Light Therapy in Disorders of Consciousness: Behavioral, Neuroimaging and (Neuro)Physiological Assessments.

Study Overview
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Brief Summary
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In this randomized, double-blind, placebo controlled project, the investigators would like to assess the effect of a specific light, as compared to placebo light, on wakefulness (circadian rhythms, homeostasy, sleep-wake cycle), awareness (perceptual and self consciousness), cognition (attention, memory) and underlying brain activity (electrophysiology and neuroimaging)

Detailed Description
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The investigators will use behavioral (CRS-R, CAP, actimeter, brainstem reflexes), physiological (body core temperature, saliva, urine, heart rate, blood sample), neuroimaging and neurophysiological tools (PET, fMRI, TMS-EEG, resting-state and auditory paradigm EEG) before, during and after treatment.

Official Title
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Luminothérapie Chez Les Patients présentant un état de la Conscience altérée: évaluations Comportementale, de Neuroimagerie et (Neuro)Physiologique.

Conditions
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Disorder of Consciousness

Intervention / Treatment
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* Device: Light therapy - active
* Device: Placebo light


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: disorder of consciousness 6 weeks post-injury Exclusion Criteria: dysautonomia acute illnesses (infections with fever) medication that is known to affect circadian rhythmicity (melatonin) uncorrected sensorial deficits or documented history of significant neurological, neurosurgical, developpemental or psychiatric disorders previously known cerebral lesions prior to the brain's insult that lead to disorder of consciousness any contraindication to MRI, EEG, TMS-EEG, or PET (e.g., electronic implanted devices, active epilepsy, external ventricular drain) not medically stable

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 80 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: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real light exposition by the mean of Luminette®<br>All patients will be exposed to a real light (1500 lux, 470 nm) during the treatment phase, 3 times per day (morning, afternoon and evening) for 60 minutes each via goggles providing light at the eyes level. Meanwhile, different assessments will be performed in order evaluating the potential effects of provided light in comparison to placebo ligh. Patients will be given behavioral assessments (Coma Recovery Scale-Revised, Nociception Coma Scale-Revised, brainstem reflexes,...), physiological (body core temperature, saliva, urine, heart rate, blood sample), neuroimaging and neurophysiological tools (PET, fMRI, TMS-EEG, resting-state and auditory paradigm EEG) before, during and after treatment. | Device: Light therapy - active<br>* Active light will be used for one week, as compared to placebo light.<br>* Other names: Real light stimulation;|
| Placebo Comparator: Placebo light exposition by the mean of Luminette®<br>All patients will also be exposed to a placebo light (80 lux, 470 nm) during the treatment phase, 3 times per day (morning, afternoon and evening) for 60 minutes each via goggles providing light at the eyes level. Meanwhile, different assessments will be performed in order evaluating the potential effects of provided light in comparison to placebo light. Patients will be given behavioral assessments (Coma Recovery Scale-Revised, Nociception Coma Scale-Revised, brainstem reflexes,...), physiological (body core temperature, saliva, urine, heart rate, blood sample), neuroimaging and neurophysiological tools (PET, fMRI, TMS-EEG, resting-state and auditory paradigm EEG) before, during and after treatment. | Device: Placebo light<br>* Placebo light will be used for one week, as compared to real light exposition.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Coma Recovery Scale-Revised scores. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with behavioral analyses and diagnosis through the CRS-R results. | 4 weeks study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in sleep-wake cycles through the Nociception Coma Scale-Revised, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with behavioral analyses through the NCS-R results. | 4 weeks study | 
| Change in sleep-wake cycles through the actimetry, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with behavioral analyses through the arms movements measured with the actimetry. | 4 weeks study | 
| Change in sleep-wake cycles through the brain metabolism with Positron Emission Tomography, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with PET scan analyses. | 4 weeks study | 
| Change in sleep-wake cycles through the hemodynamic function of the brain with functional Magnetic Resonance Imaging, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with fMRI analyses. | 4 weeks study | 
| Change in sleep-wake cycles through the electrical activity of the brain with electroencephalography, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with EEG analyses. | 4 weeks study | 
| Change in sleep-wake cycles through analyses of melatonine hormone, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with urine analyses. | 4 weeks study | 
| Change in sleep-wake cycles through temperature measurements, after the exposition of real light instead of placebo light. | Identify the improvement in sleep-wake cycle and circadian rhythm after the real light therapy exposure, with body core temperature analyses. | 4 weeks study | 
| Change in the outcomes by the assessment of the Glasgow Outcome Scale Extended, after the study. | Improvement of the recovery's outcomes after the end of the real light therapy exposure. | 2 years after |