<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/NCT03797573</url>
  </required_header>
  <id_info>
    <org_study_id>2014/280B</org_study_id>
    <nct_id>NCT03797573</nct_id>
  </id_info>
  <brief_title>Multichannel tDCS to Reduce Hypertonia in Patients With Prolonged DOC</brief_title>
  <official_title>Effects of Multichannel Transcranial Direct Current Stimulation to Reduce Hypertonia in Patients With Prolonged Disorders of Consciousness: a Pilot Study.</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>
      Previous studies showed that transcranial direct current stimulation (tDCS) transiently&#xD;
      improves performance of motor function in stroke patients, as well as decrease muscle&#xD;
      hypertonia. In severely brain injured patients with disorders of consciousness (DOC), a&#xD;
      single stimulation over the left dorsolateral prefrontal cortex has shown to improve&#xD;
      patients' sign of consciousness. Nevertheless, other brain areas could be stimulated in order&#xD;
      to manage other symptoms occurring in this population of patients, such as muscle hypertonia.&#xD;
      In this study, investigators will assess the effects of bilateral fronto-central tDCS on&#xD;
      spasticity as measured with the Modified Ashworth Scale (MAS) and on the Coma Recovery&#xD;
      Scale-Revised (CRS-R) scores in patients with DOC in a double-blind sham-controlled&#xD;
      experimental design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Following severe brain damage and coma, some patients may remain in a vegetative state (VS)&#xD;
      or minimally conscious state (MCS). At present, there are no evidence-based guidelines&#xD;
      regarding the treatment of patients with disorders of consciousness (DOC). A previous study&#xD;
      showed that a single stimulation (using transcranial direct current stimulation - tDCS) of&#xD;
      the left prefrontal cortex induces an behavioral improvement in some patients in DOC.&#xD;
      Nevertheless, patients with DOC suffer from other invalidating dysfunctions such as&#xD;
      spasticity (muscle hypertonia). In sroke patients, the inhibition of the motor cortex through&#xD;
      cathodes placed over the motor region showed to reduce spasticity.&#xD;
&#xD;
      In this study, investigators aim to assess the effect of single session of transcranial&#xD;
      direct current stimulation (tDCS) over right and left fronto-central areas (using 2 anodes&#xD;
      and 2 cathodes), on the level of hypertonia and the level of consciousness of patients with&#xD;
      DOC, in a double blind randomized sham controlled study. The anodes will be placed over F3&#xD;
      and F4, and the cathodes over C3 and C4.&#xD;
&#xD;
      tDCS is a form of safe non-invasive cortical stimulation, modulating cortical excitability&#xD;
      under the electrodes, via weak polarizing currents. It has been reported that anodal tDCS&#xD;
      transiently improves motor functions in healthy subjects and patients with stroke or&#xD;
      Parkinson's disease.&#xD;
&#xD;
      By reducing the activity of the motor cortex (cathodes) and increasing the activity of the&#xD;
      prefrontal cortex (anodes) we expect to observe a better motor function in patients with DOC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 20, 2014</start_date>
  <completion_date type="Actual">December 13, 2017</completion_date>
  <primary_completion_date type="Actual">June 28, 2014</primary_completion_date>
  <phase>Phase 1</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 MAS scores</measure>
    <time_frame>baseline and directly after tDCS (20 minutes)</time_frame>
    <description>Modified Ashworth Scale (MAS) will by assessed before and after tDCS (active and sham). Comparison of treatment effect (MAS score after tDCS minus before) between active and sham tDCS. The MAS is a 5 points scale going from 0 (no spasticity) and 5 (extreme spasticity).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in the CRS-R total score</measure>
    <time_frame>Baseline and directly after the tDCS (20 minutes)]</time_frame>
    <description>Coma Recovery Scale Revised (CRS-R) will be performed before and after tDCS (anodal and sham). Comparison of the treatment effect (CRS-R total score score after tDCS minus before) between real and sham tDCS. The CRS-R is 23 points scale with 6 sub-scales (lower scores refer to reflexes, while higher scores refer to more complex behaviors). The total score is the sum of the scores in the 6 sub-scales.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in brain oscillations</measure>
    <time_frame>Baseline and directly after the tDCS (20 minutes)</time_frame>
    <description>8 channels electroencephalography (EEG) will be record before and after tDCS to record potential cortical changes induce by the stimulation. EEG power will be compared in different bandwidths (delta, theta, alpha, beta).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Vegetative State</condition>
  <condition>Minimally Conscious State</condition>
  <condition>Spasticity, Muscle</condition>
  <condition>Disorder of Consciousness</condition>
  <arm_group>
    <arm_group_label>active tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients will receive tDCS (bilateral fronto-central stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sham tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Patients will receive sham tDCS (5 seconds of stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>tDCS</intervention_name>
    <description>tDCS will be applied during 20 minutes with a current of 1 mA preceded and followed by a behavioral assessments (Modified Ashworth Scale and Coma Recovery Scale Revised) and an EEG. The anodes will be placed over F3 and F4 and the cathodes over C3 and C4.</description>
    <arm_group_label>active tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>sham tDCS</intervention_name>
    <description>Indentical to the active tDCS, except that the stimulation is terminated after 5 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 minimally 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&#xD;
&#xD;
          -  cranioplasty&#xD;
&#xD;
          -  shunt&#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 of Liege</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <reference>
    <citation>Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.</citation>
    <PMID>24574549</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 3, 2019</study_first_submitted>
  <study_first_submitted_qc>January 4, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 9, 2019</study_first_posted>
  <last_update_submitted>January 4, 2019</last_update_submitted>
  <last_update_submitted_qc>January 4, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 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>transcranial direct current stimulation</keyword>
  <keyword>disorder of consciousness</keyword>
  <keyword>muscle hypertonia</keyword>
  <keyword>spasticity</keyword>
  <keyword>vegetative state</keyword>
  <keyword>minimally conscious state</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Consciousness Disorders</mesh_term>
    <mesh_term>Persistent Vegetative State</mesh_term>
    <mesh_term>Muscle Hypertonia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03797573
org study id: 2014/280B
nct id: NCT03797573
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
Previous studies showed that transcranial direct current stimulation (tDCS) transiently
      improves performance of motor function in stroke patients, as well as decrease muscle
      hypertonia. In severely brain injured patients with disorders of consciousness (DOC), a
      single stimulation over the left dorsolateral prefrontal cortex has shown to improve
      patients' sign of consciousness. Nevertheless, other brain areas could be stimulated in order
      to manage other symptoms occurring in this population of patients, such as muscle hypertonia.
      In this study, investigators will assess the effects of bilateral fronto-central tDCS on
      spasticity as measured with the Modified Ashworth Scale (MAS) and on the Coma Recovery
      Scale-Revised (CRS-R) scores in patients with DOC in a double-blind sham-controlled
      experimental design.
Following severe brain damage and coma, some patients may remain in a vegetative state (VS)
      or minimally conscious state (MCS). At present, there are no evidence-based guidelines
      regarding the treatment of patients with disorders of consciousness (DOC). A previous study
      showed that a single stimulation (using transcranial direct current stimulation - tDCS) of
      the left prefrontal cortex induces an behavioral improvement in some patients in DOC.
      Nevertheless, patients with DOC suffer from other invalidating dysfunctions such as
      spasticity (muscle hypertonia). In sroke patients, the inhibition of the motor cortex through
      cathodes placed over the motor region showed to reduce spasticity.

