<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/NCT04401319</url>
  </required_header>
  <id_info>
    <org_study_id>B0201941888</org_study_id>
    <nct_id>NCT04401319</nct_id>
  </id_info>
  <brief_title>rTMS and EEG in DOC Patients</brief_title>
  <official_title>Repetitive Transcranial Magnetic Stimulation and Electroencephalography in Patients With Disorders of Consciousness</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Liege</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Therapiezentrum Burgau</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </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>
      Background:&#xD;
&#xD;
      Severe brain injury could cause chronic disorders of consciousness (DOC). Treating DOC&#xD;
      patients to improve recovery remains very challenging. A few randomized controlled studies&#xD;
      have been published in the recent years, focusing on non-invasive brain stimulation (NIBS)&#xD;
      treatments to improve patients' neurobehavioural functioning. Among NIBS, repetitive&#xD;
      transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that&#xD;
      can modulate cortical excitability, enhance neural plasticity, and induce strong&#xD;
      neuromodulatory effects that outlast the period of stimulation. It is thought to modulate&#xD;
      cortical activity and could therefore be effective for treating DOC patients. Currently,&#xD;
      there is no unified protocol for rTMS in DOC patients and studies vary in many aspects.&#xD;
&#xD;
      In this study, the investigators aim to improve the functional recovery of DOC patients&#xD;
      following severe brain injury using rTMS in two multi-center double-blind studies.&#xD;
&#xD;
      Methods/design:&#xD;
&#xD;
      The investigators will recruit 90 DOC patients. Patients will have three rTMS sessions that&#xD;
      will be randomized within patients in a crossover design: (i) one real stimulation on the&#xD;
      left dorsolateral prefrontal cortex (DLPFC); (ii) one real stimulation on the left angular&#xD;
      cortex (AG) and (iii) one sham stimulation. Sessions will be separated by at least 5 days&#xD;
      washout period. Each stimulation session will last 20 minutes with a frequency of 20Hz (train&#xD;
      duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold -&#xD;
      RMT). The RMT, i.e., the minimum stimulus intensity that generated a motor evoked potential&#xD;
      response of at least 50μV at rest for 5 out of 10 trials, will be calculated for the&#xD;
      stimulation target using single-pulses on the right abductor pollicis brevis muscle.&#xD;
&#xD;
      After an interval of one week, a parallel design study will begin. Ninety patients will be&#xD;
      randomly divided in two experimental groups and one sham group (30 patients per group).&#xD;
      Stimulation will be performed for 20 working days once a day with the same stimulation&#xD;
      parameters as in the crossover study.&#xD;
&#xD;
      Primary outcome will be determined as behavioral response to treatment as measured using the&#xD;
      Coma Recovery Scale - Revised (CRS-R). Resting-state high-density EEG will be also recorded&#xD;
      to investigate the neurophysiological correlates by rTMS.&#xD;
&#xD;
      Discussion:&#xD;
&#xD;
      This study will contribute to define the role of rTMS for the treatment of DOC patients and&#xD;
      characterise the neural correlates of its action. In addition, the investigators will define&#xD;
      the responders' profile based on patients' characteristics and functional impairments and&#xD;
      develop biomarkers of responsiveness using machine learning to categorize EEG signals&#xD;
      according to clinical responsiveness to the treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">September 2023</start_date>
  <completion_date type="Anticipated">January 2025</completion_date>
  <primary_completion_date type="Anticipated">November 2024</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>Sequential Assignment</intervention_model>
    <intervention_model_description>We will perform a 3 arm crossover trial. Subsequently, we will perform a longer protocol using a 3 arm parallel design.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline Coma Recovery Scale - Revised for Crossover Study</measure>
    <time_frame>immediately after each rTMS session</time_frame>
    <description>The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Coma Recovery Scale - Revised for Parallel Study 1</measure>
    <time_frame>immediately after the last rTMS session</time_frame>
    <description>The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Coma Recovery Scale - Revised for Parallel Study 2</measure>
    <time_frame>1 week after the last rTMS session</time_frame>
    <description>The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Coma Recovery Scale - Revised for Parallel Study 3</measure>
    <time_frame>2 week after the last rTMS session</time_frame>
    <description>The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Resting-State EEG for Crossover Study 1</measure>
    <time_frame>during each rTMS session</time_frame>
    <description>EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Resting-State EEG for Crossover Study 2</measure>
    <time_frame>immediately after each rTMS session</time_frame>
    <description>EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Resting-State EEG for Parallel Study 1</measure>
    <time_frame>immediately after the last rTMS session</time_frame>
    <description>EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Resting-State EEG for Parallel Study 2</measure>
    <time_frame>1 week after the last rTMS session</time_frame>
    <description>EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Resting-State EEG for Parallel Study 3</measure>
    <time_frame>2 week after the last rTMS session</time_frame>
    <description>EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Disorder of Consciousness</condition>
  <arm_group>
