<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/NCT03007784</url>
  </required_header>
  <id_info>
    <org_study_id>SC20160427</org_study_id>
    <nct_id>NCT03007784</nct_id>
  </id_info>
  <brief_title>Two Intensities of Transcranial Direct Current Stimulation to Improve Consciousness in Severely Brain Injured Patients</brief_title>
  <acronym>STIMCOM</acronym>
  <sponsors>
    <lead_sponsor>
      <agency>Groupe Hospitalier Pitie-Salpetriere</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Hôpital Raymond Poincaré</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hospices Civils de Lyon</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Groupe Hospitalier Pitie-Salpetriere</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Limited treatments are available to improve consciousness in severely brain injured patients.&#xD;
      Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed&#xD;
      evidence of efficacy to increase level of consciousness and functional communication in some&#xD;
      minimally conscious state (MCS) patients, and in some vegetative state (VS) patients. However&#xD;
      the optimal intensity of electrical current stimulation remains unknown.&#xD;
&#xD;
      This study will test the effects of two intensities of tDCS stimulation (either 0.2mA or 2mA)&#xD;
      applied on left dorso-lateral prefrontal cortex on both behavior, - assessed by the Coma&#xD;
      Recovery Scale-Revised (CRS-R) scores -, as well as quantified EEG recorded during resting&#xD;
      state (using algorithms previously designed and published by the investigators) and&#xD;
      event-related potentials (using auditory paradigms we previously published) in severely brain&#xD;
      damaged patients with disorders of consciousness (MCS, VS, and conscious but cognitively&#xD;
      disabled patients) of various etiologies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will use a cross-over double-blind design with each patient receiving both current&#xD;
      intensities in a randomized order during 4 weeks (2 weeks for each tDCS intensity, totalizing&#xD;
      a number of 10X2 stimulation sessions of 20 minutes each).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <primary_completion_date type="Anticipated">January 2021</primary_completion_date>
  <phase>Phase 3</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 of the Coma Recovery Scale-Revised score according to tDCS current intensity (2mA versus 0.2mA)</measure>
    <time_frame>Last Day of 0.2mA session (Day 14th or Day 28th) versus Last Day of 2mA session (Day 14th or Day 28th)</time_frame>
    <description>Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at the tenth day of 2mA stimulation (Day14 or Day28)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of the Coma Recovery Scale-Revised score after 2mA tDCS current intensity</measure>
    <time_frame>Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Comparison of the CRS-R score at the tenth day of 2mA stimulation (Day14 or Day28) with the score at baselne (Day1)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline of the Coma Recovery Scale-Revised score after 0.2mA tDCS current intensity</measure>
    <time_frame>Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at baselne (Day1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>IChange of the ERPS recorded during the &quot;local global&quot; auditory paradigm (Bekinschtein et al., PNAS 2009) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity</measure>
    <time_frame>Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)</time_frame>
    <description>Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the ERPS recorded during the &quot;local global&quot; auditory paradigm (Bekinschtein et al., PNAS 2009) after 2mA tDCS current intensity</measure>
    <time_frame>Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 2mA tDCS stimulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the ERPS recorded during the &quot;local global&quot; auditory paradigm (Bekinschtein et al., PNAS 2009) after 0.2mA tDCS current intensity</measure>
    <time_frame>Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 0.2mA tDCS stimulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>IChange of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity</measure>
    <time_frame>Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)</time_frame>
    <description>Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity</measure>
    <time_frame>Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 0.2mA tDCS current intensity</measure>
    <time_frame>Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)</time_frame>
    <description>Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">300</enrollment>
  <condition>Disorder of Consciousness</condition>
  <condition>Minimally Conscious State</condition>
  <condition>Vegetative State</condition>
  <condition>Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>2 mA anodal tDCS stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anodal tDCS stimulation at 2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0.2 mA anodal tDCS stimulation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Anodal tDCS stimulation at 0.2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>transcranial direct current stimulation (tDCS) / Comparison of current intensities</intervention_name>
    <arm_group_label>0.2 mA anodal tDCS stimulation</arm_group_label>
    <arm_group_label>2 mA anodal tDCS stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Non communicative patients (including conscious patients but presenting with major&#xD;
             fluctuations of vigilance and/or of cognitive abilities)&#xD;
&#xD;
          -  Patients with stable clinical examination&#xD;
&#xD;
          -  Age between 18 and 80 years&#xD;
&#xD;
          -  Brain injury confirmed by cerebral imaging (MRI or TDM)&#xD;
&#xD;
          -  Disorder of consciousness diagnosed by CRS-R (VS, MCS, exitMCS)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Status epilepticus&#xD;
&#xD;
          -  Severely neurodegenerative illnesses (Alzheimer disease, Lewy Body Dementia)&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Patients underage&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lionel Naccache, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>Paris 6 University ICM Inserm APHP</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jacobo Sitt, MD PhD</last_name>
    <phone>+33 1 57 27 43 17</phone>
    <email>jacobo.sitt@icm-institute.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bertrand Hermann, MD Msc</last_name>
    <phone>+33 1 57 27 43 14</phone>
    <email>bertrand.hermann@icm-institute.org</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Groupe Hospitalier Pitié-Salpêtrière</name>
      <address>
        <city>Paris</city>
        <zip>75013</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lionel Naccache, MD, PhD</last_name>
      <phone>+33157274314</phone>
      <email>lionel.naccache@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>January 2017</verification_date>
  <study_first_submitted>December 22, 2016</study_first_submitted>
  <study_first_submitted_qc>December 28, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 2, 2017</study_first_posted>
  <last_update_submitted>January 14, 2017</last_update_submitted>
  <last_update_submitted_qc>January 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Groupe Hospitalier Pitie-Salpetriere</investigator_affiliation>
    <investigator_full_name>LIONEL NACCACHE</investigator_full_name>
    <investigator_title>MD, PhD</investigator_title>
  </responsible_party>
  <keyword>Consciousness</keyword>
  <keyword>Disorder of consciousness</keyword>
  <keyword>Minimally conscious state</keyword>
  <keyword>Vegetative state</keyword>
  <keyword>Exit-MCS</keyword>
  <keyword>Transcranial direct current stimulation (tDCS)</keyword>
  <keyword>CRS-R</keyword>
  <keyword>EEG</keyword>
  <keyword>Cognitive ERPs</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/NCT03007784
org study id: SC20160427
nct id: NCT03007784
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
Limited treatments are available to improve consciousness in severely brain injured patients.
