<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/NCT04507243</url>
  </required_header>
  <id_info>
    <org_study_id>20-001544</org_study_id>
    <secondary_id>R33MH110526</secondary_id>
    <nct_id>NCT04507243</nct_id>
  </id_info>
  <brief_title>Transcranial Direct Current Stimulation (tDCS) Therapy in Major Depression</brief_title>
  <official_title>Imaging-guided tDCS Therapy in Major Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</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>
      Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation&#xD;
      technique of minimal risk that has been used as an experimental procedure for reducing&#xD;
      depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal&#xD;
      brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD),&#xD;
      the extent of antidepressant response often differs. Methods that map current flow directly&#xD;
      in the brain while a person is receiving tDCS and that determine how functional neuroimaging&#xD;
      signal changes after a series of tDCS sessions may help us understand how tDCS works, how it&#xD;
      can be optimized, and if it can be used as an effective antidepressant. Investigators will&#xD;
      address these questions in a two-part randomized double blind exploratory clinical trial. For&#xD;
      this part of the study, investigators will determine relationships between target engagement&#xD;
      and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion&#xD;
      negativity bias, and whether imaging markers at baseline predict changes in antidepressant&#xD;
      response.&#xD;
&#xD;
      One hundred people with depression (50 in each group) will be randomized to receive either&#xD;
      HD-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on&#xD;
      consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of&#xD;
      active or sham HD-tDCS in the MRI scanner, which will allow investigators to map tDCS&#xD;
      currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment&#xD;
      using completely non-invasive methods. At the first and last session and mid-way through the&#xD;
      trial, participants will also complete a series of clinical ratings and neurocognitive tests.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique,&#xD;
      applied to the left dorsolateral prefrontal cortex (DLPFC) can reduce depressive symptoms and&#xD;
      improve cognitive control in major depressive disorder (MDD). Such findings suggest&#xD;
      modulation of top down prefrontal-limbic circuits, which are functionally distinct from&#xD;
      ventro-limbic networks and include reciprocally connected DLPFC and dorsomedial anterior&#xD;
      cingulate cortex (dACC). However, substantial variation in tDCS response is observed in MDD.&#xD;
      This may be due to imprecise stimulation protocols and suboptimal engagement of the neural&#xD;
      circuits mediating antidepressant response. Methods that optimize electrode placement and&#xD;
      account for individual variation in anatomy and that map current flow directly in the brain&#xD;
      may inform the mechanisms and potential clinical utility of tDCS. A new tDCS technique, high&#xD;
      definition (HD) tDCS, offers more focal stimulation than conventional tDCS (C-tDCS). The&#xD;
      degree to which C-tDCS or HD-tDCS engage dorsal prefrontal-limbic neural circuits is unknown,&#xD;
      yet is vital for understanding, confirming and subsequently improving possible therapeutic&#xD;
      effects. Innovative MRI techniques that are able to map tDCS currents in vivo and that track&#xD;
      changes in regional cerebral blood flow occurring with tDCS over time can provide direct&#xD;
      evidence of neural effects. Based on a) theoretical modeling of tDCS current flow, b) studies&#xD;
      showing hypo-metabolism, decreased CBF or activity in dorsal prefrontal-limbic networks, c)&#xD;
      modulation of these regions with treatment, and, c) our prior results showing significant&#xD;
      relationships in between change in dACC rCBF and clinical response to electroconvulsive&#xD;
      therapy (ECT), an established brain stimulation treatment, we will test for the tDCS&#xD;
      engagement and modulation of the DLPFC and dACC using tDCS current mapping performed in vivo&#xD;
      and perfusion MRI. MRI-guided neuronavigation will be used to optimize and standardize&#xD;
      electrode placement for DLPFC stimulation.&#xD;
&#xD;
      In this trial, using HD-tDCS that optimal target engagement of DLPFC and larger rCBF changes&#xD;
