<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/NCT01677078</url>
  </required_header>
  <id_info>
    <org_study_id>2011-A01272-39</org_study_id>
    <nct_id>NCT01677078</nct_id>
  </id_info>
  <brief_title>Coupling Repetitive Transcranial Magnetic Stimulation With a Neuronavigation System in Treatment Resistant Depression</brief_title>
  <acronym>TMS</acronym>
  <official_title>Assessment of the Neuronavigation System Coupled With Repetitive Transcranial Magnetic Stimulation. A Randomized Double Blind Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rennes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rennes University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was&#xD;
      shown to be effective in the treatment of major depression.&#xD;
&#xD;
      The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the&#xD;
      standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference.&#xD;
      Nevertheless, it has been criticized due to poor targeting accuracies attributed to&#xD;
      inter-subject variability.&#xD;
&#xD;
      Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.&#xD;
&#xD;
      Preliminary findings suggest that a more reproductible and accurate method, based upon a&#xD;
      neuronavigation system could allow for a better efficacy. This finding has to be replicated&#xD;
      with sound methodology.&#xD;
&#xD;
      Investigator's objective is to compare efficacy on mood of coil positioning based upon a&#xD;
      neuronavigation device versus coil positioning based upon the standard method.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Background :&#xD;
&#xD;
      Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive&#xD;
      disorder.&#xD;
&#xD;
      rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue&#xD;
      cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly&#xD;
      changing magnetic field; this can modify activity in specific or general parts of the brain.&#xD;
&#xD;
      Meta-analyses have stated that rTMS appeared to be effective in the treatment of major&#xD;
      depression despite any limits concerning sample sizes and methodological concerns.&#xD;
&#xD;
      Studies have shown that this technique potentiates antidepressants treatment in combination&#xD;
      therapy.&#xD;
&#xD;
      It has received FDA approval for the management of major depressive disorder. Stimulation&#xD;
      parameters are numerous (frequency, intensity, number of pulses) and their effects are&#xD;
      increasingly better understood in order to predict a better balance between efficacy and&#xD;
      tolerability.&#xD;
&#xD;
      The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic&#xD;
      stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic&#xD;
      stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting&#xD;
      accuracies attributed to inter-subject variability.&#xD;
&#xD;
      Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary&#xD;
      findings suggest that a more reproductible and accurate method, based upon a neuronavigation&#xD;
      system could allow for a better efficacy. This finding has to be replicated with sound&#xD;
      methodology.&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To compare efficacy on mood of coil positioning based upon a neuronavigation device versus&#xD;
      coil positioning based upon the standard method.&#xD;
&#xD;
      Investigators hypothesized that an accurate localization and stimulation of DLPFC using&#xD;
      neuronavigation would be more effective than the less accurate standard method.&#xD;
&#xD;
      A secondary objective is to compare the efficacy on patient's self perception, on psychomotor&#xD;
      symptoms and the tolerability of the two methods.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 21, 2013</start_date>
  <completion_date type="Actual">March 25, 2017</completion_date>
  <primary_completion_date type="Actual">March 25, 2017</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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response</measure>
    <time_frame>Day 44</time_frame>
    <description>Response defined as at least 50% reduction in the MADRS score.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Response</measure>
    <time_frame>Day 14</time_frame>
    <description>Response is defined as at least 50% reduction in the MADRS score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Remission</measure>
    <time_frame>Day 14 Day 44</time_frame>
    <description>Remission is defined as a MADRS score ≤ 8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MADRS</measure>
    <time_frame>Day 0, day 14 and day 44</time_frame>
    <description>Description: It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDI</measure>
    <time_frame>Day 0 Day 14 Day 14</time_frame>
    <description>It is a multiple-choice self-report inventory and one of the most widely used instruments for measuring the severity of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ERD</measure>
