Stabilization of Circadian Rhythms in Delirious ICU Patients Through Light Intervention

Charite University, Berlin, Germany40 enrolled

Overview

The investigators will examine the effects of dynamic light therapy on circadian rhythms in delirious 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Circadian Dysrhythmia

Interventions

Dynamic Light Therapy Device, LSA-1DEVICE

Dynamic Light Therapy

Dynamic Light Therapy Device, LSA-2DEVICE

Light Exposition

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 ≥ 2 days * Positive delirium during and up to a maximum of 30 days after study inclusion (determined by CAM-ICU, at least once per shift) 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 * Amaurosis * 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 * 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 * Optic neuritis within the last 3 months * Travel across two time zones within 3 months prior to study screening * Women who are pregnant, have a positive pregnancy test, are breastfeeding or plan to become pregnant during the course of this clinical trial * Therapy-refractory blood coagulation disorder and inability to consent are exclusion criteria for a muscle biopsy

Locations (2)

Department of Anesthesiology and Intensive Care Medicine (CCM/CVK), Campus Charité Mitte

Berlin, Germany

RECRUITING

Department of Anesthesiology and Intensive Care Medicine (CCM/CVK), Campus Virchow Klinikum

Berlin, Germany

RECRUITING

Outcomes

Primary Outcomes

Rhythmicity of melatonin concentration

Prevalence of physiological circadian rhythmicity measured by serum melatonin concentrations.

Time frame: Plasma melatonin levels will be assessed for every 4 hours on day 1 and day 5 after study inclusion

Secondary Outcomes

Clock genes

Prevalence of physiological circadian rhythmicity measured by expression activity of clock genes.

Time frame: Clock gene expression levels will be assessed for every 4 hours on day 1 and day 5 after study inclusion.

Metabolomics

Prevalence of physiological circadian rhythmicity measured by metabolomic concentrations.

Time frame: Metabolomic measurements be assessed up to 3 (6-9) months.

Proteomics

Prevalence of physiological circadian rhythmicity measured by proteomic concentrations.

Time frame: Proteomic measurements will be assessed up to 3 (6-9) months.

Inflammation parameters

Prevalence of physiological circadian rhythmicity measured by inflammation parameters (cytokines, chemokines, extracellular mitochondria concentrations.

Time frame: Inflammation parameter levels will be assessed up to 3 (6-9) months.

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)

Time frame: 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

Central Contacts

Claudia Spies, MD, Prof.

CONTACT

+49 30 450 55 11 02 claudia.spies@charite.de

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

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))

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: Participants will be followed up until hospital dischargean expected average of 7 days.

Sepsis

Does patient fulfil sepsis criteria (Yes/No)

Time frame: 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)

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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).

Time frame: 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).

Time frame: Up to 3 (6-9) months

Analysis of the sleep architecture measured by polysomnography 1

Binary scale (Positive/Negative). All participants will be undergoing a polysomnography in the St. Hedwig hospital.

Time frame: Up to 3 (6-9) months

Analysis of the sleep architecture measured by polysomnography 2

All participants will be undergoing a polysomnography one night in the Intensive Care Unit.

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

MCTQ (Munich Chronotype Questionnaire)

In this questionnaire, the typical sleep behaviour over the past 4 week will be reported

Time frame: Up to 3 (6-9) months

Actigraphy

Aktigraphy is measured by ActLumus in a time period of six weeks.

Time frame: Up to 3 (6-9) months

Sleep diary

Sleep parameter are documented by a sleep diary in a time period of six weeks.

Time frame: Up to 3 (6-9) months

Molecular data

Molecular data from muscle needle biopsies in the morning and evening on a study day

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Physiotherapy

Physiotherapy is measured by a questionnaire.

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Nutritional Therapy

Nutritional Therapy is measured by chart review.

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Nutritional Therapy Complications

Nutritional Therapy Complications are measured by chart review.

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Target protein intake

Rate in patient days on which the target protein intake was achieved

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Adherence to the diet plan

Rate of days with adherence to the diet plan (yes/no)

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Composition of the administered food

Composition of the administered food is measured by macro- and micronutrients according to documentation

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Daily feeding breaks

Daily feeding breaks are measured in hours

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Wheather data

Weather data are extracted from German Wheather Administration and Federal Environment Agency.

Time frame: Participants will be followed up until discharge from the intensive care unit (maximum up to day 5)

Cognition 1

Cognition 1 is measured by MiniCog

Time frame: Up to 3 (6-9) months

Cognition 2

Cognition 2 is measured by Animal Naming Test

Time frame: Up to 6 months

Cognition 3

Cognition 3 is measured by Trail Making Tests A\&B

Time frame: Up to 3 (6-9) months

Mental impairments

Mental impairments are measured using the PHQ-4. The PHQ-4 (Patient Health Questionnaire-4) is a brief, 4-item self-report tool screening for anxiety and depression symptoms, combining the PHQ-2 (depression) and GAD-2 (anxiety) scales, with scores from 0-12 indicating increasing symptom severity (Normal: 0-2, Mild: 3-5, Moderate: 6-8, Severe: 9-12). Each item asks how often in the last two weeks you've been bothered by something, with responses 0 (not at all) to 3 (nearly every day), and scores ≥3 on the first two items suggest depression, while ≥3 on the last two suggest anxiety, warranting further clinical assessment.

Time frame: Up to 3 (6-9) months

Quality of life 1

Quality of life 1 is measured by EQ-5D-5L. The EQ-5D-5L is a widely used patient-reported outcome (PRO) tool measuring health-related quality of life with five dimensions (Mobility, Self-care, Usual Activities, Pain/Discomfort, Anxiety/Depression), each having five severity levels (no to extreme problems) An EQ-5D-5L result describes health status in 5 dimensions on a 5-point scale (none to extreme problems) and is summarized into a single index value (usually 0 to 1), with 1 representing perfect health, supplemented by a visual analog scale (EQ VAS) value for self-assessment of health.

Time frame: Up to 3 (6-9) months

Quality of life 2

Quality of life 2 is measured by WHODAS 2.0. The WHODAS (World Health Organization Disability Assessment Schedule) 2.0 12-item version is a standardized, cross-cultural tool measuring health and disability by assessing difficulties in six core domains (cognition, mobility, self-care, getting along, life activities, participation) over the past 30 days, and contains 2 questions per domain. WHODAS 2.0 uses a 1-5 Likert scale (none to extreme difficulty) for its items, with scores summed and converted to a 0-100 standardized score (higher is worse), offering simple addition for general scoring or complex Item Response Theory (IRT) for weighted domain scores, with a threshold of \>10 (12-item) indicating top 10% disability, all to assess disability across six domains.

Time frame: Up to 3 (6-9) months

Mortality

Mortality is measured by statistical data.

Time frame: Up to 6 months