Optimizing Enteral Nutrition Regimen for Critically Ill Patients

Optimizing Enteral Nutrition: A Comparative Study of 18-Hour, 20-Hour, and 24-Hour

Clinical Trial The goal of this clinical trial is to learn whether different enteral feeding cycles (18-hour, 20-hour, or standard 24-hour continuous feeding) improve outcomes for critically ill ICU patients who need tube feeding. It will also look at tolerance, nutrition delivery, and safety.

The main questions it aims to answer are:

Do shorter feeding cycles (with fasting windows) reduce ICU length of stay?

Do they lower the risk of infections like ventilator-associated pneumonia?

How do they affect calorie delivery, blood sugar control, and gastrointestinal tolerance?

Researchers will compare:

Continuous 24-hour feeding (standard care)

20-hour feeding with a 4-hour fasting window

18-hour feeding with a 6-hour fasting window

Participants will:

Be critically ill adults in the ICU who require at least 7 days of enteral feeding

Be randomized to one of the three feeding schedules

Receive daily monitoring of calories, protein, blood sugar, and GI tolerance

Have outcomes measured, including ICU length of stay, infections, metabolic control, and feeding tolerance

Study Overview

• Status: Not yet recruiting
• Conditions: Hyperglycemia; Critical Illness; Enteral Nutrition; Ventilator Associated Pneumonia; Feeding Intolerance
• Intervention / Treatment: Behavioral: 20-Hour Cycled Enteral Nutrition with a 4-Hour Fasting Window; Behavioral: 18-Hour Cycled Enteral Nutrition with a 6-Hour Fasting Window

Detailed Description

This randomized controlled trial will compare three enteral feeding regimens in critically ill ICU patients: standard 24-hour continuous feeding, 20-hour cycled feeding with a 4-hour fasting window, and 18-hour cycled feeding with a 6-hour fasting window. The rationale is that continuous feeding may impair metabolic regulation, increase insulin requirements, and contribute to gastrointestinal intolerance, while cycled feeding could better align with circadian rhythms, support metabolic balance, and reduce complications such as ventilator-associated pneumonia.

Approximately 150 adult patients who require enteral nutrition for at least seven days will be enrolled across Hamad Medical Corporation ICUs. Participants will be randomized in a 1:1:1 ratio using block randomization through REDCap to ensure allocation concealment. All groups will receive isocaloric enteral nutrition through nasogastric or orogastric tubes, with caloric and protein targets guided by indirect calorimetry or weight-based calculations.

Feeding plans will be initiated within 24 hours of ICU admission or stabilization. Patients assigned to the 18-hour and 20-hour arms will have structured fasting periods, while the control group will receive uninterrupted feeding. Daily assessments will capture nutritional delivery, gastrointestinal tolerance, and metabolic parameters, along with safety monitoring for adverse events. Data will be collected electronically via REDCap, de-identified, and audited regularly by the Clinical Trial Unit.

The study is designed to generate high-quality evidence on whether incorporating fasting windows into feeding schedules can optimize nutrition therapy, improve tolerance, reduce ICU stays, and minimize complications. Findings are expected to inform future ICU nutrition guidelines and contribute to the global discussion on intermittent versus continuous feeding practices.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Participants must meet ALL of the following criteria to be eligible for the study:

1. Patients aged ≥ 18 years.
2. Patients expected to require enteral nutrition (EN) for ≥ 7 days.
3. Critically ill, mechanically ventilated patients in the ICU.
4. New patients initiating EN in the critical care unit.

5. Patients receiving EN via:

   • a nasogastric (NG) tube.
   • orogastric (OG) feeding tube.

Exclusion Criteria:

1. Patients with contraindications to enteral feeding or pre-existing gastrointestinal disorders, including:

   • Active GI bleeding.
   • Progressive GI disease.
   • Recent GI tract resection.
2. Indication for a special diet formula.
3. Need for a large volume of feeding (as determined by the clinical team).
4. Pre-existing hepatic failure.
5. Use of a nasojejunal tube, gastrostomy, or jejunostomy.
6. Pregnancy confirmed via β-hCG testing for women of childbearing potential.
7. Insulin-dependent diabetes mellitus.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: 24-hour continuous feeding (control); Feeding Schedule provides continuous enteral nutrition over 24 hours with no fasting window. This standard care in many ICUs serves as the baseline for comparison with two experimental cycled feeding regimens. The feeding rate is designed to evenly deliver the total daily caloric goal across the entire period.
Active Comparator: 20-hour cycled feeding (intervention); Feeding Schedule consists of enteral nutrition delivered over 20 hours, with a structured 4-hour fasting window each day. This approach aims to balance metabolic and gastrointestinal benefits while ensuring adequate daily caloric intake. Consequently, the feeding rate is increased to meet the total caloric goal within the shorter feeding period.	Behavioral: 20-Hour Cycled Enteral Nutrition with a 4-Hour Fasting Window; 20-Hour Cycled Enteral Nutrition with a 4-Hour Fasting Window (Intervention 1) Objective: To evaluate the physiological benefits of a structured daily fasting period while maintaining a conservative approach to caloric delivery.; Other Names: Group Intervention 1
Active Comparator: 18-hour cycled feeding (intervention); Feeding Schedule involves enteral nutrition over an 18-hour period while incorporating a 6-hour fasting window in each 24-hour cycle. This structure is designed to test a more intense intermittent fasting regimen, aiming to enhance physiological benefits by better aligning with circadian rhythms. The expectations include improved metabolic control, enhanced gastrointestinal motility, and reduced infection rates, with careful monitoring for reduced caloric intake risk. Consequently, the feeding rate is increased to meet daily caloric goals within the 18-hour timeframe, resulting in the most intensive feeding schedule among the three examined arms.	Behavioral: 18-Hour Cycled Enteral Nutrition with a 6-Hour Fasting Window; Feeding Schedule involves enteral nutrition over an 18-hour period while incorporating a 6-hour fasting window in each 24-hour cycle. This structure is designed to test a more intense intermittent fasting regimen, aiming to enhance physiological benefits by better aligning with circadian rhythms. The expectations include improved metabolic control, enhanced gastrointestinal motility, and reduced infection rates, with careful monitoring for reduced caloric intake risk. Consequently, the feeding rate is increased to meet daily caloric goals within the 18-hour timeframe, resulting in the most intensive feeding schedule among the three examined arms.; Other Names: Group Intervention 2

