Circadian Rhythm in Critical Illness

NCT07063303 | Completed

• 1 other identifier: atılımnut
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Does intermittent feeding improve circadian rhythms in ICU patients?
2. 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.
3. 3.Receive intermittent enteral feeding or continuous enteral feeding for at least 10 days
4. 4.Undergo blood sample collection at three time points daily (morning, afternoon, midnight) to analyze circadian gene expression and metabolic markers
5. 5.Have their clinical condition, nutrition status, and recovery progress monitored throughout the study

Conditions

Critical Illness

Keywords

critical illness; intermittent feeding; circadian rhythm

Outcome Measures

Primary Outcomes (3)

• 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

  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

  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

  From randomization to the end of intervention (7 days)

Secondary Outcomes (20)

• Fasting Glucose Level

  From randomization to Day 7

• C-reactive protein (CRP)

  From randomization to Day 7

• Lactate Level

  From randomization to Day 7

• Creatinine Level

  From randomization to Day 7

• Bicarbonate Level

  From randomization to Day 7

Study Arms (2)

Intermittent Feeding Group

ACTIVE COMPARATOR

Patients receive enteral nutrition at scheduled intervals to align with circadian rhythms.

Other: Intermittent feeding

Continuous Feeding Group

ACTIVE COMPARATOR

Patients receive enteral nutrition continuously, following the standard ICU practice.

Other: Continuous feeding

Interventions

Intermittent feeding OTHER

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.

Intermittent Feeding Group

Continuous feeding OTHER

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.

Continuous Feeding Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ICU admission for enteral feeding via a gastric tube
• Expected ≥10 days of enteral nutrition
• Age ≥18 years

You may not qualify if:

• Age \<18 years
• Pregnancy
• Gastrointestinal surgery or diseases
• Tolerance issues with enteral feeding
• Parenteral feeding requirement

Sponsors & Collaborators

• Atılım University: lead

Study Sites (1)

Ankara Training and Research Hospital

Ankara, Turkey (Türkiye)

Location

Related Publications (16)

• Sagun E, Akyol A, Kaymak C. Chrononutrition in Critical Illness. Nutr Rev. 2025 Mar 1;83(3):e1146-e1157. doi: 10.1093/nutrit/nuae078.

  PMID: 38904422 BACKGROUND

• Theilla M, Rattanachaiwong S, Kagan I, Rigler M, Bendavid I, Singer P. Validation of GLIM malnutrition criteria for diagnosis of malnutrition in ICU patients: An observational study. Clin Nutr. 2021 May;40(5):3578-3584. doi: 10.1016/j.clnu.2020.12.021. Epub 2020 Dec 29.

  PMID: 33413910 BACKGROUND

• Jensen GL, Cederholm T, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, de Baptista GA, Barazzoni R, Blaauw R, Coats AJS, Crivelli A, Evans DC, Gramlich L, Fuchs-Tarlovsky V, Keller H, Llido L, Malone A, Mogensen KM, Morley JE, Muscaritoli M, Nyulasi I, Pirlich M, Pisprasert V, de van der Schueren M, Siltharm S, Singer P, Tappenden KA, Velasco N, Waitzberg DL, Yamwong P, Yu J, Compher C, Van Gossum A. GLIM Criteria for the Diagnosis of Malnutrition: A Consensus Report From the Global Clinical Nutrition Community. JPEN J Parenter Enteral Nutr. 2019 Jan;43(1):32-40. doi: 10.1002/jpen.1440. Epub 2018 Sep 2.

  PMID: 30175461 BACKGROUND

• Van Dyck L, Vanhorebeek I, Wilmer A, Schrijvers A, Derese I, Mebis L, Wouters PJ, Van den Berghe G, Gunst J, Casaer MP. Towards a fasting-mimicking diet for critically ill patients: the pilot randomized crossover ICU-FM-1 study. Crit Care. 2020 May 24;24(1):249. doi: 10.1186/s13054-020-02987-3.

  PMID: 32448392 BACKGROUND

• 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.

  PMID: 35797531 BACKGROUND

• Sunderram J, Sofou S, Kamisoglu K, Karantza V, Androulakis IP. Time-restricted feeding and the realignment of biological rhythms: translational opportunities and challenges. J Transl Med. 2014 Mar 28;12:79. doi: 10.1186/1479-5876-12-79.

