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

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.

Study Overview

• Status: Completed
• Conditions: Disorder of Consciousness; Minimally Conscious State; Vegetative State
• Intervention / Treatment: Device: anodal tDCS; Device: sham tDCS

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.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Liege, Belgium, 4000
    • University Hospital of Liege

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 75 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: anodal tDCS; 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; 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.
Placebo Comparator: sham tDCS; 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; Identical to anodal tDCS, except that the stimulation will be stopped after 15 seconds.

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)

Collaborators and Investigators

• Sponsor: University of Liege

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): June 1, 2019
• Study Completion (Actual): June 1, 2019

Study Registration Dates

• First Submitted: January 29, 2019
• First Submitted That Met QC Criteria: January 29, 2019
• First Posted (Actual): January 30, 2019

Study Record Updates

• Last Update Posted (Actual): July 17, 2019
• Last Update Submitted That Met QC Criteria: July 16, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Neuromodulation; Disorders of consciousness; Minimally Conscious State; Transcranial direct current stimulation; Vegetative state; Non invasive brain stimulation; High density electroencephalography
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Brain Damage, Chronic; Unconsciousness; Disease; Consciousness Disorders; Persistent Vegetative State
• Other Study ID Numbers: 2013-296

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No