Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness
- Conditions
- Circadian RhythmEnteral NutritionCritical IllnessIntensive Care UnitSleep
- Interventions
- Other: Cyclic daytime enteral nutrition
- Registration Number
- NCT05795881
- Lead Sponsor
- Leiden University Medical Center
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 60
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention group Cyclic daytime enteral nutrition cyclic daytime enteral nutrition: between 8 a.m. and 8 p.m. (same amount of nutrition as control group)
- Primary Outcome Measures
Name Time Method Amplitude of 24-h rhythm of core body temperature 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
Acrophase 24-h rhythm of core body temperature 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 Outcome Measures
Name Time Method Acrophase of 24-h rhythm in heart rate 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
Days on mechanical ventilation From ICU admission to ICU discharge Days on mechanical ventilation
ICU length of stay From ICU admission to ICU discharge ICU length of stay
Daily rates of gastric retention From start of study intervention (enteral nutrition) to end of study intervention Gastric retention is defined as gastric residual volume \> 200 mL
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) Determined by cosinor analysis
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) Determined by cosinor analysis
Amplitude of 24-h rhythm in heart rate 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
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) Determined by cosinor analysis
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) Determined by cosinor analysis
Peripheral clock gene expression 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.
Mean daily rate of hyperglycaemia/hypoglycaemia 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
Mean daily glucose variability From start of study intervention (enteral nutrition) to end of study intervention Mean of standard deviation of glucose levels per day
Mean daily insulin administration From start of study intervention (enteral nutrition) to end of study intervention Mean of number of insulin units used per day
Mean daily caloric intake 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
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) Determined by cosinor analysis
Acrophase 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) Determined by cosinor analysis
Depth of sleep 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
28-day mortality Up to 28 days 28-day mortality
Trial Locations
- Locations (1)
Leiden University Medical Center
🇳🇱Leiden, Netherlands