<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/NCT02212366</url>
  </required_header>
  <id_info>
    <org_study_id>131/2013</org_study_id>
    <nct_id>NCT02212366</nct_id>
  </id_info>
  <brief_title>To Enhance Cognition in Late Life Depression Using Transcranial Direct Current Stimulation</brief_title>
  <official_title>Enhancing Cognition in Patients With Late-Life Depression: A Randomized Controlled Trial of Transcranial Direct Current Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ontario Ministry of Health and Long Term Care</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Late Life Depression (LLD) is a serious health problem which not only causes depressed mood&#xD;
      but also results in impairments in memory and attention. These impairments are likely to be&#xD;
      resistant to treatment, which increases the chances of developing dementia even after&#xD;
      successful treatment of mood.This study is a randomized controlled trial of transcranial&#xD;
      Direct Current Stimulation (tDCS) in people with LLD to enhance their cognition after&#xD;
      successful treatment of mood with established medications. tDCS is non invasive, relatively&#xD;
      inexpensive and portable, and has been found to be safe.This study also serves as a pilot&#xD;
      study to assess the effects of tDCS on cognition and neurophysiologic markers of cognition&#xD;
      among patients with LLD. Primary study hypothesis is that participants Participants&#xD;
      randomized to tDCS will perform better on a working memory task 2 weeks and 3 months&#xD;
      following the tDCS course.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      tDCS is a non-invasive brain stimulation method that utilizes low intensity electrical&#xD;
      current either to increase cortical excitability with an anodal electrode or to suppress&#xD;
      cortical excitability with a cathodal electrode. tDCS produces its effects through long&#xD;
      lasting changes in neuroplasticity: in animal studies, tDCS results in long-term potentiation&#xD;
      and brain-derived neurotrophic factor secretion; in human studies, tDCS results in&#xD;
      potentiation of neurophysiologic markers of neuroplasticity. Consistent with these&#xD;
      preclinical findings, tDCS to the temporoparietal cortex or left DLPFC improves memory in&#xD;
      patients with mild to moderate Alzheimer disease(AD). tDCS has also been tested among&#xD;
      patients with depression - including by our group - but mainly as a treatment for depressive&#xD;
      symptoms. In one recent large study one session of bilateral anodal tDCS was shown to enhance&#xD;
      working memory among midlife participants with major depression prior to receiving any&#xD;
      treatment. However, it is still not known (1) whether tDCS improves cognition beyond the&#xD;
      partial improvement that is associated with resolution of depressive symptoms; or (2) whether&#xD;
      it has a more fundamental and long lasting effect on cognition.&#xD;
&#xD;
      This trial will assess the acute and long-term effects of a 2-week course of daily (5&#xD;
      days/week) bilateral anodal tDCS of the DLPFC on cognition, and in particular working memory&#xD;
      among 36 patients with LLD. We will recruit and randomize participants who have already been&#xD;
      treated for LLD prior to consenting to the study and who still meet criteria for remission&#xD;
      while on antidepressant medications.&#xD;
&#xD;
      This trial will also be used as a platform to explore the effect of tDCS on neurophysiologic&#xD;
      measures of plasticity during working memory performance. Working memory is supported by&#xD;
      re-entrant circuits, some are local within the DLPFC and others are long-range connecting the&#xD;
      DLPFC to more posterior cortices. These networks result in high and low frequency neuronal&#xD;
      oscillations that can be captured by electroencephalography (EEG). Using novel&#xD;
      neurophysiologic analyses, our group and others have demonstrated that the modulation of&#xD;
      high-frequency (particularly gamma) oscillations by low-frequency (particularly theta)&#xD;
      oscillations - &quot;theta-gamma coupling&quot; - is a neurophysiologic marker of working memory. Thus,&#xD;
      we will explore the effect of tDCS on theta-gamma coupling.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>May 2014</start_date>
  <completion_date type="Actual">November 2017</completion_date>
  <primary_completion_date type="Actual">November 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups</measure>
    <time_frame>Two weeks following the TDCS course</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups</measure>
    <time_frame>Three months following the TDCS course</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups.</measure>
    <time_frame>Two weeks following the TDCS</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups.</measure>
    <time_frame>3 months following the TDCS</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Cognition</condition>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>Active TDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2-week course of daily (5 days/week) active bilateral anodal TDCS, duration 30 minute each session. Current 2 mA.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham TDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>2-week course of daily (5 days/week) Sham bilateral tDCS. Duration 30 minute each session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active TDCS</intervention_name>
    <description>Active Stimulation</description>
    <arm_group_label>Active TDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham TDCS</intervention_name>
    <description>Sham Stimulation</description>
    <arm_group_label>Sham TDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Women and men of any races or ethnicity&#xD;
&#xD;
          2. Age 60 and above&#xD;
&#xD;
          3. Major depressive disorder, single or recurrent per SCID DSM-IV criteria AND remission&#xD;
             from that episode as defined by DSM IV-TR criteria for remission.&#xD;
&#xD;
          4. Montgomery-Asberg Depression Rating Scale (MADRS) score less than 10.&#xD;
&#xD;
          5. Ability to speak English fluently enough to complete all research assessments.&#xD;
&#xD;
          6. Corrected visual ability to read newspaper headlines; hearing capacity to respond to a&#xD;
             raised conversational voice&#xD;
&#xD;
          7. Willingness and ability to provide consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. DSM IV TR criteria for any dementia&#xD;
&#xD;
          2. DSM IV TR criteria for life-time bipolar disorder, schizophrenia, schizoaffective&#xD;
             disorder, or other psychotic disorders&#xD;
&#xD;
          3. DSM IV TR criteria for any substance abuse or dependence within the past 6 months&#xD;
&#xD;
          4. Presence of psychotic features or any other symptoms that would make the participant&#xD;
             unable to participate in the study.&#xD;
&#xD;
          5. Any medical contra-indications to tDCS.&#xD;
&#xD;
          6. Electroconvulsive therapy in the last 6 months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>60 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Tarek K Rajji, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Center for Addiction and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M6J1H4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>January 2018</verification_date>
  <study_first_submitted>August 6, 2014</study_first_submitted>
  <study_first_submitted_qc>August 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 8, 2014</study_first_posted>
  <last_update_submitted>January 22, 2018</last_update_submitted>
  <last_update_submitted_qc>January 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Tarek Rajji</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>TDCS</keyword>
  <keyword>Depression</keyword>
  <keyword>Brain Stimulation</keyword>
  <keyword>Memory</keyword>
  <keyword>Cognition</keyword>
  <keyword>EEG</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/NCT02212366
org study id: 131/2013
nct id: NCT02212366
lead sponsor: 
collaborator: 
has dmc: No
Late Life Depression (LLD) is a serious health problem which not only causes depressed mood
      but also results in impairments in memory and attention. These impairments are likely to be
      resistant to treatment, which increases the chances of developing dementia even after
      successful treatment of mood.This study is a randomized controlled trial of transcranial
      Direct Current Stimulation (tDCS) in people with LLD to enhance their cognition after
      successful treatment of mood with established medications. tDCS is non invasive, relatively
      inexpensive and portable, and has been found to be safe.This study also serves as a pilot
      study to assess the effects of tDCS on cognition and neurophysiologic markers of cognition
      among patients with LLD. Primary study hypothesis is that participants Participants
      randomized to tDCS will perform better on a working memory task 2 weeks and 3 months
      following the tDCS course.
tDCS is a non-invasive brain stimulation method that utilizes low intensity electrical
      current either to increase cortical excitability with an anodal electrode or to suppress
      cortical excitability with a cathodal electrode. tDCS produces its effects through long
      lasting changes in neuroplasticity: in animal studies, tDCS results in long-term potentiation
      and brain-derived neurotrophic factor secretion; in human studies, tDCS results in
      potentiation of neurophysiologic markers of neuroplasticity. Consistent with these
      preclinical findings, tDCS to the temporoparietal cortex or left DLPFC improves memory in
      patients with mild to moderate Alzheimer disease(AD). tDCS has also been tested among
      patients with depression - including by our group - but mainly as a treatment for depressive
      symptoms. In one recent large study one session of bilateral anodal tDCS was shown to enhance
      working memory among midlife participants with major depression prior to receiving any
      treatment. However, it is still not known (1) whether tDCS improves cognition beyond the
      partial improvement that is associated with resolution of depressive symptoms; or (2) whether
      it has a more fundamental and long lasting effect on cognition.

      This trial will assess the acute and long-term effects of a 2-week course of daily (5
      days/week) bilateral anodal tDCS of the DLPFC on cognition, and in particular working memory
      among 36 patients with LLD. We will recruit and randomize participants who have already been
      treated for LLD prior to consenting to the study and who still meet criteria for remission
      while on antidepressant medications.

      This trial will also be used as a platform to explore the effect of tDCS on neurophysiologic
      measures of plasticity during working memory performance. Working memory is supported by
      re-entrant circuits, some are local within the DLPFC and others are long-range connecting the
      DLPFC to more posterior cortices. These networks result in high and low frequency neuronal
      oscillations that can be captured by electroencephalography (EEG). Using novel
      neurophysiologic analyses, our group and others have demonstrated that the modulation of
      high-frequency (particularly gamma) oscillations by low-frequency (particularly theta)
      oscillations - "theta-gamma coupling" - is a neurophysiologic marker of working memory. Thus,
      we will explore the effect of tDCS on theta-gamma coupling.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups
time frame: Two weeks following the TDCS course
measure: To compare performance on working memory task (N-Back) and neuropsychological battery between active and sham TDCS groups
time frame: Three months following the TDCS course
measure: To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups.
time frame: Two weeks following the TDCS
measure: To compare theta-gamma coupling as measured by electroencephalography between active and sham TDCS groups.
time frame: 3 months following the TDCS
arm group label: Active TDCS
arm group type: Experimental
description: 2-week course of daily (5 days/week) active bilateral anodal TDCS, duration 30 minute each session. Current 2 mA.
arm group label: Sham TDCS
arm group type: Sham Comparator
description: 2-week course of daily (5 days/week) Sham bilateral tDCS. Duration 30 minute each session.
intervention type: Device
intervention name: Active TDCS
description: Active Stimulation
arm group label: Active TDCS
intervention type: Device
intervention name: Sham TDCS
description: Sham Stimulation
arm group label: Sham TDCS
criteria: 
gender: All
minimum age: 60 Years
maximum age: N/A
healthy volunteers: No
last name: Tarek K Rajji, MD
role: Principal Investigator
affiliation: Center for Addiction and Mental Health
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Tarek Rajji
investigator title: Principal Investigator
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: No