<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/NCT03279913</url>
  </required_header>
  <id_info>
    <org_study_id>35RC16_8939_NEUROFEEDSTIM</org_study_id>
    <secondary_id>2017-A00809-44</secondary_id>
    <secondary_id>17/051-1</secondary_id>
    <nct_id>NCT03279913</nct_id>
  </id_info>
  <brief_title>NEUROFEEDSTIM : Therapeutic Use of Neurofeedback in Depression in Association With TMS</brief_title>
  <acronym>NEUROFEEDSTIM</acronym>
  <official_title>NEUROFEEDSTIM : Therapeutic Use of Neurofeedback in Depression in Association With TMS</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>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Neurofeedback is an increasingly researched technique for the treatment of many psychological&#xD;
      disorders, such as attention deficit / hyperactivity disorder (AD / HD), depression, or&#xD;
      substance abuse. This technique would allow patients to regulate their cortical&#xD;
      electroencephalographic activity while receiving a visual or auditory feedback on the&#xD;
      cortical electroencephalographic activity. Changes in the electroencephalogram (EEG) would&#xD;
      thus be correlated with changes in cortical activity and thus with symptoms.&#xD;
&#xD;
      On the electroencephalographic plane, the depression appears associated with relatively more&#xD;
      alpha activity (in &quot;resting state&quot;, 8-13 Hz) in left than in right frontal cortex. This&#xD;
      difference in alpha activity between frontal regions is known as alpha asymmetry in&#xD;
      depression. As a reminder, increased alpha activity indicates a decrease in cortical&#xD;
      activation. This alpha asymmetry appears to be associated with a decrease in sensitivity to&#xD;
      reward.&#xD;
&#xD;
      It is on these bases that the modification of the alpha asymmetry has become one of the most&#xD;
      frequent objectives of the studies on the use of neurofeedback in depression.&#xD;
&#xD;
      Transcranial magnetic stimulation (TMS) also offers a non-invasive and painless method of&#xD;
      effective cerebral stimulation in psychiatric disorders and especially depression. It&#xD;
      received a favorable opinion from the Food &amp; Drug Administration (FDA) in the United States&#xD;
      for the treatment of this pathology. This treatment is still under evaluation in France. The&#xD;
      results are promising but improvements must be done to increase its effectiveness.&#xD;
&#xD;
      TMS offers stimulation of brain tissue in a localized and non-invasive manner. The principle&#xD;
      consists of a brief electric current passing through a coil which generates a transient&#xD;
      magnetic field inducing an electric field through conductive fabrics. TMS modifies neuronal&#xD;
      activity in target superficial brain structures, but also modulates neuronal circuit&#xD;
      activity.&#xD;
&#xD;
      In recent years, the concept of &quot;state dependency TMS&quot; has been developed. It suggests that&#xD;
      the activation state of neuronal circuits before and after stimulation alters the effect of&#xD;
      stimulation. Thus, the efficacy of TMS could be amplified in depression by taking into&#xD;
      account the cerebral activity during the stimulation sessions, in particular on the&#xD;
      electroencephalographic plane.&#xD;
&#xD;
      However, TMS may also help patients increase their EEG response during Neurofeedback&#xD;
      sessions.&#xD;
&#xD;
      The combination of stimulation techniques and brain-machine interfaces such as neurofeedback&#xD;
      is still little studied at present.&#xD;
&#xD;
      A study on the combined use of TMS and Neurofeedback by EEG in depression would therefore be&#xD;
      an innovative approach and in line with the latest data from the literature.&#xD;
&#xD;
      Design : Prospective, monocentric, non-randomized, non-comparative, unblinded study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary objective : To demonstrate a decrease in the intensity of depressive symptomatology&#xD;
      following EEG-neurofeedback training in association with TMS and see if there is a&#xD;
      correlation with a change in frontal asymmetry.&#xD;
&#xD;
      Secondary objective : To demonstrate a cognitive improvement in patients with respect to&#xD;
      motivation and control of thoughts, as well as perceived health, self-esteem and anxiety&#xD;
      following EEG-neurofeedback training in association with TMS and to see if there is a&#xD;
      correlation between the change in scores on psychometric scales with a change in frontal&#xD;
      asymmetry.&#xD;
&#xD;
      The expected outcomes of this study are:&#xD;
&#xD;
        -  Better characterization of the pathophysiological processes involved in depressive&#xD;
           disorder;&#xD;
&#xD;
        -  An evaluation of the effectiveness of EEG-Neurofeedback training in recurrent depressive&#xD;
           disorder in association with TMS, both emotionally and cognitively;&#xD;
&#xD;
