Back to resultsEffect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness (CIRCLES)
Primary Purpose
Critical Illness, Intensive Care Unit, Circadian Rhythm
Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Cyclic daytime enteral nutrition
Sponsored by
About this trial
This is an interventional treatment trial for Critical Illness focused on measuring Randomized Controlled Trial
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
Sites / Locations
- Leiden University Medical CenterRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
No Intervention
Experimental
Arm Label
Control group
Intervention group
Arm Description
continuous enteral nutrition: 24 hours a day (standard of care)
cyclic daytime enteral nutrition: between 8 a.m. and 8 p.m. (same amount of nutrition as control group)
Outcomes
Primary Outcome Measures
Amplitude of 24-h rhythm of core body temperature
Determined by cosinor analysis
Acrophase 24-h rhythm of core body temperature
Determined by cosinor analysis
Secondary Outcome Measures
Amplitude of 24-h rhythm of plasma melatonin levels
Determined by cosinor analysis
Acrophase of 24-h rhythm of plasma melatonin levels
Determined by cosinor analysis
Amplitude of 24-h rhythm in heart rate variability
Determined by cosinor analysis
Acrophase of 24-h rhythm in heart rate variability
Determined by cosinor analysis
Amplitude of 24-h rhythm in systolic blood pressure
Determined by cosinor analysis
Acrophase of 24-h rhythm in systolic blood pressure
Determined by cosinor analysis
Amplitude of 24-h rhythm in heart rate
Determined by cosinor analysis
Acrophase of 24-h rhythm in heart rate
Determined by cosinor analysis
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.
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
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
Mean daily glucose variability
Mean of standard deviation of glucose levels per day
Mean daily insulin administration
Mean of number of insulin units used per day
Mean daily caloric intake
Mean of percentage of recommended calories that patient receives per day of interest during study period
Daily rates of gastric retention
Gastric retention is defined as gastric residual volume > 200 mL
28-day mortality
28-day mortality
Days on mechanical ventilation
Days on mechanical ventilation
ICU length of stay
ICU length of stay
Full Information
NCT ID
NCT05795881
First Posted
March 6, 2023
Last Updated
September 6, 2023
Sponsor
Leiden University Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT05795881
Brief Title
Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness
Acronym
CIRCLES
Official Title
Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness: CIRCLES Study
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2023 (Actual)
Primary Completion Date
February 1, 2025 (Anticipated)
Study Completion Date
May 1, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Critical Illness, Intensive Care Unit, Circadian Rhythm, Sleep, Enteral Nutrition
Keywords
Randomized Controlled Trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Investigator-Initiated Randomized Controlled Trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Control group
Arm Type
No Intervention
Arm Description
continuous enteral nutrition: 24 hours a day (standard of care)
Arm Title
Intervention group
Arm Type
Experimental
Arm Description
cyclic daytime enteral nutrition: between 8 a.m. and 8 p.m. (same amount of nutrition as control group)
Intervention Type
Other
Intervention Name(s)
Cyclic daytime enteral nutrition
Intervention Description
The allocated feeding schedule is followed from the start of enteral nutrition after ICU admission until discharge from the ICU.
Primary Outcome Measure Information:
Title
Amplitude of 24-h rhythm of core body temperature
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Acrophase 24-h rhythm of core body temperature
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Secondary Outcome Measure Information:
Title
Amplitude of 24-h rhythm of plasma melatonin levels
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Acrophase of 24-h rhythm of plasma melatonin levels
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Amplitude of 24-h rhythm in heart rate variability
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Acrophase of 24-h rhythm in heart rate variability
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Amplitude of 24-h rhythm in systolic blood pressure
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Acrophase of 24-h rhythm in systolic blood pressure
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Amplitude of 24-h rhythm in heart rate
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Acrophase of 24-h rhythm in heart rate
Description
Determined by cosinor analysis
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Peripheral clock gene expression
Description
Time of day-dependent difference in clock gene expression in PBMCs isolated from blood samples collected at 12 p.m. and 12 a.m.
Time Frame
Day 3 (12 p.m.) to day 4 (12 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Depth of sleep
Description
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
Time Frame
Day 3 (8 a.m.) to day 4 (8 a.m.) after start of the study intervention (= start of enteral nutrition)
Title
Mean daily rate of hyperglycaemia/hypoglycaemia
Description
Hypoglycaemia is defined as glucose levels < 3.5 mmol/L, hyperglycaemia is defined as glucose levels >10 mmol/L
Time Frame
From start of study intervention (enteral nutrition) to end of study intervention
Title
Mean daily glucose variability
Description
Mean of standard deviation of glucose levels per day
Time Frame
From start of study intervention (enteral nutrition) to end of study intervention
Title
Mean daily insulin administration
Description
Mean of number of insulin units used per day
Time Frame
From start of study intervention (enteral nutrition) to end of study intervention
Title
Mean daily caloric intake
Description
Mean of percentage of recommended calories that patient receives per day of interest during study period
Time Frame
From start of study intervention (enteral nutrition) to end of study intervention
Title
Daily rates of gastric retention
Description
Gastric retention is defined as gastric residual volume > 200 mL
Time Frame
From start of study intervention (enteral nutrition) to end of study intervention
Title
28-day mortality
Description
28-day mortality
Time Frame
Up to 28 days
Title
Days on mechanical ventilation
Description
Days on mechanical ventilation
Time Frame
From ICU admission to ICU discharge
Title
ICU length of stay
Description
ICU length of stay
Time Frame
From ICU admission to ICU discharge
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Floor W Hiemstra, MSc
Phone
+31 (0)71-5296713
Email
f.w.hiemstra@lumc.nl
First Name & Middle Initial & Last Name or Official Title & Degree
L. Kervezee, PhD
Email
l.kervezee@lumc.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David J van Westerloo, PhD, MD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333ZA
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
David van Westerloo, MD PhD
Email
d.j.van_westerloo@lumc.nl
First Name & Middle Initial & Last Name & Degree
Floor Hiemstra, MSc
Email
f.w.hiemstra@lumc.nl
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Immediately following publication, the individual participant data that underlie the results reported in the published article will be shared after deidentificiation. The data will be shared upon request with researchers who wish to access the data for any purpose.
IPD Sharing Time Frame
The data will be available immediately following publication.
IPD Sharing Access Criteria
to be announced
Citations:
PubMed Identifier
35797531
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.
Results Reference
background
Learn more about this trial
Effect of Continuous Versus Cyclic Daytime Enteral Nutrition on Circadian Rhythms in Critical Illness
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