    <time_frame>Day 0 Day 14 day 44</time_frame>
    <description>It is a 14-item questionnaire which psychiatrists use to measure the intensity of motor retardation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">107</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>Neuronavigation system</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 sessions of rTMS coupled with a neuronavigation system&#xD;
Description of 1 session of the rTMS protocol :&#xD;
Frequency: 20Hz&#xD;
Intensity: 110% of motor threshold&#xD;
80 train of 2 seconds duration&#xD;
10 seconds between two trains&#xD;
3200 pulses&#xD;
Devices :&#xD;
rTMS: System Mag Pro (Magventure, Denmark)&#xD;
Neuronavigation system: Syneika One (Syneika, France)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Standard localisation method</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>10 sessions of rTMS with manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')&#xD;
Description of 1 session of the rTMS protocol :&#xD;
Frequency: 20Hz&#xD;
Intensity: 110% of motor threshold&#xD;
80 train of 2 seconds duration&#xD;
10 seconds between two trains&#xD;
3200 pulses&#xD;
Devices :&#xD;
- rTMS: System Mag Pro (Magventure, Denmark)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neuronavigation system</intervention_name>
    <description>Neuronavigation</description>
    <arm_group_label>Neuronavigation system</arm_group_label>
    <other_name>Syneika One (Syneika, France)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Standard localisation method</intervention_name>
    <description>Manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')</description>
    <arm_group_label>Standard localisation method</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients giving their consent;&#xD;
&#xD;
          -  Right handed;&#xD;
&#xD;
          -  Age &gt; 18 and &lt; 65;&#xD;
&#xD;
          -  With a DSM-IV diagnosis of MDD, single episode or recurrent;&#xD;
&#xD;
          -  With an antidepressant treatment unchanged in the 3 last weeks;&#xD;
&#xD;
          -  With an MADRS score ≥ 21;&#xD;
&#xD;
          -  Benzodiazepine treatments have to be avoided;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Major depressive episode with psychotic characteristics;&#xD;
&#xD;
          -  A lifetime of the following axis 1 diagnoses: schizophrenia or substance use disorder&#xD;
             (alcohol or other substance);&#xD;
&#xD;
          -  Stade 5 of Thase and Rush classification ;&#xD;
&#xD;
          -  Involuntary hospitalizations;&#xD;
&#xD;
          -  Patients under guardianship;&#xD;
&#xD;
          -  Outpatients in case of an increased risk of suicide as assessed by a MADRS item 10 &gt;&#xD;
             3;&#xD;
&#xD;
          -  Contraindication for MRI or rTMS: a personal history of a seizure disorder, presence&#xD;
             of neurologic or neurosurgical disorder, presence of ferromagnetic material (including&#xD;
             intraocular) or metallic medical devices (pacemakers);&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruno Millet, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Rennes</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Jean Michel Reymann, PhD</last_name>
    <role>Study Chair</role>
    <affiliation>CHU Rennes</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Santé Mentale Angevin CESAME</name>
      <address>
        <city>Angers</city>
        <zip>49130</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Brest</name>
      <address>
        <city>Brest</city>
        <zip>29200</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Etablissement Public de Santé Mentale</name>
      <address>
        <city>Quimperlé</city>
        <zip>29300</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHGR</name>
      <address>
        <city>Rennes</city>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>EPSM Morbihan</name>
      <address>
        <city>St Avé</city>
        <zip>56890</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>August 2018</verification_date>
  <study_first_submitted>August 29, 2012</study_first_submitted>
  <study_first_submitted_qc>August 30, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 31, 2012</study_first_posted>
  <last_update_submitted>August 28, 2018</last_update_submitted>
  <last_update_submitted_qc>August 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Major depressive disorder</keyword>
  <keyword>rTMS</keyword>
  <keyword>Neuronavigation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</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/NCT01677078
org study id: 2011-A01272-39
nct id: NCT01677078
lead sponsor: 
has dmc: No
Repetitive Transcranial Magnetic Stimulation (rTMS) is a non invasive technique which was
      shown to be effective in the treatment of major depression.