      Transcranial Direct Current stimulation (tDCS) is one of the few therapeutics that showed
      evidence of efficacy to increase level of consciousness and functional communication in some
      minimally conscious state (MCS) patients, and in some vegetative state (VS) patients. However
      the optimal intensity of electrical current stimulation remains unknown.

      This study will test the effects of two intensities of tDCS stimulation (either 0.2mA or 2mA)
      applied on left dorso-lateral prefrontal cortex on both behavior, - assessed by the Coma
      Recovery Scale-Revised (CRS-R) scores -, as well as quantified EEG recorded during resting
      state (using algorithms previously designed and published by the investigators) and
      event-related potentials (using auditory paradigms we previously published) in severely brain
      damaged patients with disorders of consciousness (MCS, VS, and conscious but cognitively
      disabled patients) of various etiologies.
This study will use a cross-over double-blind design with each patient receiving both current
      intensities in a randomized order during 4 weeks (2 weeks for each tDCS intensity, totalizing
      a number of 10X2 stimulation sessions of 20 minutes each).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change of the Coma Recovery Scale-Revised score according to tDCS current intensity (2mA versus 0.2mA)
time frame: Last Day of 0.2mA session (Day 14th or Day 28th) versus Last Day of 2mA session (Day 14th or Day 28th)
description: Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at the tenth day of 2mA stimulation (Day14 or Day28)
measure: Change from baseline of the Coma Recovery Scale-Revised score after 2mA tDCS current intensity
time frame: Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Comparison of the CRS-R score at the tenth day of 2mA stimulation (Day14 or Day28) with the score at baselne (Day1)
measure: Change from baseline of the Coma Recovery Scale-Revised score after 0.2mA tDCS current intensity
time frame: Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Comparison of the CRS-R score at the tenth day of 0.2mA stimulation (Day14 or Day28) with the score at baselne (Day1)
measure: IChange of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity
time frame: Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)
description: Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)
measure: Change from baseline of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 2mA tDCS current intensity
time frame: Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 2mA tDCS stimulation
measure: Change from baseline of the ERPS recorded during the "local global" auditory paradigm (Bekinschtein et al., PNAS 2009) after 0.2mA tDCS current intensity
time frame: Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Statistical comparison of local (MMN, automatic CNV) and global (P3b; modulation of CNV) ERP effects recorded at baseline (Day 1) and after 10 days of 0.2mA tDCS stimulation
measure: IChange of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity and after 10 days of 0.2mA tDCS current intensity
time frame: Last Day of 2mA session (Day 14th or Day 28th) versus Last Day of 0.2mA session (Day 14th or Day 28th)
description: Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)
measure: Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 2mA tDCS current intensity
time frame: Last Day of 2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th)
measure: Change from baseline of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain et al. 2014) after 10 days of 0.2mA tDCS current intensity
time frame: Last Day of 0.2mA session (Day 14th or Day 28th) versus baseline (Day 1st)
description: Statistical comparison of the multivariate automatic classification of conscious state from EEG (Sitt et al., Brain 2014) at baseline (Day 1st) and after 10 days of 2mA tDCS stimulation (Day 14th or Day 28th) and after 10 days of 0.2mA tDCS stimulation (Day 14th or Day 28th)
arm group label: 2 mA anodal tDCS stimulation
arm group type: Experimental
description: Anodal tDCS stimulation at 2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks
arm group label: 0.2 mA anodal tDCS stimulation
arm group type: Active Comparator
description: Anodal tDCS stimulation at 0.2 mA applied to the left dorsolateral prefrontal during 20 minutes five days a week for two consecutive weeks
intervention type: Device
intervention name: transcranial direct current stimulation (tDCS) / Comparison of current intensities
arm group label: 0.2 mA anodal tDCS stimulation
arm group label: 2 mA anodal tDCS stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Lionel Naccache, MD PhD
role: Study Director
affiliation: Paris 6 University ICM Inserm APHP
last name: Jacobo Sitt, MD PhD
phone: +33 1 57 27 43 17
email: jacobo.sitt@icm-institute.org
last name: Bertrand Hermann, MD Msc
phone: +33 1 57 27 43 14
email: bertrand.hermann@icm-institute.org
facility: 
status: Recruiting
contact: 
country: France
responsible party type: Principal Investigator
investigator affiliation: Groupe Hospitalier Pitie-Salpetriere
investigator full name: LIONEL NACCACHE
investigator title: MD, PhD
mesh term: Consciousness Disorders
mesh term: Persistent Vegetative State