Prefontal tDCS in Patients With Disorders of Consciousness: Neurophysiological and Behavioural Outcomes

Study Overview
=================
Brief Summary
-----------------
Non-invasive brain stimulations techniques have recently shown promising results in patients with disorders. Notably, transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex has proved to be effective in improving signs of consciousness in about 50% of patients in MCS either after a single stimulation or after repeated sessions. However, brain mechanisms underlying tDCS effects remain poorly understood. Here we aim to assess the effects of prefrontal tDCS on neurophysiological (i.e., electroencephalography - EEG - primary outcome) and behavioral (secondary outcome) measures in severely brain-injured patients with DOC.

Detailed Description
-----------------
Currently, therapeutic options for severely brain-injured patients with disorders of consciousness (DOC), including patients in unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), are limited and still need to be improved to influence long-term outcomes. Non-invasive brain stimulations (NIBS) techniques have recently shown promising results in DOC. Notably, transcranial direct current stimulation (tDCS) applied over the left dorsolateral prefrontal cortex has proved to be effective in improving signs of consciousness in about 50% of patients in MCS either after a single stimulation or after repeated sessions. However, brain mechanisms underlying tDCS effects remain poorly understood.In the present protocol, the investigators will assess the effects of prefrontal tDCS on neurophysiological (i.e., electroencephalography - EEG - primary outcome) and behavioral (secondary outcome) measures in severely brain-injured patients with DOC in a double-blind sham-controlled design. One anodal and one sham tDCS will be delivered in a randomized order in chronic (>28 days post-onset) severely brain-damaged patients. The stimulation will have an intensity of 2 mA and will last 20 minutes. The anode will be placed on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region. Ten minutes of high-density EEG will be recorded using a 256-channel saline electrode net (Electrical Geodesics) directly before and after each tDCS session. Behavioral assessments will be performed using the Coma Recovery Scale-Revised before and after each session by an investigator blinded to the treatment allocation.

Official Title
-----------------
Prefontal tDCS in Patients With Disorders of Consciousness: Neurophysiological and Behavioural Outcomes

Conditions
-----------------
Vegetative State, Minimally Conscious State, Disorder of Consciousness

Intervention / Treatment
-----------------
* Device: anodal tDCS
* Device: sham tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: post-comatose patients patients in vegetative state/unresponsive wakefulness syndrome or in minimally conscious state patients with stable condition patients free of sedative drugs and Na+ or Ca++ blockers (e.g., carbamazepine) or NMDA receptor antagonist (e.g., dextromethorphan) Exclusion Criteria: premorbid neurology antecedent patients in coma patients < 28 days after the acute brain injury patients with a metallic cerebral implant/a shunt cranioplasty

Ages Eligible for Study
-----------------
Minimum Age: 16 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: anodal tDCS<br>Patients will receive anodal tDCS (left dorsolateral prefrontal stimulation) during 20 minutes preceded and followed by a clinical assessment (Coma Recovery Scale-Revised) and neurophysiological assessment (256 channels EEG). | Device: anodal tDCS<br>* Patients will receive anodal tDCS during 20 minutes preceded and followed by a behavioral assessment (Coma Recovery Scale Revised) and a high density EEG. The anode will be placed over F3 in order to stimulate the left dorsolateral prefrontal cortex and the cathode over the right supraorbital area.<br>|
| Placebo Comparator: sham tDCS<br>Patients will receive sham tDCS (15 secondes of stimulation) during 20 minutes preceded and followed by a clinical assessment (Coma Recovery Scale-Revised) and neurophysiological assessment (256 channels EEG). | Device: sham tDCS<br>* Identical to anodal tDCS, except that the stimulation will be stopped after 15 seconds.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the CRS-R scores | CRS-R will be performed before and after tDCS (anodal and sham). Comparison of the treatment effect (CRS-R total score after tDCS minus before) between real and sham tDCS | Baseline and directly after the tDCS (20 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in EEG | 256 channels EEG will be record before and after tDCS to record potential cortical changes induce by the stimulation. | Baseline and directly after the tDCS (20 minutes) | 
| Change in the vigilance level | Ocular parameters will be record using glasses before and after tDCS to record potential change of the vigilance level | Baseline and directly after the tDCS (20 minutes) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Vegetative state, Minimally Conscious State, Disorders of consciousness, Transcranial direct current stimulation, Non invasive brain stimulation, Neuromodulation, High density electroencephalography