      The dorsolateral prefrontal cortex (DLPFC) is the anatomic target in rTMS studies and the
      standard (manual) '5-cm method' for positioning the coil over DLPFC is the reference.
      Nevertheless, it has been criticized due to poor targeting accuracies attributed to
      inter-subject variability.

      Such an inaccuracy could have any therapeutic consequences as a decrease in rTMS efficacy.

      Preliminary findings suggest that a more reproductible and accurate method, based upon a
      neuronavigation system could allow for a better efficacy. This finding has to be replicated
      with sound methodology.

      Investigator's objective is to compare efficacy on mood of coil positioning based upon a
      neuronavigation device versus coil positioning based upon the standard method.
Background :

      Repetitive Transcranial Magnetic Stimulation (rTMS) is a new tool for major depressive
      disorder.

      rTMS is a non invasive technique allowing for a localized stimulation of cerebral tissue
      cortex. rTMS uses electromagnetic induction to induce weak electric currents using a rapidly
      changing magnetic field; this can modify activity in specific or general parts of the brain.

      Meta-analyses have stated that rTMS appeared to be effective in the treatment of major
      depression despite any limits concerning sample sizes and methodological concerns.

      Studies have shown that this technique potentiates antidepressants treatment in combination
      therapy.

      It has received FDA approval for the management of major depressive disorder. Stimulation
      parameters are numerous (frequency, intensity, number of pulses) and their effects are
      increasingly better understood in order to predict a better balance between efficacy and
      tolerability.

      The dorsolateral prefrontal cortex (DLPFC) is the target in repetitive transcranial magnetic
      stimulation and the standard (manual) '5-cm method' for positioning the transcranial magnetic
      stimulation coil over DLPFC is the reference. It has been criticized due to poor targeting
      accuracies attributed to inter-subject variability.

      Such an inaccuracy could have consequences as a decrease in rTMS efficacy. Any preliminary
      findings suggest that a more reproductible and accurate method, based upon a neuronavigation
      system could allow for a better efficacy. This finding has to be replicated with sound
      methodology.

      Objectives:

      To compare efficacy on mood of coil positioning based upon a neuronavigation device versus
      coil positioning based upon the standard method.

      Investigators hypothesized that an accurate localization and stimulation of DLPFC using
      neuronavigation would be more effective than the less accurate standard method.

      A secondary objective is to compare the efficacy on patient's self perception, on psychomotor
      symptoms and the tolerability of the two methods.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Response
time frame: Day 44
description: Response defined as at least 50% reduction in the MADRS score.
measure: Response
time frame: Day 14
description: Response is defined as at least 50% reduction in the MADRS score.
measure: Remission
time frame: Day 14 Day 44
description: Remission is defined as a MADRS score ≤ 8.
measure: MADRS
time frame: Day 0, day 14 and day 44
description: Description: It is a ten-item diagnostic questionnaire which psychiatrists use to measure the severity of depressive episodes in patients with mood disorders.
measure: BDI
time frame: Day 0 Day 14 Day 14
description: It is a multiple-choice self-report inventory and one of the most widely used instruments for measuring the severity of depression.
measure: ERD
time frame: Day 0 Day 14 day 44
description: It is a 14-item questionnaire which psychiatrists use to measure the intensity of motor retardation.
arm group label: Neuronavigation system
arm group type: Experimental
description: 10 sessions of rTMS coupled with a neuronavigation system
Description of 1 session of the rTMS protocol :
Frequency: 20Hz
Intensity: 110% of motor threshold
80 train of 2 seconds duration
10 seconds between two trains
3200 pulses
Devices :
rTMS: System Mag Pro (Magventure, Denmark)
Neuronavigation system: Syneika One (Syneika, France)
arm group label: Standard localisation method
arm group type: Sham Comparator
description: 10 sessions of rTMS with manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')
Description of 1 session of the rTMS protocol :
Frequency: 20Hz
Intensity: 110% of motor threshold
80 train of 2 seconds duration
10 seconds between two trains
3200 pulses
Devices :
- rTMS: System Mag Pro (Magventure, Denmark)
intervention type: Device
intervention name: Neuronavigation system
description: Neuronavigation
arm group label: Neuronavigation system
other name: Syneika One (Syneika, France)
intervention type: Device
intervention name: Standard localisation method
description: Manual localisation of the DLPFC using the standard localisation method (i.e. the '5-cm method')
arm group label: Standard localisation method
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Bruno Millet, MD PhD
role: Principal Investigator
affiliation: CHU Rennes
last name: Jean Michel Reymann, PhD
role: Study Chair
affiliation: CHU Rennes
facility: 
facility: 
facility: 
facility: 
facility: 
country: France
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant