

• Hiemstra FW, van Gent MF, de Jonge E, van Westerloo DJ, Kervezee L. Effect of cyclic daytime versus continuous enteral nutrition on circadian rhythms in critical illness (CIRCLES): Study protocol for a randomized controlled trial. Contemp Clin Trials. 2025 Jul;154:107927. doi: 10.1016/j.cct.2025.107927. Epub 2025 Apr 27.

  PMID: 40300711 DERIVED

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• David J van Westerloo, PhD, MD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD PhD

Model Details: Investigator-Initiated Randomized Controlled Trial

Study Record Dates

• First Submitted: March 6, 2023
• First Posted: April 3, 2023
• Study Start: June 14, 2023
• Primary Completion: March 15, 2025
• Study Completion: March 15, 2025
• Last Updated: March 20, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be available immediately following publication.
• Access Criteria: to be announced

Locations

NL (1)