<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/NCT03275337</url>
  </required_header>
  <id_info>
    <org_study_id>2017_001_01</org_study_id>
    <nct_id>NCT03275337</nct_id>
  </id_info>
  <brief_title>Cerebellar Neuromodulation to Enhance Fear Extinction and Predict Response to Exposure Therapy</brief_title>
  <official_title>Cerebellar Neuromodulation to Enhance Fear Extinction and Predict Response to Exposure Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laureate Institute for Brain Research, Inc.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laureate Institute for Brain Research, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Emerging neuroimaging studies have shown that the cerebellum contributes to different aspects&#xD;
      of timing, prediction, learning, and extinction of conditioned responses to aversive stimuli,&#xD;
      factors that may be relevant to the success of exposure based behavioral therapy. Our goals&#xD;
      are to determine the cerebellar contributions to fear extinction by attempting to modulate&#xD;
      key pathways in this process by theta burst stimulation. The long term goal is to lay the&#xD;
      foundation for future studies in which neuromodulation is used to augment exposure therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants in this study will undergo an assessment for past history and present symptoms&#xD;
      of mood, anxiety, trauma, substance abuse, and eating disorders. Safety screening for&#xD;
      functional MRI (fMRI) and repetitive transcranial magnetic stimulation (rTMS) will be&#xD;
      performed prior to enrollment.&#xD;
&#xD;
      Phase 1 of the study involves two visits. The first visit involves undergoing an fMRI scan&#xD;
      and a motor thresholding procedure for rTMS. A clinical assessment will be performed for the&#xD;
      above symptoms, or a recap of symptoms if the participant had been previously assessed at our&#xD;
      institute.&#xD;
&#xD;
      The second visit involves a fear conditioning session performed in the fMRI scanner followed&#xD;
      by one session of rTMS over either a cerebellar or occipital lobe (control) target. This will&#xD;
      be immediately followed by a fear extinction phase, also in the fMRI scanner. The participant&#xD;
      will return in 24hours to determine consolidation of the fear extinction process.&#xD;
&#xD;
      Phase 2 is similar to Phase 1, except that each participant will undergo two sessions of the&#xD;
      fear conditioning and fear extinction phases while undergoing an fMRI scan. In one session,&#xD;
      they will receive rTMS over a cerebellar target. In the other session, they will receive rTMS&#xD;
      over a control site. These sessions will be separated by at least 1 week.&#xD;
&#xD;
      The participants will then undergo 10 weeks of exposure therapy for social phobia. The goal&#xD;
      is to determine whether neuroplasticity related to cerebellar stimulation can predict the&#xD;
      response to exposure therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2019</completion_date>
  <primary_completion_date type="Actual">December 31, 2019</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>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Activation of ventromedial prefrontal cortex after cerebellar stimulation</measure>
    <time_frame>Phase 1, Years 1-3</time_frame>
    <description>Activation of vmPFC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in resting state connectivity between vmPFC and cerebellar stimulation target</measure>
    <time_frame>Phase 1, Years 1-3</time_frame>
    <description>Change in resting state connectivity between vmPFC and cerebellum after cerebellar stimulation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes</measure>
    <time_frame>Phase 2, Years 3-5</time_frame>
    <description>Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Anxiety Disorders</condition>
  <condition>Social Phobia</condition>
  <arm_group>
    <arm_group_label>Anodal tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Anodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cathodal tDCS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cathodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tDCS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sham tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation</intervention_name>
    <description>tDCS is a non-invasive form of neuromodulation in which direct current is administered placed over a brain region of interest to induce physiological changes such as inhibition or excitation over that region.</description>
    <arm_group_label>Anodal tDCS</arm_group_label>
    <arm_group_label>Cathodal tDCS</arm_group_label>
    <arm_group_label>Sham tDCS</arm_group_label>
    <other_name>tDCS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Generalize Anxiety or Social Phobia with an OASIS score =&gt;8&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Safety concerns related to undergoing an fMRI scan or tDCS, such as metal in the head,&#xD;
             history of unprovoked seizures in self or a first-degree family member, medications&#xD;
             that reduce seizure threshold, pregnant or planning to become pregnant.&#xD;
&#xD;
          -  History of Post Traumatic Stress Disorder, Obsessive Compulsive Disorder, Panic&#xD;
             Disorder, Current Major Depressive Illness, Substance Abuse in the past 1-year, or any&#xD;
             thought disorder such as schizophrenia or bipolar disorder.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yoon-Hee Cha, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laureate Institute for Brain Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laureate Institute for Brain Research</name>
      <address>
        <city>Tulsa</city>
        <state>Oklahoma</state>
        <zip>74011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>August 28, 2020</last_update_submitted>
  <last_update_submitted_qc>August 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Social Phobia</keyword>
  <keyword>Anxiety</keyword>
  <keyword>Cerebellum</keyword>
  <keyword>tDCS</keyword>
  <keyword>Neuromodulation</keyword>
  <keyword>Fear Extinction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Phobia, Social</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 30, 2021</submitted>
    <returned>August 24, 2021</returned>
    <submitted>September 20, 2021</submitted>
    <returned>October 14, 2021</returned>
    <submitted>December 7, 2021</submitted>
    <returned>January 4, 2022</returned>
  </pending_results>
  <!-- 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/NCT03275337
org study id: 2017_001_01
nct id: NCT03275337
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Emerging neuroimaging studies have shown that the cerebellum contributes to different aspects
      of timing, prediction, learning, and extinction of conditioned responses to aversive stimuli,
      factors that may be relevant to the success of exposure based behavioral therapy. Our goals
      are to determine the cerebellar contributions to fear extinction by attempting to modulate
      key pathways in this process by theta burst stimulation. The long term goal is to lay the
      foundation for future studies in which neuromodulation is used to augment exposure therapy.
Participants in this study will undergo an assessment for past history and present symptoms
      of mood, anxiety, trauma, substance abuse, and eating disorders. Safety screening for
      functional MRI (fMRI) and repetitive transcranial magnetic stimulation (rTMS) will be
      performed prior to enrollment.

