<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/NCT02222012</url>
  </required_header>
  <id_info>
    <org_study_id>sha-04-14</org_study_id>
    <nct_id>NCT02222012</nct_id>
  </id_info>
  <brief_title>Neuromarkers Identification in Major Depressive Disorder Based on Monitoring Measures</brief_title>
  <official_title>Identification of Neuromarkers in Novel Neuromodulation Treatment in Major Depressive Disorder Based on Integration of Multiple Monitoring Measures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shalvata Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Beer Yaakov Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shalvata Mental Health Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators propose a multi-source pattern which integrates neuroimaging data&#xD;
      associated with multiple, symptom-related neural processes relevant in depression to improve&#xD;
      classification accuracy. The investigators conclude that combining brain activation related&#xD;
      to the core-symptoms of depression using the multi-source monitoring data substantially&#xD;
      increases classification accuracy while providing a sparse relational neuromarkers-model for&#xD;
      future prediction.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.) is a novel TMS stimulator with several new&#xD;
      and unique properties. Currently standard TMS devices include a single channel, and can&#xD;
      operate only a single coil. The &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.) includes two&#xD;
      channels which can operate two independent TMS coils, either simultaneously or sequentially.&#xD;
&#xD;
      The &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.) may be used to obtain a differential&#xD;
      activation of various brain regions. For instance it can be used to induce high frequency&#xD;
      stimulation of a certain brain region, thus inducing facilitation, while simultaneously&#xD;
      stimulate at low frequency in another brain region, leading to inhibition.&#xD;
&#xD;
      In the current study the investigators propose a multi-source pattern which integrates&#xD;
      neuroimaging data associated with multiple, symptom-related neural processes relevant in&#xD;
      depression to improve classification accuracy. The investigators conclude that combining&#xD;
      brain activation related to the core-symptoms of depression using the multi-source monitoring&#xD;
      data substantially increases classification accuracy while providing a sparse relational&#xD;
      neuromarkers-model for future prediction.&#xD;
&#xD;
      The purpose of the study is to to monitor and optimize the anti depressive effect of brain&#xD;
      modulation technique using novel multi model monitoring approach.&#xD;
&#xD;
      Subjects will be treated with one of two designs of the study device (the &quot;Multiway Coil®&quot;):&#xD;
&#xD;
        1. Single Channel with a coil placed over the left PFC (10 Hz).&#xD;
&#xD;
        2. Two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC.&#xD;
&#xD;
      All subjects in the current study will undergo monitoring procedure inclusive of functional&#xD;
      MRI and electroencephalogram.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>August 2014</start_date>
  <completion_date type="Anticipated">September 2017</completion_date>
  <primary_completion_date type="Anticipated">September 2014</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>Parallel Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Clinical antidepressant response as defined by decline of HDRS-21 score over time</measure>
    <time_frame>20 day</time_frame>
    <description>Clinical antidepressant response at the end of the treatment, defined as a decline in Hamilton depression rating scale (HDRS-21) from the baseline rating by 50%.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Symptomatic improvement</measure>
    <time_frame>day 20</time_frame>
    <description>Symptomatic improvement at the 4-week end point as measured with Hamilton Anxiety Rating Scale ( HARS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical antidepressant remission as defined by decline of HDRS-21 score over time</measure>
    <time_frame>Day 20</time_frame>
    <description>Clinical antidepressant remission at the end of the treatment, defined as exit Hamilton Depression Rating Scale &lt;10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptomatic improvement</measure>
    <time_frame>day 20</time_frame>
    <description>Symptomatic improvement at the 4-week end point as measured with Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Symptomatic improvement</measure>
    <time_frame>day 20</time_frame>
    <description>Symptomatic improvement at the 4-week end point as measured with Clinical Global Impression (CGI)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>single channel</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Two channels &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>single channel &quot;Multiway Coil®&quot;</intervention_name>
    <description>During the single channel treatment trial period the patients will receive the following dose of rTMS: 10 Hz - left DLPFC ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks).</description>
