<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03823508</url>
  </required_header>
  <id_info>
    <org_study_id>2013-296</org_study_id>
    <nct_id>NCT03823508</nct_id>
  </id_info>
  <brief_title>Prefontal tDCS in Patients With Disorders of Consciousness: Neurophysiological and Behavioural Outcomes</brief_title>
  <official_title>Prefontal tDCS in Patients With Disorders of Consciousness: Neurophysiological and Behavioural Outcomes</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Liege</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Liege</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Non-invasive brain stimulations techniques have recently shown promising results in patients&#xD;
      with disorders. Notably, transcranial direct current stimulation (tDCS) applied over the left&#xD;
      dorsolateral prefrontal cortex has proved to be effective in improving signs of consciousness&#xD;
      in about 50% of patients in MCS either after a single stimulation or after repeated sessions.&#xD;
      However, brain mechanisms underlying tDCS effects remain poorly understood. Here we aim to&#xD;
      assess the effects of prefrontal tDCS on neurophysiological (i.e., electroencephalography -&#xD;
      EEG - primary outcome) and behavioral (secondary outcome) measures in severely brain-injured&#xD;
      patients with DOC.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently, therapeutic options for severely brain-injured patients with disorders of&#xD;
      consciousness (DOC), including patients in unresponsive wakefulness syndrome (UWS) and&#xD;
      minimally conscious state (MCS), are limited and still need to be improved to influence&#xD;
      long-term outcomes. Non-invasive brain stimulations (NIBS) techniques have recently shown&#xD;
      promising results in DOC. Notably, transcranial direct current stimulation (tDCS) applied&#xD;
      over the left dorsolateral prefrontal cortex has proved to be effective in improving signs of&#xD;
      consciousness in about 50% of patients in MCS either after a single stimulation or after&#xD;
      repeated sessions. However, brain mechanisms underlying tDCS effects remain poorly&#xD;
      understood.In the present protocol, the investigators will assess the effects of prefrontal&#xD;
      tDCS on neurophysiological (i.e., electroencephalography - EEG - primary outcome) and&#xD;
      behavioral (secondary outcome) measures in severely brain-injured patients with DOC in a&#xD;
      double-blind sham-controlled design. One anodal and one sham tDCS will be delivered in a&#xD;
      randomized order in chronic (&gt;28 days post-onset) severely brain-damaged patients. The&#xD;
      stimulation will have an intensity of 2 mA and will last 20 minutes. The anode will be placed&#xD;
      on the left dorsolateral prefrontal cortex and the cathode on the right supraorbital region.&#xD;
      Ten minutes of high-density EEG will be recorded using a 256-channel saline electrode net&#xD;
      (Electrical Geodesics) directly before and after each tDCS session. Behavioral assessments&#xD;
      will be performed using the Coma Recovery Scale-Revised before and after each session by an&#xD;
      investigator blinded to the treatment allocation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2018</start_date>
  <completion_date type="Actual">June 1, 2019</completion_date>
  <primary_completion_date type="Actual">June 1, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in the CRS-R scores</measure>
    <time_frame>Baseline and directly after the tDCS (20 minutes)</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in EEG</measure>
    <time_frame>Baseline and directly after the tDCS (20 minutes)</time_frame>
    <description>256 channels EEG will be record before and after tDCS to record potential cortical changes induce by the stimulation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the vigilance level</measure>
    <time_frame>Baseline and directly after the tDCS (20 minutes)</time_frame>
    <description>Ocular parameters will be record using glasses before and after tDCS to record potential change of the vigilance level</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Vegetative State</condition>
  <condition>Minimally Conscious State</condition>
  <condition>Disorder of Consciousness</condition>
  <arm_group>
    <arm_group_label>anodal tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>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).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham tDCS</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>anodal tDCS</intervention_name>
    <description>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.</description>
    <arm_group_label>anodal tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>sham tDCS</intervention_name>
    <description>Identical to anodal tDCS, except that the stimulation will be stopped after 15 seconds.</description>
    <arm_group_label>sham tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  post-comatose patients&#xD;
&#xD;
          -  patients in vegetative state/unresponsive wakefulness syndrome or in minimally&#xD;
             conscious state&#xD;
&#xD;
          -  patients with stable condition&#xD;
&#xD;
          -  patients free of sedative drugs and Na+ or Ca++ blockers (e.g., carbamazepine) or NMDA&#xD;
             receptor antagonist (e.g., dextromethorphan)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  premorbid neurology antecedent&#xD;
&#xD;
          -  patients in coma&#xD;
&#xD;
          -  patients &lt; 28 days after the acute brain injury&#xD;
&#xD;
          -  patients with a metallic cerebral implant/a shunt&#xD;
&#xD;
          -  cranioplasty&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>16 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>University Hospital of Liege</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>July 2019</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>January 29, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <last_update_submitted>July 16, 2019</last_update_submitted>
  <last_update_submitted_qc>July 16, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 17, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Liege</investigator_affiliation>
    <investigator_full_name>Aurore Thibaut</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Vegetative state</keyword>
  <keyword>Minimally Conscious State</keyword>
  <keyword>Disorders of consciousness</keyword>
  <keyword>Transcranial direct current stimulation</keyword>
  <keyword>Non invasive brain stimulation</keyword>
  <keyword>Neuromodulation</keyword>
  <keyword>High density electroencephalography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Consciousness Disorders</mesh_term>
    <mesh_term>Persistent Vegetative State</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03823508
org study id: 2013-296
nct id: NCT03823508
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in the CRS-R scores
time frame: Baseline and directly after the tDCS (20 minutes)
description: 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
measure: Change in EEG
time frame: Baseline and directly after the tDCS (20 minutes)
description: 256 channels EEG will be record before and after tDCS to record potential cortical changes induce by the stimulation.
measure: Change in the vigilance level
time frame: Baseline and directly after the tDCS (20 minutes)
description: Ocular parameters will be record using glasses before and after tDCS to record potential change of the vigilance level
arm group label: anodal tDCS
arm group type: Active Comparator
description: 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).
arm group label: sham tDCS
arm group type: Placebo Comparator
description: 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).
intervention type: Device
intervention name: anodal tDCS
description: 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.
arm group label: anodal tDCS
intervention type: Device
intervention name: sham tDCS
description: Identical to anodal tDCS, except that the stimulation will be stopped after 15 seconds.
arm group label: sham tDCS
criteria: 
gender: All
minimum age: 16 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Belgium
responsible party type: Principal Investigator
investigator affiliation: University of Liege
investigator full name: Aurore Thibaut
investigator title: Principal Investigator
mesh term: Consciousness Disorders
mesh term: Persistent Vegetative State