      Phase 1 of the study involves two visits. The first visit involves undergoing an fMRI scan
      and a motor thresholding procedure for rTMS. A clinical assessment will be performed for the
      above symptoms, or a recap of symptoms if the participant had been previously assessed at our
      institute.

      The second visit involves a fear conditioning session performed in the fMRI scanner followed
      by one session of rTMS over either a cerebellar or occipital lobe (control) target. This will
      be immediately followed by a fear extinction phase, also in the fMRI scanner. The participant
      will return in 24hours to determine consolidation of the fear extinction process.

      Phase 2 is similar to Phase 1, except that each participant will undergo two sessions of the
      fear conditioning and fear extinction phases while undergoing an fMRI scan. In one session,
      they will receive rTMS over a cerebellar target. In the other session, they will receive rTMS
      over a control site. These sessions will be separated by at least 1 week.

      The participants will then undergo 10 weeks of exposure therapy for social phobia. The goal
      is to determine whether neuroplasticity related to cerebellar stimulation can predict the
      response to exposure therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Activation of ventromedial prefrontal cortex after cerebellar stimulation
time frame: Phase 1, Years 1-3
description: Activation of vmPFC
measure: Change in resting state connectivity between vmPFC and cerebellar stimulation target
time frame: Phase 1, Years 1-3
description: Change in resting state connectivity between vmPFC and cerebellum after cerebellar stimulation
measure: Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes
time frame: Phase 2, Years 3-5
description: Baseline cerebellar-cerebral connectivity prediction of exposure therapy outcomes
arm group label: Anodal tDCS
arm group type: Experimental
description: Anodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.
arm group label: Cathodal tDCS
arm group type: Experimental
description: Cathodal tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.
arm group label: Sham tDCS
arm group type: Active Comparator
description: Sham tDCS will be performed over bilateral cerebellar hemispheres for 20-minutes.
intervention type: Device
intervention name: Transcranial Direct Current Stimulation
description: tDCS is a non-invasive form of neuromodulation in which direct current is administered placed over a brain region of interest to induce physiological changes such as inhibition or excitation over that region.
arm group label: Anodal tDCS
arm group label: Cathodal tDCS
arm group label: Sham tDCS
other name: tDCS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Yoon-Hee Cha, MD
role: Principal Investigator
affiliation: Laureate Institute for Brain Research
facility: 
country: United States
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Phobia, Social
sharing ipd: No
submitted: July 30, 2021
returned: August 24, 2021
submitted: September 20, 2021
returned: October 14, 2021
submitted: December 7, 2021
returned: January 4, 2022