Circadian Rhythm in Critical Illness

NCT ID: NCT07063303

Last Updated: 2025-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-01

Study Completion Date

2025-09-29

Brief Summary

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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

Detailed Description

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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.

Conditions

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Critical Illness

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

SUPPORTIVE_CARE

Blinding Strategy

SINGLE

Participants

Study Groups

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Intermittent Feeding Group

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

Group Type ACTIVE_COMPARATOR

Intermittent feeding

Intervention Type 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.

Continuous Feeding Group

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

Group Type ACTIVE_COMPARATOR

Continuous feeding

Intervention Type 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.

Interventions

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Intermittent feeding

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.

Intervention Type OTHER

Continuous feeding

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Atılım University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Aslı Akyol Mutlu, Prof.

Role: STUDY_CHAIR

Hacettepe University

Locations

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Ankara Training and Research Hospital

Ankara, , Turkey (Türkiye)

Site Status

Countries

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Turkey (Türkiye)

References

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

Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
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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.

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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.

Reference Type BACKGROUND
PMID: 35797531 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24674294 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34397596 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 34412755 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29924423 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 32849248 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31403491 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 31510864 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 33031153 (View on PubMed)

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.

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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.

Reference Type BACKGROUND
PMID: 30074979 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 35696609 (View on PubMed)

Other Identifiers

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atılımnut

Identifier Type: -

Identifier Source: org_study_id

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