Enhancement of Circadian Rhythms in ICU Patients Through Light Intervention

Study Overview
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Brief Summary
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The investigators will examine the effects of dynamic light therapy on circadian rhythms in intensive care unit (ICU) patients. In a randomized controlled trial (RCT), they will investigate the effects of a specific light algorithm on rhythms of serum melatonin, clock gene expression, the proteome, and metabolome, compared to standard hospital lighting, supported by the data science algorithms to improve vital-based algorithms with light interventions.

Official Title
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Enhancement of Circadian Rhythms in ICU Patients Through Light Intervention

Conditions
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Circadian Dysrhythmia

Intervention / Treatment
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* Device: Dynamic Light Therapy Device, LSA-1
* Device: Dynamic Light Therapy Device, LSA-2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient capable of giving consent or additionally existing legal caregiver or authorized/spouse representative in case of non-consenting patients in the intensive care unit Male and female patients with age ≥ 18 years Expected intensive care unit stay ≥ 5 days Exclusion Criteria: Participation in other clinical studies during the study period and ten days before Previous ICU treatment during the current hospital stay Patients with psychiatric diseases Patients with a history of stroke and known severe residual cognitive deficits Patients with a history of cardiopulmonary arrest or pulseless electric activity with cardiopulmonary resuscitation followed by therapeutic hypothermia during entire hospital stay Analphabetism Anacusis or Hypoacusis with hearing aid device, Amaurosis Accommodation in an institution due to an official or judicial order History of sleep-related breathing disorders History or suspicion of hypoxic brain damage History or suspicion of elevated intracranial pressure in the last 7 days before study inclusion Patients with an open chest after cardiac surgery Patient has a power of attorney or patient's provision, where he/she refuses participation in any clinical trial The informed consent of the patient or the subject's legally acceptable representative can't be obtained in time History of photoallergic reactions or history of visually triggered seizures Severe eye diseases (e.g. retinopathy, glaucoma) or high sensitivity to bright light Patients with liver cirrhosis Patients with a probability of survival <24h