    <arm_group_label>single channel</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Two channels &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.)</intervention_name>
    <description>During the two channels treatment trial period the patients will receive the following dose of rTMS: 10 Hz- left DLPFC, 1Hz - right DLPFC together.&#xD;
10 Hz protocol: ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks)&#xD;
1 Hz protocol:&#xD;
1 Hz, at 120% MT, 5 min pulse train, 1 min inter-train interval, 6 trains, i.e. a total of 1800 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 36,000 pulses in 4 weeks).</description>
    <arm_group_label>Two channels &quot;Multiway stimulator coil®&quot; (Brainsway Ltd.)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Outpatient&#xD;
&#xD;
          -  Diagnosed by senior psychiatrist as suffering from major depression episode according&#xD;
             to DSM IV using the Structured Clinical Interview for DSM-4 (SCID).&#xD;
&#xD;
          -  Rating on HDRS-21&gt;20.&#xD;
&#xD;
          -  Age: 18-68 years.&#xD;
&#xD;
          -  Treated for the current depressive episode, at least four weeks, with at least one&#xD;
             antidepressant in accepted dose, without improvement, according to their medical chart&#xD;
             and ATHF ( antidepressant treatment history form) instruction guidelines .&#xD;
&#xD;
          -  Gave informed consent for participation in the study.&#xD;
&#xD;
          -  Negative answers on safety screening questionnaire for transcranial magnetic&#xD;
             stimulation.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis as suffering from other diagnosis on axis 1 ( like: schizophrenia, bipolar&#xD;
             disorder, psychotic depression, geriatric depression).&#xD;
&#xD;
          -  Diagnosis as suffering from Severe Borderline Personality Disorder or hospitalized due&#xD;
             to exacerbation related to of borderline personality disorder.&#xD;
&#xD;
          -  Substantial suicidal risk as judged by the treating psychiatrist.&#xD;
&#xD;
          -  Attempted suicide in the past year.&#xD;
&#xD;
          -  Any current unstable medical or surgical illness.&#xD;
&#xD;
          -  History of seizure or heat convulsion.&#xD;
&#xD;
          -  History of epilepsy or seizure in first degree relatives.&#xD;
&#xD;
          -  History of head injury.&#xD;
&#xD;
          -  History of any metal in the head (outside the mouth).&#xD;
&#xD;
          -  Known history of any metallic particles in the eye, implanted cardiac pacemaker or any&#xD;
             intracardiac lines, implanted neurostimulators, surgical clips, cochlear implants or&#xD;
             any medical pumps.&#xD;
&#xD;
          -  History of hearing loss.&#xD;
&#xD;
          -  History of drug abuse or alcoholism in the last 6 month.&#xD;
&#xD;
          -  Pregnancy or not using a reliable method of birth control.&#xD;
&#xD;
          -  Systematic and metabolic unstable disorders.&#xD;
&#xD;
          -  Inadequate communication with the patient.&#xD;
&#xD;
          -  Under custodial care.&#xD;
&#xD;
          -  Participation in current clinical study or clinical study within 30 days prior to this&#xD;
             study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuval Bloch, Md, Phd</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shalvata Mental Health Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yuval Bloch, MD, Phd</last_name>
    <phone>097478644</phone>
    <email>yuvalbl@clalit.org.il</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shalvata Mental Health Center</name>
      <address>
        <city>Hod-HaSharon</city>
        <country>Israel</country>
      </address>
    </facility>
    <contact>
      <last_name>Yechiel MD Levkovitz, Phd</last_name>
    </contact>
    <investigator>
      <last_name>Yuval Bloch, MD Phd</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Israel</country>
  </location_countries>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 17, 2014</study_first_submitted>
  <study_first_submitted_qc>August 20, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 21, 2014</study_first_posted>
  <last_update_submitted>August 20, 2014</last_update_submitted>
  <last_update_submitted_qc>August 20, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 21, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</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/NCT02222012
org study id: sha-04-14
nct id: NCT02222012
lead sponsor: 
collaborator: 
has dmc: Yes
The investigators propose a multi-source pattern which integrates neuroimaging data
      associated with multiple, symptom-related neural processes relevant in depression to improve
      classification accuracy. The investigators conclude that combining brain activation related
      to the core-symptoms of depression using the multi-source monitoring data substantially
      increases classification accuracy while providing a sparse relational neuromarkers-model for
      future prediction.
The "Multiway stimulator coil®" (Brainsway Ltd.) is a novel TMS stimulator with several new
      and unique properties. Currently standard TMS devices include a single channel, and can
      operate only a single coil. The "Multiway stimulator coil®" (Brainsway Ltd.) includes two
      channels which can operate two independent TMS coils, either simultaneously or sequentially.