        -  The development of innovative technologies in the field of brain-machine interfaces and&#xD;
           optimization of procedures.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 18, 2017</start_date>
  <completion_date type="Actual">September 7, 2019</completion_date>
  <primary_completion_date type="Actual">September 7, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>MADRS score</measure>
    <time_frame>Baseline and day 12</time_frame>
    <description>Total score at the MADRS (Montgomery and Asberg Depression Scale) scale: difference between day 1 and day 12.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>MADRS score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the MADRS score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BDI score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the BDI score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HAM-A score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the HAM-A score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>TCAQ score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the TCAQ score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BIS-BAS system score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the BIS-BAS system score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>SES score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the SES score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MHLCS score</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the MHLCS score between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuropsychological test</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the neuropsychological performance between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frontal asymmetry alpha measurement.</measure>
    <time_frame>Day 1, day 12 and month 1</time_frame>
    <description>Difference at the frontal asymmetry alpha between day 1, day 12 and month 1</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>EEG-neurofeedback training in association with TMS.</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>EEG-neurofeedback training in association with TMS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>EEG-neurofeedback training in association with TMS.</intervention_name>
    <description>EEG-neurofeedback training in association with TMS.</description>
    <arm_group_label>EEG-neurofeedback training in association with TMS.</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patient with a major depressive episode (DSM IV-TR 296) with an indication of TMS&#xD;
             (whether or not they have previously benefited from TMS);&#xD;
&#xD;
          -  Aged 18 and over;&#xD;
&#xD;
          -  With a score greater than or equal to 15 at the MADRS;&#xD;
&#xD;
          -  Under stable and unchanged pharmacological treatment for at least one month;&#xD;
&#xD;
          -  Having signed a free and informed consent to participate in the study.&#xD;
&#xD;
        Non inclusion Criteria:&#xD;
&#xD;
          -  Other psychiatric disorder of axis 1 of DSM IV-TR (schizophrenia, substance abuse /&#xD;
             dependence, ...);&#xD;
&#xD;
          -  Neurological or dementia history according to DSM criteria;&#xD;
&#xD;
          -  Pregnant or nursing women;&#xD;
&#xD;
          -  Major persons subject to legal protection (safeguard of justice, curators,&#xD;
             guardianship);&#xD;
&#xD;
          -  Participation in another research involving the human interventionist or at risk and&#xD;
             minimal constraints&#xD;
&#xD;
          -  Confined hospitalized patients (SDT, SDRE).&#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_official>
    <last_name>Dominique Drapier, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre Hospitalier Guillaume Regnier</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre Hospitalier Guillaume Régnier</name>
      <address>
        <city>Rennes</city>
        <state>Britanny</state>
        <zip>35000</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>November 2019</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>November 5, 2019</last_update_submitted>
  <last_update_submitted_qc>November 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Depression, neurofeedback, TMS</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>
  </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/NCT03279913
org study id: 35RC16_8939_NEUROFEEDSTIM
secondary id: 2017-A00809-44
secondary id: 17/051-1
nct id: NCT03279913
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Neurofeedback is an increasingly researched technique for the treatment of many psychological
      disorders, such as attention deficit / hyperactivity disorder (AD / HD), depression, or
      substance abuse. This technique would allow patients to regulate their cortical
      electroencephalographic activity while receiving a visual or auditory feedback on the
      cortical electroencephalographic activity. Changes in the electroencephalogram (EEG) would
      thus be correlated with changes in cortical activity and thus with symptoms.