  PMID: 24674294 BACKGROUND

• Ren CJ, Yao B, Tuo M, Lin H, Wan XY, Pang XF. Comparison of sequential feeding and continuous feeding on the blood glucose of critically ill patients: a non-inferiority randomized controlled trial. Chin Med J (Engl). 2021 Jul 20;134(14):1695-1700. doi: 10.1097/CM9.0000000000001684.

  PMID: 34397596 BACKGROUND

• Dong J, Liu R, Li L, Yao L. [Effects of intermittent feeding and continuous feeding on muscle atrophy and nutritional status in critically ill patients]. Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2021 Jul;33(7):844-848. doi: 10.3760/cma.j.cn121430-20210408-00517. Chinese.

  PMID: 34412755 BACKGROUND

• Ichimaru S. Methods of Enteral Nutrition Administration in Critically Ill Patients: Continuous, Cyclic, Intermittent, and Bolus Feeding. Nutr Clin Pract. 2018 Dec;33(6):790-795. doi: 10.1002/ncp.10105. Epub 2018 Jun 20.

  PMID: 29924423 BACKGROUND

• Jobanputra AM, Scharf MT, Androulakis IP, Sunderram J. Circadian Disruption in Critical Illness. Front Neurol. 2020 Aug 11;11:820. doi: 10.3389/fneur.2020.00820. eCollection 2020.

  PMID: 32849248 BACKGROUND

• Acuna-Fernandez C, Marin JS, Diaz-Casado ME, Rusanova I, Darias-Delbey B, Perez-Guillama L, Florido-Ruiz J, Acuna-Castroviejo D. Daily Changes in the Expression of Clock Genes in Sepsis and Their Relation with Sepsis Outcome and Urinary Excretion of 6-Sulfatoximelatonin. Shock. 2020 May;53(5):550-559. doi: 10.1097/SHK.0000000000001433.

  PMID: 31403491 BACKGROUND

• Diaz E, Diaz I, Del Busto C, Escudero D, Perez S. Clock Genes Disruption in the Intensive Care Unit. J Intensive Care Med. 2020 Dec;35(12):1497-1504. doi: 10.1177/0885066619876572. Epub 2019 Sep 11.

  PMID: 31510864 BACKGROUND

• Maas MB, Iwanaszko M, Lizza BD, Reid KJ, Braun RI, Zee PC. Circadian Gene Expression Rhythms During Critical Illness. Crit Care Med. 2020 Dec;48(12):e1294-e1299. doi: 10.1097/CCM.0000000000004697.

  PMID: 33031153 BACKGROUND

• Beyer SE, Salgado C, Garcao I, Celi LA, Vieira S. Circadian rhythm in critically ill patients: Insights from the eICU Database. Cardiovasc Digit Health J. 2021 Feb 17;2(2):118-125. doi: 10.1016/j.cvdhj.2021.01.004. eCollection 2021 Apr.

  PMID: 35265899 BACKGROUND

• Coiffard B, Diallo AB, Culver A, Mezouar S, Hammad E, Vigne C, Nicolino-Brunet C, Dignat-George F, Baumstarck K, Boucekine M, Leone M, Mege JL. Circadian Rhythm Disruption and Sepsis in Severe Trauma Patients. Shock. 2019 Jul;52(1):29-36. doi: 10.1097/SHK.0000000000001241.

  PMID: 30074979 BACKGROUND

• Neves AR, Albuquerque T, Quintela T, Costa D. Circadian rhythm and disease: Relationship, new insights, and future perspectives. J Cell Physiol. 2022 Aug;237(8):3239-3256. doi: 10.1002/jcp.30815. Epub 2022 Jun 13.

  PMID: 35696609 BACKGROUND

MeSH Terms

Conditions

Critical Illness

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Aslı Akyol Mutlu, Prof.

  Hacettepe University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Patients admitted to the ICU who require enteral feeding for at least 10 days are randomly assigned to one of two groups: Intermittent Feeding Group, where enteral product is administered in scheduled intervals aligned with circadian rhythms. Continuous Feeding Group, following the standard ICU practice of continuous enteral nutrition.

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: July 14, 2025
• Study Start: July 1, 2025
• Primary Completion: September 29, 2025
• Study Completion: September 29, 2025
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)