      The "Multiway stimulator coil®" (Brainsway Ltd.) may be used to obtain a differential
      activation of various brain regions. For instance it can be used to induce high frequency
      stimulation of a certain brain region, thus inducing facilitation, while simultaneously
      stimulate at low frequency in another brain region, leading to inhibition.

      In the current study the investigators propose a multi-source pattern which integrates
      neuroimaging data associated with multiple, symptom-related neural processes relevant in
      depression to improve classification accuracy. The investigators conclude that combining
      brain activation related to the core-symptoms of depression using the multi-source monitoring
      data substantially increases classification accuracy while providing a sparse relational
      neuromarkers-model for future prediction.

      The purpose of the study is to to monitor and optimize the anti depressive effect of brain
      modulation technique using novel multi model monitoring approach.

      Subjects will be treated with one of two designs of the study device (the "Multiway Coil®"):

        1. Single Channel with a coil placed over the left PFC (10 Hz).

        2. Two channels: a. 10 Hz over the left PFC. b. 1 Hz over the right PFC.

      All subjects in the current study will undergo monitoring procedure inclusive of functional
      MRI and electroencephalogram.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Diagnostic
masking: None (Open Label)
measure: Clinical antidepressant response as defined by decline of HDRS-21 score over time
time frame: 20 day
description: Clinical antidepressant response at the end of the treatment, defined as a decline in Hamilton depression rating scale (HDRS-21) from the baseline rating by 50%.
measure: Symptomatic improvement
time frame: day 20
description: Symptomatic improvement at the 4-week end point as measured with Hamilton Anxiety Rating Scale ( HARS)
measure: Clinical antidepressant remission as defined by decline of HDRS-21 score over time
time frame: Day 20
description: Clinical antidepressant remission at the end of the treatment, defined as exit Hamilton Depression Rating Scale <10.
measure: Symptomatic improvement
time frame: day 20
description: Symptomatic improvement at the 4-week end point as measured with Quick Inventory of Depressive Symptomatology - Self Report (QIDS-SR)
measure: Symptomatic improvement
time frame: day 20
description: Symptomatic improvement at the 4-week end point as measured with Clinical Global Impression (CGI)
arm group label: single channel
arm group type: Active Comparator
arm group label: Two channels "Multiway stimulator coil®" (Brainsway Ltd.)
arm group type: Experimental
intervention type: Device
intervention name: single channel "Multiway Coil®"
description: During the single channel treatment trial period the patients will receive the following dose of rTMS: 10 Hz - left DLPFC ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks).
arm group label: single channel
intervention type: Device
intervention name: Two channels "Multiway stimulator coil®" (Brainsway Ltd.)
description: During the two channels treatment trial period the patients will receive the following dose of rTMS: 10 Hz- left DLPFC, 1Hz - right DLPFC together.
10 Hz protocol: ( 10 Hz, at 120% MT, 3 sec pulse train, 20 second inter-train interval, 55 trains, i.e. a total of 1650 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 33,000pulses in 4 weeks)
1 Hz protocol:
1 Hz, at 120% MT, 5 min pulse train, 1 min inter-train interval, 6 trains, i.e. a total of 1800 pulses per session, a total of 20 sessions in the study and a cumulative exposure (total number of pulses) of 36,000 pulses in 4 weeks).
arm group label: Two channels "Multiway stimulator coil®" (Brainsway Ltd.)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Yuval Bloch, Md, Phd
role: Principal Investigator
affiliation: Shalvata Mental Health Center
last name: Yuval Bloch, MD, Phd
phone: 097478644
email: yuvalbl@clalit.org.il
facility: 
contact: 
investigator: 
country: Israel
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major