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Evaluation of Specific Light Algorithms (Dynamic Light Therapy Devices, LSA-1 and LSA-2) to Maintain and Restore Circadian Melatonin Rhythmicity in Critically Ill Patients
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LSA-1<br>Light Scheduling Algorithm-1 (LSA-1): High circadian effective irradiances | Device: Dynamic Light Therapy Device, LSA-1<br>* Dynamic Light Therapy<br>|
| Active Comparator: LSA-2<br>Light Scheduling Algorithm-2 (LSA-2): Irradiance levels comparable to conventional hospital lighting (control group). | Device: Dynamic Light Therapy Device, LSA-2<br>* Dynamic Light Therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rhythmicity of melatonin concentration | Prevalence of physiological circadian rhythmicity measured by serum melatonin concentrations. | Plasma melatonin levels will be assessed for a maximum of five 24-hour periods. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clock genes | Prevalence of physiological circadian rhythmicity measured by expression activity of clock genes. | Clock gene expression levels will be assessed for a maximum of five 24-hour periods. | 
| Metabolomics | Prevalence of physiological circadian rhythmicity measured by metabolomic concentrations. | Metabolomic measurements be assessed for a maximum of five 24-hour periods. | 
| Proteomics | Prevalence of physiological circadian rhythmicity measured by proteomic concentrations. | Proteomic measurements will be assessed for a maximum of five 24-hour periods. | 
| Inflammation parameters | Prevalence of physiological circadian rhythmicity measured by inflammation parameters (cytokines, chemokines, extracellular mitochondria concentrations. | Inflammation parameter levels will be assessed for a maximum of five 24-hour periods. | 
| Incidence of intensive care unit delirium | Delirium will be measured with the Confusion Assessment Method for the intensive care unit (CAM-ICU), Binary scale (Positive/Negative) | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Delirium-free days in the intensive care unit | Delirium-free days will be measured in day without positive delirium scoring (Confusion Assessment Method for the intensive care unit (CAM-ICU), Binary scale (Negative)) | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Delirium Severity | Delirium severity will be measured with the Intensive Care Delirium Screening Checklist (ICDSC). The higher the score the worse - higher score = higher delirium severity(ICDSC) | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Depth of Sedation | Level of sedation will be measured with the Richmond Agitation-Sedation-Scale (RASS), -5 to +4, negative scores translates to a higher degree of sedation. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Level of analgesia 1 | Severity of pain will be measured with the Numeric Rating Scale (NRS). A higher score corresponds to a higher severity of pain.Score values from 0 to 10. A higher score means worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Level of analgesia 2 | Severity of pain will be measured with the Visualized Numeric Rating Scale (NRS-V). A higher score corresponds to a higher severity of pain.Score values from 0 to 10. A higher score means worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Level of analgesia 3 | Severity of pain will be measured with the Faces Pain Scale-Revised (FPS-R). A higher score corresponds to a higher severity of pain.Score values from 0 to 10. A higher score means worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Level of analgesia 4 | Severity of pain will be measured with the Behavioral Pain Scale (BPS) . A higher score corresponds to a higher severity of pain.Score values from 3 to 12. A higher score means worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Level of analgesia 5 | Severity of pain will be measured with the Behavioral Pain Scale for Non- Intubated (BPS-NI). A higher score corresponds to a higher severity of pain. A higher score corresponds to a higher severity of pain.Score values from 3 to 12. A higher score means worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Total amount of opioids | Total amount of opioids administered per ICU treatment day will be measured in with morphine equivalents for each administered opioids. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Total amount of sedatives | Total amount of sedatives administered per ICU treatment day by dose summation for each sedative. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Duration of ventilation | Duration of invasive and non-invasive ventilation in hours | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| ICU length of stay | ICU length of stay will be measured in days | Participants will be followed up until ICU discharge, an expected average of 3 days. | 
| Hospital length of stay | Hospital length of stay will be measured in days | Participants will be followed up until hospital dischargean expected average of 7 days. | 
| Sepsis | Does patient fulfil sepsis criteria (Yes/No) | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Septic shock | Does patient fulfil criteria for septic shock (Yes/No) | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Sequential Organ Failure Assessment (SOFA-Score) | Predicts ICU mortality based on lab results and clinical data. . Score values between 0 and max. 24. Higher scores mean worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Simplified Acute Physiology Score (SAPS II) | Estimates mortality in ICU patients, comparable to APACHE II.Score values between 0 and max. 163. Higher scores mean worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Therapeutic Intervention Scoring System (TISS-28) | The Simplified Therapeutic Intervention Scoring System TISS-28 consists of 28 items. It is intended to accurately measure the level of care required for a patient in the Intensive Care Unit (ICU). Score values between 0 and max. 78. Higher scores mean higher level of required care for ICU patients. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Acute Physiological and Chronic Health Evaluation 2 Score (APACHE II) | The Acute Physiology and Chronic Health Evaluation (APACHE II) is a severity score and mortality estimation tool developed from a large sample of ICU patients in the United States.. Score values between 0 and max. 71. Higher scores mean worse outcome. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Medical Research Council (MRC) Score | The muscle scale grades muscle power on a scale of 0 to 5 (5= Muscle contracts normally against full resistance.; 0 = No movement is observed). | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Hand strength measurements | Hand grip strength is measured with a dynometer. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Intensive Care Mobility Scale | To record the patient's highest level of mobility in the Intensive Care Unit. Scale from 0 to 10. 0 meaning no movement and 10 mean walking independently. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| FIM Score (Functional Independence Measure) | FIM™ is comprised of 18 items, grouped into 2 subscales - motor and cognition. Each item is scored on a 7 point ordinal scale, ranging from a score of 1 to a score of 7. The higher the score, the more independent the patient is in performing the task associated with that item | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Mean blood glucose (mg/dl) | Plasma glucose (PG) levels are determined by taking a blood sample from participants. It can be measured in mg/dL. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Blood glucose variability (SD in mg/dl) | Blood glucose variability (SD in mg/dl) represents how much glucose levels fluctuate over time from a given average. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Percentage of time in target glucose range (%) | Blood glucose levels outside the ranges listed in the blood sugar levels chart by age above are categorized as either high or low blood sugar. | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Insulin requirement (IU/kg/h) | The amount of insuline is measured in units (IU). | Participants will be followed up until discharge from the intensive care unit (maximum up to day 5) | 
| Post Intensive Care Syndrome (PICS) | Binary scale (Positive/Negative). Diagnosis of PICS is defined by a new impairment or worsening of the health condition after intensive care unit stay and a clinically significant distress in at least one of the following outcome measurement instruments: Patient Health Questionnaires (PHQ-9, PHQ-8, PHQ-4), Generalized Anxiety Disorder Scales (GAD-2 and GAD-7), Impact of Event Scale Revised (IES-R), MiniCog, Animal Naming Test, Trail Making Test (TMT-A, TMT-B), Repeatable Battery for the Assessment of Neuropsychological Satus (RBANS), Timed Up-and-Go (TUG), Handgrip Strength, EQ-5D-5L, subjective assessment NRS, WHO Disability Assessment Schedule (WHODAS), Short Physical Performance Battery (SPPB). | Up to 6 months | 
| Analysis of the sleep architecture measured by polysomnography | Binary scale (Positive/Negative). All participants will be undergoing a polysomnography as part of their clinical care in the Post Intensive Care Syndrome ambulance. | Up to 6 months |