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ICU Length of Stay (LOS)	The total number of days a patient spends in the intensive care unit, calculated from the date of ICU admission to the date of discharge or transfer out of the ICU.	From the date of randomization until the date of ICU discharge or transfer, assessed up to 90 days (or until hospital discharge if it occurs earlier).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nosocomial Infection/Pneumonia Incidence	Infections acquired after 48 hours of hospital admission, specifically including Ventilator-Associated Pneumonia (VAP). Diagnosed based on CDC criteria (clinical signs, laboratory findings, and imaging).	Assessed daily from Day 3 to Day 7.
Nutritional Adequacy	The percentage of the prescribed daily caloric goal that is actually delivered to the patient.	Calculated daily from Day 1 to Day 7
Gastrointestinal Complications	Adverse events related to feeding intolerance.	Monitored daily from Day 1 to Day 7
Gastric Emptying Index	A measure of gastrointestinal motility, indicated by delayed gastric emptying. Aspirate gastric contents via a nasogastric (NG) or orogastric (OG) tube at regular intervals (every 4 hours). gastric residual volume ≤ 500 mL, persistently high GRV (>500 mL) indicates delayed emptying.	Measured every 4 hours, daily from Day 1 to Day 7.
Glycemic Control	The regulation of blood glucose levels during the enteral nutrition intervention period.Average daily blood glucose level (mmol/L or mg/dL), calculated from point-of-care testing performed throughout the day.	Daily, from Day 1 to Day 7 of the intervention.
Insulin Requirement	The total daily exogenous insulin dose required to maintain blood glucose within target range.Total insulin dose administered per 24-hour period, measured in units.	Daily, from Day 1 to Day 7 of the intervention.
Serum Creatinine level, measured in mg/dL (or µmol/L)	The change in serum creatinine concentration from baseline serves as a specific biomarker of glomerular filtration rate (GFR) and kidney function.	Measured daily from Day 1 to Day 7. The baseline value is recorded on Day 0.
Blood Urea Nitrogen (BUN) level, measured in mg/dL (or mmol/L)	Change in blood urea nitrogen concentration from baseline, as a biomarker of nitrogenous waste accumulation influenced by renal function, protein catabolism, and hydration status.	Measured daily from Day 1 to Day 7 of the intervention. The baseline value is recorded on Day 0.
Alanine Aminotransferase (ALT) level, measured in U/L	The change in serum alanine aminotransferase (ALT) concentration from baseline serves as a specific biomarker of hepatocellular injury.	Measured daily from Day 1 to Day 7 of the intervention. The baseline value is recorded on Day 0.
Aspartate Aminotransferase (AST) level, measured in U/L	Change in serum aspartate aminotransferase (AST) concentration from baseline, as a biomarker of hepatic inflammation and injury.	Measured daily from Day 1 to Day 7 of the intervention. The baseline value is recorded on Day 0.
Total Bilirubin level, measured in mg/dL (or µmol/L)	The change in serum total bilirubin concentration from baseline serves as a biomarker of hepatic excretory function and bile flow.	Measured daily from Day 1 to Day 7 of the intervention. The baseline value is recorded on Day 0.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory Marker	Level of systemic inflammation by Inflammatory Markers (e.g., CRP)	Measured daily from Day 1 to Day 7.The baseline value is recorded on Day 0.
Patient Tolerance	The ability to receive enteral nutrition without significant adverse effects.	Measured daily from Day 1 to Day 7

Collaborators and Investigators

• Sponsor: Hamad Medical Corporation

Study record dates

Study Major Dates

• Study Start (Estimated): December 30, 2025
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: September 23, 2025
• First Submitted That Met QC Criteria: November 26, 2025
• First Posted (Actual): December 8, 2025

Study Record Updates

• Last Update Posted (Actual): December 8, 2025
• Last Update Submitted That Met QC Criteria: November 26, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Gastrointestinal tolerance; Critical care nutrition; Cyclic feeding; Feeding window; Nutritional adequacy
• Additional Relevant MeSH Terms: Healthcare-Associated Pneumonia; Pathologic Processes; Disease Attributes; Metabolic Diseases; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Glucose Metabolism Disorders; Pneumonia; Cross Infection; Iatrogenic Disease; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Critical Illness; Hyperglycemia; Pneumonia, Ventilator-Associated
• Other Study ID Numbers: MRC-01-25-949

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Data will be collected and de-identified, codes will be used to cover patient identifiers such as Name, HC no., DOB. Any link between code and identifier will be deleted at the end of the data collection and anonymized data will be kept for at least 5 years after study completion. Study participation is documented using a unique study ID (e.g., "EN-001") rather than patient names. Access to identifiers is restricted to the research team and audited by the clinical trial unit (CTU) in HMC. The data that will be collected for this study will remain confidential.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No