    <arm_group_label>Sham Stimulation Group for Crossover Study (DLPFC + AG)</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) and on the angular cortex (AG) using a sham coil in the crossover study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DLPFC Stimulation Group for Crossover Study</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the crossover study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AG Stimulation Group for Crossover Study</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the crossover study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham Stimulation Group for Parallel Study (DLPFC + AG)</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or on the angular cortex (AG) using a sham coil in the parallel study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>DLPFC Stimulation Group for Parallel Study</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the parallel study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>AG Stimulation Group for Parallel Study</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the parallel study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Stimulation for Crossover Study</intervention_name>
    <description>Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.</description>
    <arm_group_label>Sham Stimulation Group for Crossover Study (DLPFC + AG)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>DLPFC Stimulation for Crossover Study</intervention_name>
    <description>Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.</description>
    <arm_group_label>DLPFC Stimulation Group for Crossover Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AG Stimulation for Crossover Study</intervention_name>
    <description>Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.</description>
    <arm_group_label>AG Stimulation Group for Crossover Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham Stimulation for Parallel Study</intervention_name>
    <description>Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.</description>
    <arm_group_label>Sham Stimulation Group for Parallel Study (DLPFC + AG)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>DLPFC Stimulation for Parallel Study</intervention_name>
    <description>Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.</description>
    <arm_group_label>DLPFC Stimulation Group for Parallel Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>AG Stimulation for Parallel Study</intervention_name>
    <description>Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.</description>
    <arm_group_label>AG Stimulation Group for Parallel Study</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  over 18 years old&#xD;
&#xD;
          -  &gt; 28 days post-injury&#xD;
&#xD;
          -  patients with DOC due to acquired brain lesions classified according to international&#xD;
             guidelines as UWS or MCS with repeated behavioural assessments with the CRS-R&#xD;
&#xD;
          -  stable vital parameters&#xD;
&#xD;
          -  no previous neurological deficits anterior to the brain lesions&#xD;
&#xD;
          -  no pregnancy&#xD;
&#xD;
          -  no contraindication for rTMS or EEG (e.g., uncontrolled epilepsy, that is, seizure&#xD;
             within 4 weeks prior to enrollment, metallic implant in the skull, pacemaker,&#xD;
             craniotomy under the stimulated site, implanted brain device, sensitive skin)&#xD;
&#xD;
          -  no sedative drugs and drugs thought to interfere with brain stimulation such as Na or&#xD;
             Ca channel blockers (e.g., carbamazepine) or NMDA receptor antagonists (e.g.,&#xD;
             dextromethorphan)&#xD;
&#xD;
          -  no drugs or substances which have strong potential of seizure induction (imipramine,&#xD;
             amitriptyline, doxepin, nortriptyline, maprotiline, chlorpromazine, clozapine,&#xD;
             foscarnet, ganciclovir, ritonavir, amphetamines, cocaine, phencyclidine, ketamine,&#xD;
             gamma-hydroxybutyrate, alcohol, and theophylline).&#xD;
&#xD;
          -  All etiologies (e.g., trauma, stroke, and anoxia)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Masachika Niimi, M.D., Ph.D.</last_name>
    <phone>+32494999230</phone>
    <email>m.niimi@uliege.be</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Olivia Gosseries, Ph.D.</last_name>
    <phone>+3243663954</phone>
    <email>ogosseries@uliege.be</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University Hospital of Liège</name>
      <address>
        <city>Liège</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
    <contact>
      <last_name>Masachika Niimi, M.D., Ph.D.</last_name>
      <phone>+32494999230</phone>
      <email>m.niimi@uliege.be</email>
    </contact>
    <contact_backup>
      <last_name>Olivia Gosseries, Ph.D.</last_name>
      <phone>+3243663954</phone>
      <email>ogosseries@uliege.be</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Therapiezentrum Burgau</name>
      <address>
        <city>Burgau</city>
        <zip>89331</zip>
        <country>Germany</country>
      </address>
    </facility>
    <contact>
      <last_name>Martin Rosenfelder, MSc</last_name>
      <phone>+498222404138</phone>
      <email>m.rosenfelder@therapiezentrum-burgau.de</email>
    </contact>
    <contact_backup>
      <last_name>Andreas Bender, M.D., Ph.D.</last_name>
    </contact_backup>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>May 3, 2020</study_first_submitted>
  <study_first_submitted_qc>May 19, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 26, 2020</study_first_posted>
  <last_update_submitted>June 21, 2023</last_update_submitted>
  <last_update_submitted_qc>June 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Liege</investigator_affiliation>
    <investigator_full_name>Olivia Gosseries</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>disorders of consciousness</keyword>
  <keyword>transcranial magnetic stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Consciousness Disorders</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/NCT04401319
org study id: B0201941888
nct id: NCT04401319
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Background:

      Severe brain injury could cause chronic disorders of consciousness (DOC). Treating DOC
      patients to improve recovery remains very challenging. A few randomized controlled studies
      have been published in the recent years, focusing on non-invasive brain stimulation (NIBS)
      treatments to improve patients' neurobehavioural functioning. Among NIBS, repetitive
      transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that
      can modulate cortical excitability, enhance neural plasticity, and induce strong
      neuromodulatory effects that outlast the period of stimulation. It is thought to modulate
      cortical activity and could therefore be effective for treating DOC patients. Currently,
      there is no unified protocol for rTMS in DOC patients and studies vary in many aspects.

      In this study, the investigators aim to improve the functional recovery of DOC patients
      following severe brain injury using rTMS in two multi-center double-blind studies.

      Methods/design:

      The investigators will recruit 90 DOC patients. Patients will have three rTMS sessions that
      will be randomized within patients in a crossover design: (i) one real stimulation on the
      left dorsolateral prefrontal cortex (DLPFC); (ii) one real stimulation on the left angular
      cortex (AG) and (iii) one sham stimulation. Sessions will be separated by at least 5 days
      washout period. Each stimulation session will last 20 minutes with a frequency of 20Hz (train
      duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold -
      RMT). The RMT, i.e., the minimum stimulus intensity that generated a motor evoked potential
      response of at least 50μV at rest for 5 out of 10 trials, will be calculated for the
      stimulation target using single-pulses on the right abductor pollicis brevis muscle.

      After an interval of one week, a parallel design study will begin. Ninety patients will be
      randomly divided in two experimental groups and one sham group (30 patients per group).
      Stimulation will be performed for 20 working days once a day with the same stimulation
      parameters as in the crossover study.

      Primary outcome will be determined as behavioral response to treatment as measured using the
      Coma Recovery Scale - Revised (CRS-R). Resting-state high-density EEG will be also recorded
      to investigate the neurophysiological correlates by rTMS.

      Discussion:

      This study will contribute to define the role of rTMS for the treatment of DOC patients and
      characterise the neural correlates of its action. In addition, the investigators will define
      the responders' profile based on patients' characteristics and functional impairments and
      develop biomarkers of responsiveness using machine learning to categorize EEG signals
      according to clinical responsiveness to the treatment.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: We will perform a 3 arm crossover trial. Subsequently, we will perform a longer protocol using a 3 arm parallel design.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change from Baseline Coma Recovery Scale - Revised for Crossover Study
time frame: immediately after each rTMS session
description: The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
measure: Change from Baseline Coma Recovery Scale - Revised for Parallel Study 1
time frame: immediately after the last rTMS session
description: The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
measure: Change from Baseline Coma Recovery Scale - Revised for Parallel Study 2
time frame: 1 week after the last rTMS session
description: The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
measure: Change from Baseline Coma Recovery Scale - Revised for Parallel Study 3
time frame: 2 week after the last rTMS session
description: The Coma Recovery Scale - Revised is a non-invasive behavioural examination. It contains 23 items hierarchically presented and divided in 6 sub-scales (auditory, visual, motor, oro-motor/verbal, communication and arousal). The score is based on presence or absence of behaviours in response to sensory stimulations. The quantitative score can be calculated by adding the best observed response in each sub-scale. The diagnosis is obtained from the quality of observed behaviours (e.g., the ability of visual tracking means that the patient is minimally conscious). The total score ranges between 0 and 23. Higher scores mean a better outcome.
measure: Change from Baseline Resting-State EEG for Crossover Study 1
time frame: during each rTMS session
description: EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.
measure: Change from Baseline Resting-State EEG for Crossover Study 2
time frame: immediately after each rTMS session
description: EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.
measure: Change from Baseline Resting-State EEG for Parallel Study 1
time frame: immediately after the last rTMS session
description: EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.
measure: Change from Baseline Resting-State EEG for Parallel Study 2
time frame: 1 week after the last rTMS session
description: EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.
measure: Change from Baseline Resting-State EEG for Parallel Study 3
time frame: 2 week after the last rTMS session
description: EEG will be collected using a high-density EEG. Fifteen minutes of resting state will be performed. Resting-state EEG complexity and connectivity analyses will be performed at the individual and group level. The investigators will compute spectral measures as well as cortical functional connectivity using median spectral connectivity and graph-theoretic topology metrics such as clustering coefficient, path length, modularity and participation coefficient.
arm group label: Sham Stimulation Group for Crossover Study (DLPFC + AG)
arm group type: Sham Comparator
description: Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) and on the angular cortex (AG) using a sham coil in the crossover study.
arm group label: DLPFC Stimulation Group for Crossover Study
arm group type: Active Comparator
description: Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the crossover study.
arm group label: AG Stimulation Group for Crossover Study
arm group type: Active Comparator
description: Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the crossover study.
arm group label: Sham Stimulation Group for Parallel Study (DLPFC + AG)
arm group type: Sham Comparator
description: Sham stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or on the angular cortex (AG) using a sham coil in the parallel study.
arm group label: DLPFC Stimulation Group for Parallel Study
arm group type: Active Comparator
description: Real stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil in the parallel study.
arm group label: AG Stimulation Group for Parallel Study
arm group type: Active Comparator
description: Real stimulation will be delivered on the left angular cortex (AG) using a real coil in the parallel study.
intervention type: Device
intervention name: Sham Stimulation for Crossover Study
description: Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.
arm group label: Sham Stimulation Group for Crossover Study (DLPFC + AG)
intervention type: Device
intervention name: DLPFC Stimulation for Crossover Study
description: Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.
arm group label: DLPFC Stimulation Group for Crossover Study
intervention type: Device
intervention name: AG Stimulation for Crossover Study
description: Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. A single session will be conducted.
arm group label: AG Stimulation Group for Crossover Study
intervention type: Device
intervention name: Sham Stimulation for Parallel Study
description: Stimulation will be delivered on the dorsolateral prefrontal cortex (DLPFC) or the angular cortex (AG) using a sham coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.
arm group label: Sham Stimulation Group for Parallel Study (DLPFC + AG)
intervention type: Device
intervention name: DLPFC Stimulation for Parallel Study
description: Stimulation will be delivered on the left dorsolateral prefrontal cortex (DLPFC) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.
arm group label: DLPFC Stimulation Group for Parallel Study
intervention type: Device
intervention name: AG Stimulation for Parallel Study
description: Stimulation will be delivered on the left angular cortex (AG) using a real coil for 20 minutes with a frequency of 20Hz (train duration: 4s; inter-train interval: 26s; 3200 pulses at 80% of the resting motor threshold ) in one session. Twenty sessions will be conducted.
arm group label: AG Stimulation Group for Parallel Study
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Masachika Niimi, M.D., Ph.D.
phone: +32494999230
email: m.niimi@uliege.be
last name: Olivia Gosseries, Ph.D.
phone: +3243663954
email: ogosseries@uliege.be
facility: 
contact: 
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country: Belgium
country: Germany
responsible party type: Principal Investigator
investigator affiliation: University of Liege
investigator full name: Olivia Gosseries
investigator title: Principal Investigator
mesh term: Consciousness Disorders