      in the DLPFC and dACC compared to C-tDCS in the first part of the trial, we will define&#xD;
      relationships between target engagement and change in mood and behavior. Patients with&#xD;
      moderate to severe MDD (N=100, n=50 in each group) will be randomized to Active or Sham left&#xD;
      anodal DLPFC HD-tDCS. Patients will complete MRI scans including tDCS current mapping and&#xD;
      pCASL as well as two functional imaging tasks probing cognitive control and emotion&#xD;
      negativity bias, recruiting prefrontal-limbic circuitry, before and after completing a 12-day&#xD;
      trial of 20-minute tDCS sessions.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 1, 2020</start_date>
  <completion_date type="Anticipated">April 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">April 1, 2023</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>
    <intervention_model_description>Active and Sham controlled</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Double blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Measured joint longitudinal change in rCBF and mood scores over the tDCS trial</measure>
    <time_frame>3 weeks</time_frame>
    <description>Correlation between percent change in rCBF after the tDCS trial and percent change in depressive symptoms for active versus sham tDCS conditions</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Measured joint longitudinal change in regional brain activation and mood scores over the tDCS trial</measure>
    <time_frame>3 weeks</time_frame>
    <description>Correlation between percent change in regional brain activation for tasks probing cognitive control and emotion and percent change depressive symptoms for active versus sham tDCS conditions</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measured magnetic fields and rCBF at baseline and change in mood scores over the tDCS trial</measure>
    <time_frame>3 weeks</time_frame>
    <description>Correlation between variations in magnetic fields and rCBF at baseline and clinical outcomes at the end of the tDCS treatment trial</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Active - HD tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this arm will receive 12 sessions of high definition tDCS (HD-tDCS) stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham - HD tDCS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Participants randomized to this arm will receive 12 sessions of sham HD tDCS stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active - HD tDCS</intervention_name>
    <description>Non-invasive neuromodulation using HD electrodes placed on the scalp to deliver a constant, low current at 2 mA.</description>
    <arm_group_label>Active - HD tDCS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham - HD tDCS</intervention_name>
    <description>Sham neuromodulation using HD electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec.</description>
    <arm_group_label>Sham - HD tDCS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Capacity to provide informed consent;&#xD;
&#xD;
          -  Meet DSM-5 criteria for a moderate-to-severe MDE, with Hamilton Rating Scale for&#xD;
             Depression (HAMD) score of ≥14 and &lt;24;&#xD;
&#xD;
          -  Treatment naïve or on a stable standard antidepressant regimen (including selective&#xD;
             serotonin reuptake inhibitors (SSRIs), serotonin-noradrenaline reuptake inhibitors&#xD;
             (SNRIs), monoamine oxidase inhibitors (MOAIs) or tricyclic's (TCAs)) with no change in&#xD;
             treatment 6-weeks prior to and during the tDCS intervention;&#xD;
&#xD;
          -  Live within traveling distance to the University of California, Los Angeles (UCLA);&#xD;
&#xD;
          -  Must refrain from making drastic hair-style changes throughout duration of study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Non-English speaking;&#xD;
&#xD;
          -  Schizophrenia Axis I disorder;&#xD;
&#xD;
          -  Primary anxiety disorder;&#xD;
&#xD;
          -  Bipolar I disorder and psychotic disorders;&#xD;
&#xD;
          -  Any neurological condition or major illness, including seizure disorder;&#xD;
&#xD;
          -  Diagnosis of dementia of any type;&#xD;
&#xD;
          -  Co-morbid substance abuse in the last three months;&#xD;
&#xD;
          -  Contraindications to MR scanning (including pregnancy);&#xD;
&#xD;
          -  Contraindications to tDCS (e.g., skin disease or treatment causing irritation);&#xD;
&#xD;
          -  Treatment-resistant depression, with a history of a major depressive episode lasting &gt;&#xD;
             2 years or failure to 2 or more antidepressant trials in the current episode;&#xD;
