The goal of this clinical trial is to determine whether intermittent enteral feeding positively influences circadian rhythms in critically ill patients in intensive care units (ICUs). The main research questions are: 1. Does intermittent feeding improve circadian rhythms in ICU patients? 2. How does intermittent feeding affect metabolic markers and recovery outcomes? Researchers will compare intermittent feeding to continuous feeding, the current standard method, to assess its impact on circadian stability and patient health. Participants will: 1. Receive intermittent enteral feeding or continuous enteral feeding for at least 10 days 2. Undergo blood sample collection at three time points daily (morning, afternoon, midnight) to analyze circadian gene expression and metabolic markers 3. Have their clinical condition, nutrition status, and recovery progress monitored throughout the study
Circadian rhythms regulate various physiological processes over a 24-hour cycle, including sleep-wake patterns, digestion, blood pressure, and hormone secretion. These rhythms are primarily controlled by the suprachiasmatic nucleus in the hypothalamus and influenced by environmental cues (zeitgebers), such as light exposure and meal timing. Critically ill patients often experience circadian rhythm disruptions due to prolonged artificial lighting, sleep disturbances, and continuous feeding, which may negatively impact metabolic health, immune function, and recovery. Given the significance of meal timing in circadian regulation, intermittent feeding might serve as a therapeutic strategy to restore circadian balance in ICU patients. This study is a prospective, randomized controlled trial and will be conducted at Ankara Training and Research Hospital's Anesthesia Intensive Care Unit. Ethical approval for the study has been obtained from Ankara Training and Research Hospital with decision number E-93471371-514.99-226714167. Patients will be randomly assigned to one of two groups: * Intermittent Feeding Group - enteral nutrition will be provided at scheduled intervals (4-6 times daily) for 20-60 minutes per session, aligning with circadian cycles. Light exposure will also be adjusted, ensuring darkness during night hours. * Continuous Feeding Group - patients will receive standard continuous enteral nutrition, without specific adjustments for circadian rhythms. Blood samples will be collected on Day 1 and Day 7 at 08:00, 16:00, and 00:00 to analyze Brain and muscle aryl hydrocarbon receptor nuclear antigen-1 (BMAL1), Cyrptochrome 1 (CRY1), and Period 2 (PER2) gene expression and biochemical markers. No invasive procedures will be performed beyond routine ICU care. Patients' medical history, nutritional status, and clinical parameters will be recorded by using Acute Physiology and Chronic Health Evaluation II (APACHE II) Score, Sequential Organ Failure Assessment (SOFA) Score, Nutrition Risk in Critically ill (NUTRIC) Score and Global Leadership Initiative on Malnutrition (GLIM) Criteria.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
SINGLE
Enrollment
24
Feeding Frequency: Enteral nutrition will be provided every 4 to 6 hours via nasogastric tube. Feeding Volume: Each session will deliver 240 to 720 mL of enteral formula. Feeding Duration: Each feeding session will last approximately 20 to 60 minutes.
Feeding Frequency: Enteral nutrition will be administered continuously for 20 hours per day via nasogastric tube. Feeding Volume: The total daily volume will be divided evenly over the 20-hour infusion period, based on individual nutritional requirements. Feeding Duration: Each 24-hour cycle includes 20 hours of continuous feeding followed by a 4-hour rest period.
Ankara Training and Research Hospital
Ankara, Turkey (Türkiye)
BMAL1 mRNA Expression Level
To evaluate the circadian rhythm in critically ill patients, BMAL1 gene expression will be measured using blood samples collected at 08:00, 16:00, and 00:00 on Day 1 and Day 7
Time frame: From randomization to the end of intervention (7 days)
CRY1 mRNA Expression Level
To evaluate the circadian rhythm in critically ill patients, CRY1 gene expression will be measured using blood samples collected at 08:00, 16:00, and 00:00 on Day 1 and Day 7
Time frame: From randomization to the end of intervention (7 days)
PER2 mRNA Expression Level
To evaluate the circadian rhythm in critically ill patients, PER2 gene expression will be measured using blood samples collected at 08:00, 16:00, and 00:00 on Day 1 and Day 7
Time frame: From randomization to the end of intervention (7 days)
Fasting Glucose Level
This parameter will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of Measure: mg/dL
Time frame: From randomization to Day 7
C-reactive protein (CRP)
This parameter will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of Measure: mg/L
Time frame: From randomization to Day 7
Lactate Level
This parameter will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of Measure: mmol/L
Time frame: From randomization to Day 7
Creatinine Level
This parameter will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of Measure: mg/dL
Time frame: From randomization to Day 7
Bicarbonate Level
This parameter will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of Measure: mmol/L
Time frame: From randomization to Day 7
White Blood Cell (WBC) Count
WBC count (x10³/μL) will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Lymphocyte Count
Lymphocyte Count (x10³/μL) will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Neutrophil Count
Neutrophil Count (x10³/μL) will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Hemoglobin Level
Hemoglobin Level will be analyzed from blood samples collected on the first and seventh days after randomization. Unit of measure: g/dL
Time frame: From randomization to Day 7
Platelet Count
Platelet Count (x10³/μL) will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Aspartate aminotransferase (AST) Levels
Aspartate aminotransferase (AST) (U/L) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Alanine aminotransferase (ALT) Levels
Alanine aminotransferase (ALT) (U/L) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Gamma glutamyl transferase (GGT) Levels
Gamma glutamyl transferase (GGT) (U/L) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Blood Urea Nitrogen (BUN) Levels
Blood Urea Nitrogen (BUN) (mg/dL) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Sodium Levels
Sodium (mmol/L) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Potassium Levels
Potassium (mmol/L) levels will be analyzed from blood samples collected on the first and seventh days after randomization.
Time frame: From randomization to Day 7
Acute Physiology and Chronic Health Evaluation II (APACHE-II) Score
The APACHE II score is a clinical tool used in intensive care units to assess the severity of a patient's illness and estimate the risk of hospital mortality. It is calculated based on physiological measurements, age, and chronic health conditions. Higher scores indicate more severe illness and a greater risk of death. Unit of Measure: Score (0-71 scale) Interpretation: Higher scores correspond to increased severity and mortality risk.
Time frame: First day of admission to the ICU
Sequential Organ Failure Assessment (SOFA) Score
The SOFA score evaluates the function of six organ systems-respiratory, cardiovascular, hepatic, coagulation, renal, and neurological-in critically ill patients. It is used to monitor the extent of organ dysfunction and predict clinical outcomes in the intensive care unit (ICU). Unit of Measure: Score (0-24 scale) Interpretation: Higher scores indicate greater organ dysfunction and worse prognosis.
Time frame: First day of admission to the ICU
Nutrition Risk in Critically ill (NUTRIC) Score
The NUTRIC score is a screening tool designed to identify critically ill patients at high nutritional risk. It incorporates factors such as age, severity of illness, comorbidities, and inflammation to guide nutritional interventions in the intensive care unit (ICU). Unit of Measure: Score (0-10 scale) Interpretation: Higher scores indicate greater nutritional risk.
Time frame: First day of admission to the ICU
Global Leadership Initiative on Malnutrition (GLIM) Criteria
The GLIM criteria provide a standardized framework to diagnose malnutrition based on a combination of phenotypic criteria (including weight loss, low BMI, and reduced muscle mass) and etiologic criteria (such as reduced food intake or disease burden/inflammation). These criteria are used across clinical settings to identify malnutrition and grade its severity. Unit of Measure: Categorical (e.g., malnutrition diagnosed: yes/no; severity graded as mild, moderate, or severe)
Time frame: First day of admission to the ICU
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