Proof of Concept Trial to Confirm That the Recovery of Patients Treated in the Intensive Care Unit Requiring Mechanical Ventilation is Beneficially Affected by the Environmental Simulation of Daytime and Night Time Alternation as Well as by the Nutrition Protocol Corresponding to the Daily Rhythm

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the environmental simulation of daytime and night time alternation as well as by the nutrition protocol corresponding to the daily rhythm are beneficially affect the recovery of patients treated in the Intensive Care Unit (ICU) requiring mechanical ventilation.

Detailed Description
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The homeostasis of human body is significantly disturbed when organs' work-relax periods are not harmonized. Intensive Care Unit (ICU) patient's circadian rhythm is almost inevitably upset as a result of their disease and/or medical intervention. There are numerous animal studies prove that circadian rhythm and periodic dynamics are directly related to healing time and hence, mortality rate. Although, one of the main messengers of circadian synchronization is melatonin, it is overridden by temperature, and a number of other factors from e.g. the digestive tract. If the circadian rhythm is disturbed, the function of different organ systems becomes desynchronized and chaotic. ICU environment and patient-care activities brings major drawbacks as well mainly by necessary presence of noise and light. It has been shown that ICU settings have an impact on patients' sleep, which can easily lead to delirium and circadian disruption. There are significant data showing strong correlation between delirium and ICU length of stay/ mortality. The focus of this study is the environmental modulation at the ICU with controlled light, noise and nutrition conditions. Controlled light conditions are created with artificial light during daytime and sleeping mask during night time. Earplugs are used during night time for controlled noise conditions. Nutrition is carried out only during daytime both in case of enteral and parenteral feeding.

Official Title
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Proof of Concept Trial to Confirm That the Recovery of Patients Treated in the Intensive Care Unit Requiring Mechanical Ventilation is Beneficially Affected by the Environmental Simulation of Daytime and Night Time Alternation as Well as by the Nutrition Protocol Corresponding to the Daily Rhythm

Conditions
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Critical Illness, Mechanical Ventilation

Intervention / Treatment
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* Other: Controlled light and noise
* Other: Controlled nutrition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years or older Requiring treatment at the intensive care unit including mechanical ventilation Admission at the intensive care unit was done within 24 hours before randomization Written and signed patient information sheet and informed consent form obtained by the study participant or by his/her legal representative Exclusion Criteria: Traumatic brain injury Multiple trauma Severe damage of the eye/optic nerve Blindness Post CPR Unlikely to survive 24 hours Involvement of the central nervous system (trauma, bleeding, infection, ischemia, etc.) Intracranial space occupying process Increased intracranial pressure Narcolepsy Huntington's disease Hypothermia Pregnancy

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Controlled light, noise and nutrition<br>Simultaneously with the standard treatment performed at the clinical trial site environmental simulation of night time and daytime alternation as well as the nutrition protocol corresponding to the daily rhythm will be applied. | Other: Controlled light and noise<br>* Purpose: The day-night ratio of the environmental illumination (limit 8 lux) and that of the noise level (limit 20 dBA) must correspond to the necessary value required by a healthy human body as defined by the National Sleep Foundation (USA). Implementation: Simulation of the daytime period is performed with blue predominant artificial light with colour temperature between 5500 and 8000 K with lux values of 1000-1200 measured at the head of the patient. Simulation of the nighttime period is performed with a sleeping mask and earplugs.<br>* Other names: Environmental simulation of the daytime and night time alternation;Other: Controlled nutrition<br>* In compliance with the standard daily nutrition protocol, nutrition is carried out only during daytime both in case of enteral and parenteral feeding in accordance with European Society for Clinical Nutrition and Metabolism 2016 guidelines. Nutritional regimen should be stopped for 8 hours/24 at night (non-nutritional period may be depending on the work schedule of the actual ICU) , even if the daily energy/protein target is not reached.<br>* Other names: Nutrition protocol that is in accordance with the daily rhythm;|
| Experimental: Controlled light and noise<br>Simultaneously with the standard treatment performed at the clinical trial site environmental simulation of night time and daytime alternation as well as the continuous nutrition (in accordance with the clinical trial site's standard practice) will be applied. | Other: Controlled light and noise<br>* Purpose: The day-night ratio of the environmental illumination (limit 8 lux) and that of the noise level (limit 20 dBA) must correspond to the necessary value required by a healthy human body as defined by the National Sleep Foundation (USA). Implementation: Simulation of the daytime period is performed with blue predominant artificial light with colour temperature between 5500 and 8000 K with lux values of 1000-1200 measured at the head of the patient. Simulation of the nighttime period is performed with a sleeping mask and earplugs.<br>* Other names: Environmental simulation of the daytime and night time alternation;|
| No Intervention: Control<br>The treatment of the study subject will be performed based on the clinical trial site's standard practice without environmental simulation or changes in the nutrition protocol. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the Multiple Organ Dysfunction Score value (delta MODS) from baseline to the end of the study treatment | The primary efficacy endpoint is the change in MODS scale from baseline to the end of the study treatment period, i.e. deltaMODS. Since the length of ICU stay may be different for subjects, the MODS rate of change per day (deltaMODS/day) will be the primary measure to characterize the treatment effect. | Over the ICU treatment period but no more than 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of the MODS value (delta MODS) between worst and last score during the study treatment | Change of the MODS value between worst and last score over the ICU treatment period but no longer than 10 days. | Over the ICU treatment period but no more than 10 days | 
| Number of participants with gastric retention | Number of participants with at least 250ml gastric retention at least one time | over the ICU treatment period but no more than 10 days | 
| Number of participants with delirium | Number of participants with at least one evaluated Intensive Care Delirium Screening Checklist (ICDSC) score between 4-8 | over the ICU treatment period but no more than 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Circadian rhythm, Critical Illness, Mechanical ventilation, Environmental modulation