&#xD;
          -  Any neuromodulation therapy (e.g., ECT, rTMS, DBS, VNS, or tDCS) within the last 3&#xD;
             months;&#xD;
&#xD;
          -  Active suicidality;&#xD;
&#xD;
          -  Current or past (within the last 1-month) use of anticonvulsants, lithium,&#xD;
             psychostimulants, or dexamphetamine;&#xD;
&#xD;
          -  Current use of decongestants or other medication previously shown to interfere with&#xD;
             cortical excitability;&#xD;
&#xD;
          -  Currently receiving any form of Cognitive Behavioral Therapy, Dialectical Behavioral&#xD;
             Therapy, or Acceptance and Commitment Therapy&#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>Katherine L Narr, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Suzanne Kozikowski, MS</last_name>
    <phone>(424) 402-9051</phone>
    <email>DGCNeurostimStudy@mednet.ucla.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of California, Los Angeles (UCLA)</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suzanne Kozikowski, MS</last_name>
      <phone>424-402-9051</phone>
      <email>DGCNeurostimStudy@mednet.ucla.edu</email>
    </contact>
    <investigator>
      <last_name>Katherine L Narr, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 4, 2020</study_first_submitted>
  <study_first_submitted_qc>August 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 11, 2020</study_first_posted>
  <last_update_submitted>May 16, 2022</last_update_submitted>
  <last_update_submitted_qc>May 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, Los Angeles</investigator_affiliation>
    <investigator_full_name>Katherine Narr</investigator_full_name>
    <investigator_title>Professor, Department of Neurology, Psychiatry and Biobehavioral Sciences</investigator_title>
  </responsible_party>
  <keyword>Transcranial direct current stimulation</keyword>
  <keyword>MRI</keyword>
  <keyword>Major Depression</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, Major</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/NCT04507243
org study id: 20-001544
secondary id: R33MH110526
nct id: NCT04507243
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Noninvasive transcranial direct current stimulation (tDCS) is a low-intensity neuromodulation
      technique of minimal risk that has been used as an experimental procedure for reducing
      depressive symptoms and symptoms of other brain disorders. Though tDCS applied to prefrontal
      brain areas is shown to reduce symptoms in some people with major depressive disorder (MDD),
      the extent of antidepressant response often differs. Methods that map current flow directly
      in the brain while a person is receiving tDCS and that determine how functional neuroimaging
      signal changes after a series of tDCS sessions may help us understand how tDCS works, how it
      can be optimized, and if it can be used as an effective antidepressant. Investigators will
      address these questions in a two-part randomized double blind exploratory clinical trial. For
      this part of the study, investigators will determine relationships between target engagement
      and clinical outcomes (mood) and functional sub-constructs of cognitive control and emotion
      negativity bias, and whether imaging markers at baseline predict changes in antidepressant
      response.

      One hundred people with depression (50 in each group) will be randomized to receive either
      HD-tDCS or sham-tDCS for a total of 12 sessions each lasting 20 minutes occurring on
      consecutive weekdays. At the first and last session, subjects will receive 20-30 minutes of
      active or sham HD-tDCS in the MRI scanner, which will allow investigators to map tDCS
      currents, and track changes in regional cerebral blood flow (rCBF) pre-to- post treatment
      using completely non-invasive methods. At the first and last session and mid-way through the
      trial, participants will also complete a series of clinical ratings and neurocognitive tests.
Transcranial direct current stimulation (tDCS), a noninvasive neuromodulation technique,
      applied to the left dorsolateral prefrontal cortex (DLPFC) can reduce depressive symptoms and
      improve cognitive control in major depressive disorder (MDD). Such findings suggest
      modulation of top down prefrontal-limbic circuits, which are functionally distinct from
      ventro-limbic networks and include reciprocally connected DLPFC and dorsomedial anterior
      cingulate cortex (dACC). However, substantial variation in tDCS response is observed in MDD.
