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Completed

NCT Number: NCT05795881

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

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.

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Key information

Conditions

Critical Illness Circadian Rhythm Disease Attributes Enteral Nutrition Intensive Care Unit Pathologic Processes Pathological Conditions, Signs and Symptoms Sleep

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Leiden University Medical Center

Leiden, 2333ZA, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Primary outcomes

  1. Amplitude of 24-h rhythm of core body temperature

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

    Determined by cosinor analysis

  2. Acrophase 24-h rhythm of core body temperature

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

    Determined by cosinor analysis

Secondary outcomes

  1. Amplitude of 24-h rhythm of plasma melatonin levels

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

    Determined by cosinor analysis

  2. Acrophase of 24-h rhythm of plasma melatonin levels

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

    Determined by cosinor analysis

  3. Amplitude of 24-h rhythm in heart rate variability

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

    Determined by cosinor analysis

  4. Acrophase of 24-h rhythm in heart rate variability

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

    Determined by cosinor analysis

  5. Amplitude of 24-h rhythm in systolic blood pressure

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

    Determined by cosinor analysis

  6. Acrophase of 24-h rhythm in systolic blood pressure

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

    Determined by cosinor analysis

  7. Amplitude of 24-h rhythm in heart rate

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

    Determined by cosinor analysis

  8. Acrophase of 24-h rhythm in heart rate

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

    Determined by cosinor analysis

  9. Peripheral clock gene expression

    Time frame: Day 3 (12 p.m.) to day 4 (12 a.m.) after start of the study intervention (= start of enteral nutrition)

    Time of day-dependent difference in clock gene expression in PBMCs isolated from blood samples collected at 12 p.m. and 12 a.m.

  10. Depth of sleep

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

    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

  11. Mean daily rate of hyperglycaemia/hypoglycaemia

    Time frame: From start of study intervention (enteral nutrition) to end of study intervention

    Hypoglycaemia is defined as glucose levels < 3.5 mmol/L, hyperglycaemia is defined as glucose levels >10 mmol/L

  12. Mean daily glucose variability

    Time frame: From start of study intervention (enteral nutrition) to end of study intervention

    Mean of standard deviation of glucose levels per day

  13. Mean daily insulin administration

    Time frame: From start of study intervention (enteral nutrition) to end of study intervention

    Mean of number of insulin units used per day

  14. Mean daily caloric intake

    Time frame: From start of study intervention (enteral nutrition) to end of study intervention

    Mean of percentage of recommended calories that patient receives per day of interest during study period

  15. Daily rates of gastric retention

    Time frame: From start of study intervention (enteral nutrition) to end of study intervention

    Gastric retention is defined as gastric residual volume > 200 mL

  16. 28-day mortality

    Time frame: Up to 28 days

    28-day mortality

  17. Days on mechanical ventilation

    Time frame: From ICU admission to ICU discharge

    Days on mechanical ventilation

  18. ICU length of stay

    Time frame: From ICU admission to ICU discharge

    ICU length of stay

Sponsors and collaborators

Lead sponsor

Leiden University Medical Center

Other

Registry information

Official study title

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

Acronym: CIRCLES

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Apr 3, 2023
Registry last updated
Mar 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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