      In this study, investigators aim to assess the effect of single session of transcranial
      direct current stimulation (tDCS) over right and left fronto-central areas (using 2 anodes
      and 2 cathodes), on the level of hypertonia and the level of consciousness of patients with
      DOC, in a double blind randomized sham controlled study. The anodes will be placed over F3
      and F4, and the cathodes over C3 and C4.

      tDCS is a form of safe non-invasive cortical stimulation, modulating cortical excitability
      under the electrodes, via weak polarizing currents. It has been reported that anodal tDCS
      transiently improves motor functions in healthy subjects and patients with stroke or
      Parkinson's disease.

      By reducing the activity of the motor cortex (cathodes) and increasing the activity of the
      prefrontal cortex (anodes) we expect to observe a better motor function in patients with DOC.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in MAS scores
time frame: baseline and directly after tDCS (20 minutes)
description: Modified Ashworth Scale (MAS) will by assessed before and after tDCS (active and sham). Comparison of treatment effect (MAS score after tDCS minus before) between active and sham tDCS. The MAS is a 5 points scale going from 0 (no spasticity) and 5 (extreme spasticity).
measure: Change in the CRS-R total score
time frame: Baseline and directly after the tDCS (20 minutes)]
description: Coma Recovery Scale Revised (CRS-R) will be performed before and after tDCS (anodal and sham). Comparison of the treatment effect (CRS-R total score score after tDCS minus before) between real and sham tDCS. The CRS-R is 23 points scale with 6 sub-scales (lower scores refer to reflexes, while higher scores refer to more complex behaviors). The total score is the sum of the scores in the 6 sub-scales.
measure: Change in brain oscillations
time frame: Baseline and directly after the tDCS (20 minutes)
description: 8 channels electroencephalography (EEG) will be record before and after tDCS to record potential cortical changes induce by the stimulation. EEG power will be compared in different bandwidths (delta, theta, alpha, beta).
arm group label: active tDCS
arm group type: Active Comparator
description: Patients will receive tDCS (bilateral fronto-central stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).
arm group label: sham tDCS
arm group type: Sham Comparator
description: Patients will receive sham tDCS (5 seconds of stimulation) during 20 minutes preceded and followed by a clinical assessment (Modified Ashworth Scale and Coma Recovery Scale-Revised) and neurophysiological assessment (8 channels EEG).
intervention type: Device
intervention name: tDCS
description: tDCS will be applied during 20 minutes with a current of 1 mA preceded and followed by a behavioral assessments (Modified Ashworth Scale and Coma Recovery Scale Revised) and an EEG. The anodes will be placed over F3 and F4 and the cathodes over C3 and C4.
arm group label: active tDCS
intervention type: Device
intervention name: sham tDCS
description: Indentical to the active tDCS, except that the stimulation is terminated after 5 seconds.
arm group label: sham tDCS
criteria: 
gender: All
minimum age: 16 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: Belgium
citation: Thibaut A, Bruno MA, Ledoux D, Demertzi A, Laureys S. tDCS in patients with disorders of consciousness: sham-controlled randomized double-blind study. Neurology. 2014 Apr 1;82(13):1112-8. doi: 10.1212/WNL.0000000000000260. Epub 2014 Feb 26.
PMID: 24574549
responsible party type: Principal Investigator
investigator affiliation: University of Liege
investigator full name: Aurore Thibaut
investigator title: Principal Investigator
mesh term: Muscle Spasticity
mesh term: Consciousness Disorders
mesh term: Persistent Vegetative State
mesh term: Muscle Hypertonia
sharing ipd: No