      This may be due to imprecise stimulation protocols and suboptimal engagement of the neural
      circuits mediating antidepressant response. Methods that optimize electrode placement and
      account for individual variation in anatomy and that map current flow directly in the brain
      may inform the mechanisms and potential clinical utility of tDCS. A new tDCS technique, high
      definition (HD) tDCS, offers more focal stimulation than conventional tDCS (C-tDCS). The
      degree to which C-tDCS or HD-tDCS engage dorsal prefrontal-limbic neural circuits is unknown,
      yet is vital for understanding, confirming and subsequently improving possible therapeutic
      effects. Innovative MRI techniques that are able to map tDCS currents in vivo and that track
      changes in regional cerebral blood flow occurring with tDCS over time can provide direct
      evidence of neural effects. Based on a) theoretical modeling of tDCS current flow, b) studies
      showing hypo-metabolism, decreased CBF or activity in dorsal prefrontal-limbic networks, c)
      modulation of these regions with treatment, and, c) our prior results showing significant
      relationships in between change in dACC rCBF and clinical response to electroconvulsive
      therapy (ECT), an established brain stimulation treatment, we will test for the tDCS
      engagement and modulation of the DLPFC and dACC using tDCS current mapping performed in vivo
      and perfusion MRI. MRI-guided neuronavigation will be used to optimize and standardize
      electrode placement for DLPFC stimulation.

      In this trial, using HD-tDCS that optimal target engagement of DLPFC and larger rCBF changes
      in the DLPFC and dACC compared to C-tDCS in the first part of the trial, we will define
      relationships between target engagement and change in mood and behavior. Patients with
      moderate to severe MDD (N=100, n=50 in each group) will be randomized to Active or Sham left
      anodal DLPFC HD-tDCS. Patients will complete MRI scans including tDCS current mapping and
      pCASL as well as two functional imaging tasks probing cognitive control and emotion
      negativity bias, recruiting prefrontal-limbic circuitry, before and after completing a 12-day
      trial of 20-minute tDCS sessions.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Active and Sham controlled
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: Double blind
measure: Measured joint longitudinal change in rCBF and mood scores over the tDCS trial
time frame: 3 weeks
description: Correlation between percent change in rCBF after the tDCS trial and percent change in depressive symptoms for active versus sham tDCS conditions
measure: Measured joint longitudinal change in regional brain activation and mood scores over the tDCS trial
time frame: 3 weeks
description: Correlation between percent change in regional brain activation for tasks probing cognitive control and emotion and percent change depressive symptoms for active versus sham tDCS conditions
measure: Measured magnetic fields and rCBF at baseline and change in mood scores over the tDCS trial
time frame: 3 weeks
description: Correlation between variations in magnetic fields and rCBF at baseline and clinical outcomes at the end of the tDCS treatment trial
arm group label: Active - HD tDCS
arm group type: Experimental
description: Participants randomized to this arm will receive 12 sessions of high definition tDCS (HD-tDCS) stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes.
arm group label: Sham - HD tDCS
arm group type: Sham Comparator
description: Participants randomized to this arm will receive 12 sessions of sham HD tDCS stimulation (Soterix Medical) delivered to the left dorsolateral prefrontal cortex for 20-30 minutes.
intervention type: Device
intervention name: Active - HD tDCS
description: Non-invasive neuromodulation using HD electrodes placed on the scalp to deliver a constant, low current at 2 mA.
arm group label: Active - HD tDCS
intervention type: Device
intervention name: Sham - HD tDCS
description: Sham neuromodulation using HD electrodes placed on the scalp to deliver a low current ramped up/down for 20 sec.
arm group label: Sham - HD tDCS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Katherine L Narr, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
last name: Suzanne Kozikowski, MS
phone: (424) 402-9051
email: DGCNeurostimStudy@mednet.ucla.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, Los Angeles
investigator full name: Katherine Narr
investigator title: Professor, Department of Neurology, Psychiatry and Biobehavioral Sciences
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No