      On the electroencephalographic plane, the depression appears associated with relatively more
      alpha activity (in "resting state", 8-13 Hz) in left than in right frontal cortex. This
      difference in alpha activity between frontal regions is known as alpha asymmetry in
      depression. As a reminder, increased alpha activity indicates a decrease in cortical
      activation. This alpha asymmetry appears to be associated with a decrease in sensitivity to
      reward.

      It is on these bases that the modification of the alpha asymmetry has become one of the most
      frequent objectives of the studies on the use of neurofeedback in depression.

      Transcranial magnetic stimulation (TMS) also offers a non-invasive and painless method of
      effective cerebral stimulation in psychiatric disorders and especially depression. It
      received a favorable opinion from the Food & Drug Administration (FDA) in the United States
      for the treatment of this pathology. This treatment is still under evaluation in France. The
      results are promising but improvements must be done to increase its effectiveness.

      TMS offers stimulation of brain tissue in a localized and non-invasive manner. The principle
      consists of a brief electric current passing through a coil which generates a transient
      magnetic field inducing an electric field through conductive fabrics. TMS modifies neuronal
      activity in target superficial brain structures, but also modulates neuronal circuit
      activity.

      In recent years, the concept of "state dependency TMS" has been developed. It suggests that
      the activation state of neuronal circuits before and after stimulation alters the effect of
      stimulation. Thus, the efficacy of TMS could be amplified in depression by taking into
      account the cerebral activity during the stimulation sessions, in particular on the
      electroencephalographic plane.

      However, TMS may also help patients increase their EEG response during Neurofeedback
      sessions.

      The combination of stimulation techniques and brain-machine interfaces such as neurofeedback
      is still little studied at present.

      A study on the combined use of TMS and Neurofeedback by EEG in depression would therefore be
      an innovative approach and in line with the latest data from the literature.

      Design : Prospective, monocentric, non-randomized, non-comparative, unblinded study.
Primary objective : To demonstrate a decrease in the intensity of depressive symptomatology
      following EEG-neurofeedback training in association with TMS and see if there is a
      correlation with a change in frontal asymmetry.

      Secondary objective : To demonstrate a cognitive improvement in patients with respect to
      motivation and control of thoughts, as well as perceived health, self-esteem and anxiety
      following EEG-neurofeedback training in association with TMS and to see if there is a
      correlation between the change in scores on psychometric scales with a change in frontal
      asymmetry.

      The expected outcomes of this study are:

        -  Better characterization of the pathophysiological processes involved in depressive
           disorder;

        -  An evaluation of the effectiveness of EEG-Neurofeedback training in recurrent depressive
           disorder in association with TMS, both emotionally and cognitively;

        -  The development of innovative technologies in the field of brain-machine interfaces and
           optimization of procedures.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: MADRS score
time frame: Baseline and day 12
description: Total score at the MADRS (Montgomery and Asberg Depression Scale) scale: difference between day 1 and day 12.
measure: MADRS score
time frame: Day 1, day 12 and month 1
description: Difference at the MADRS score between day 1, day 12 and month 1
measure: BDI score
time frame: Day 1, day 12 and month 1
description: Difference at the BDI score between day 1, day 12 and month 1
measure: HAM-A score
time frame: Day 1, day 12 and month 1
description: Difference at the HAM-A score between day 1, day 12 and month 1
measure: TCAQ score
time frame: Day 1, day 12 and month 1
description: Difference at the TCAQ score between day 1, day 12 and month 1
measure: BIS-BAS system score
time frame: Day 1, day 12 and month 1
description: Difference at the BIS-BAS system score between day 1, day 12 and month 1
measure: SES score
time frame: Day 1, day 12 and month 1
description: Difference at the SES score between day 1, day 12 and month 1
measure: MHLCS score
time frame: Day 1, day 12 and month 1
description: Difference at the MHLCS score between day 1, day 12 and month 1
measure: Neuropsychological test
time frame: Day 1, day 12 and month 1
description: Difference at the neuropsychological performance between day 1, day 12 and month 1
measure: Frontal asymmetry alpha measurement.
time frame: Day 1, day 12 and month 1
description: Difference at the frontal asymmetry alpha between day 1, day 12 and month 1
arm group label: EEG-neurofeedback training in association with TMS.
arm group type: Experimental
description: EEG-neurofeedback training in association with TMS.
intervention type: Device
intervention name: EEG-neurofeedback training in association with TMS.
description: EEG-neurofeedback training in association with TMS.
arm group label: EEG-neurofeedback training in association with TMS.
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dominique Drapier, MD
role: Principal Investigator
affiliation: Centre Hospitalier Guillaume Regnier
facility: 
country: France
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No