CIRCA-MED WP1 & WP3 - Circadian Rhythms in ICU Patients
September 3, 2026 updated by: Felix Balzer, Charite University, Berlin, Germany
Retrospective Characterization of Circadian Rhythms Using Vital Signs and Other Routine Data From Patients in the Intensive Care Unit
The goal of this retrospective exploratory study is to examine how the body's natural day-and-night rhythms and oscillatory patterns behave in people who were treated in the Intensive Care Unit (ICU).
The study uses routine clinical data that were already collected during and after the ICU stay, including post-discharge follow-up measurements (where available), such as heart rate, temperature, blood pressure, blood sugar, and insulin.
The researchers want to learn whether these measurements show daily patterns and whether patients can be grouped based on their oscillatory profiles.
The study also examines whether certain clinical factors such as illness severity scores, sedation levels, organ support treatments, or medications are associated with changes in these oscillatory rhythms.
The team will explore whether conditions that can develop during or after critical illness, such as delirium, muscle weakness, or Post-Intensive Care Syndrome (PICS), are linked to disturbed physiological rhythms.
Another goal is to test whether it is technically possible to show a patient's rhythm profile in real time using routine data from the ICU information system, evaluated retrospectively.
Digital tools called "Chrono-Apps" will be developed to display rhythmic information and may help clinicians adjust lighting to patient needs.
Study Overview
Status
Active, not recruiting
Conditions
Intervention / Treatment
Detailed Description
The investigators will retrospectively analyze periodic oscillations in clinical data, such as heart rate, temperature, blood glucose, insulin, or blood pressure, to identify parameters suitable for characterizing the physiological rhythms in hospitalized Intensive Care Unit (ICU) patients.
While these measurements typically show regular daily changes, also called oscillatory patterns, critical illness, continuous monitoring, and frequent medical interventions can disrupt them.
The study will investigate whether these patterns can be used to group patients into distinct temporal or rhythmic profiles.
The study will also examine whether certain clinical factors are linked to functioning or disrupted oscillatory patterns.
These factors include illness severity scores, sedation levels, organ support treatments, and medications.
Additionally, the researchers will explore whether temporal disruption is associated with key ICU complications, including delirium, ICU-acquired muscle weakness, and Post-Intensive Care Syndrome (PICS).
Finally, in a small cohort of ICU patients, the investigators will test personalized lighting regimens adapted to individual chronotypes.
This phase of the study aims to assess the robustness of routine clinical data for tailoring light exposure, validate a circadian entrainment algorithm, and evaluate potential sources of bias.
Real-time analyses of clinical data will be visualized as rhythm profiles via digital "Chrono-Apps" integrated into the electronic patient record.
These visualizations will support the day-to-day implementation of personalized lighting regimens that adapt dynamically to each patient's current rhythm status and clinical condition.
Study Type
Observational
Enrollment (Estimated)
25000
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
-
Berlin, Germany, 10117
- Institute of Medical Informatics, Charite University, Berlin
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
No
Sampling Method
Non-Probability Sample
Study Population
Charite University, Berlin, Germany
Description
Inclusion Criteria:
Primary Retrospective Cohort:
- Admitted to and treated in a participating Intensive Care Unit (ICU) between 2017 and 2024
- Minimum ICU length of stay of 3 days (≥ 72 hours)
- Age ≥ 18 years at the time of ICU admission
- All genders (male, female, diverse)
Cohorts from previous studies:
- Prior enrollment in one of the designated parent study protocols
- Availability of supplementary biological or metabolic data (e.g., clock gene expression, melatonin levels) suitable for exploratory association analyses
Exclusion Criteria:
- None
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
|---|---|
|
All retrospective patients between 2017 and 2024
Relates to retrospective data from all patients who spent at least three days in participating intensive care units at Charite University, Berlin, Germany between 2017 and 2024
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
|
|
Pa-COVID (DRKS00021688)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
|
|
SeptiCLOCK (NCT02044575)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
|
|
VITALITY (NCT02143661)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
|
|
TRG-N (ISRCTN77569430)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
These exposures represent metabolic consequences of critical illness: insulin sensitivity, muscle atrophy, and critical illness myopathy or ICU-acquired weakness.
|
|
CIPCIM2 (ISRCTN19392591)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
These exposures represent metabolic consequences of critical illness: insulin sensitivity, muscle atrophy, and critical illness myopathy or ICU-acquired weakness.
|
|
CGM (NCT02296372)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
|
|
HELIA-ICU (NCT05556811)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
These exposures reflect biological clock function: clock gene expression (if available in some cases), and melatonin levels.
|
|
PICS-Analyse (EA1/229/24)
|
These are the primary exposures and are used to detect oscillatory patterns and characterize circadian rhythms.
They include heart rate, body temperature, blood pressure, blood glucose, and insulin.
These are secondary exposures that may influence circadian rhythms: illness severity (e.g., Sequential Organ Failure Assessment (SOFA) score), sedation levels, organ support therapies (e.g., ventilation, dialysis, Extracorporeal Membrane Oxygenation (ECMO)), and medications administered during ICU stay (e.g., sedatives, vasopressors, corticosteroids).
These exposures represent complications that may be associated with circadian disruption: delirium, deep sedation, ICU-acquired muscle weakness, and post-intensive care syndrome.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Characterization of circadian periodicities and classification of time-varying patterns based on routine clinical data
Time Frame: From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Assessment of periodicities and time-varying patterns in routine clinical parameters, including heart rate, body temperature, blood pressure, blood glucose, and insulin levels.
Time-series analysis will be conducted to extract continuous metrics (amplitude, period, and phase).
Based on these metrics, patients will be classified into distinct categorical groups according to their periodic oscillation profiles.
|
From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Association between circadian rhythm category and clinical severity scores
Time Frame: From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Relationship between circadian rhythm classification and illness severity (e.g., SOFA score), sedation level, and use of organ support therapies.
|
From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
|
Association between circadian rhythm disruption and critical illness-related conditions
Time Frame: From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks), and post-ICU period (up to 3 and 6 months).
|
Presence of delirium, ICU-acquired muscle weakness/critical illness myopathy, and PICS in relation to circadian rhythm category.
Delirium will be measured with the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) binary scale (Positive/Negative).
|
From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks), and post-ICU period (up to 3 and 6 months).
|
|
Association between time-varying clinical patterns and external biological markers (from other studies)
Time Frame: Depending on individual study protocols, from ICU admission through 24 months post-discharge. Sampled daily to weekly during the ICU stay, followed by post-discharge examinations conducted at variable monthly intervals (a maximum of 5 visits).
|
Exploratory associations between oscillatory trends in routine clinical data and biological markers reported in other studies, such as clock gene expression, melatonin levels, insulin sensitivity, muscle atrophy, and critical illness myopathy.
Only associations will be evaluated.
|
Depending on individual study protocols, from ICU admission through 24 months post-discharge. Sampled daily to weekly during the ICU stay, followed by post-discharge examinations conducted at variable monthly intervals (a maximum of 5 visits).
|
|
Feasibility and Data Infrastructure for Real-Time Circadian Visualization (Chrono-Apps)
Time Frame: From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Evaluation of the technical feasibility and data integration requirements for generating real-time circadian visualizations within the Patient Data Management System (PDMS).
Feasibility will be assessed based on data completeness, sampling frequency compliance, latency of time-series data streaming from routine ICU monitors, and system stability required to display continuous circadian profiles via Chrono-Apps.
|
From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
|
Performance of Algorithm-Based Light Therapy Recommendations
Time Frame: From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Retrospective evaluation of the accuracy and stability of the time-series analysis designed to estimate circadian phase of routine clinical data (vital signs) and generate individualized lighting schedules.
|
From ICU admission to ICU discharge or death, whichever comes first (expected average duration of 4 weeks).
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2025
Primary Completion (Estimated)
May 31, 2029
Study Completion (Estimated)
September 30, 2029
Study Registration Dates
First Submitted
July 18, 2026
First Submitted That Met QC Criteria
September 3, 2026
First Posted (Actual)
September 10, 2026
Study Record Updates
Last Update Posted (Actual)
September 10, 2026
Last Update Submitted That Met QC Criteria
September 3, 2026
Last Verified
July 1, 2026
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- EA1/284/22
- 541063275 - TRR 418 (Other Grant/Funding Number: Deutsche Forschungsgemeinschaft (DFG, German Research Foundation))
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.