xml: <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/NCT05996900</url>
    </required_header>
    <id_info>
      <org_study_id>132074</org_study_id>
      <nct_id>NCT05996900</nct_id>
    </id_info>
    <brief_title>Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans</brief_title>
    <official_title>Investigating the Neural Mechanisms of Repetitive Brain Stimulation With Invasive and Noninvasive Electrophysiology in Humans</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Stanford University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>University of Iowa</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>Massachusetts General Hospital</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Stanford University</source>
    <oversight_info>
      <has_dmc>Yes</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>
        Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but&#xD;
        clinical outcome is suboptimal, partially because investigators are missing&#xD;
        biologically-grounded brain markers which show that TMS is modifying activity at the intended&#xD;
        target in the brain. The goal of this proposal is to characterize the key markers of the&#xD;
        brain's response to repeated doses of TMS with high resolution using invasive brain&#xD;
        recordings in humans, and relate these brain markers to noninvasive recordings. These markers&#xD;
        will improve the understanding of TMS and can be used to optimize and enhance clinical&#xD;
        efficacy for depression and other psychiatric disorders.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major&#xD;
        depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are&#xD;
        unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of&#xD;
        the brain to make these changes is referred to as plasticity. rTMS-induced changes are&#xD;
        thought to build with successive treatment sessions, a process referred to as metaplasticity.&#xD;
        While both plasticity and metaplasticity are well-established in single cell physiology,&#xD;
        relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators&#xD;
        need to understand 1) the neural response to a single rTMS session (plasticity), 2) the&#xD;
        neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether&#xD;
        computational models of plasticity based on single-cell physiology apply to human patients&#xD;
        receiving rTMS for depression.&#xD;
  &#xD;
        Goals of the study are to 1) establish a detailed mechanistic understanding of the brain&#xD;
        changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological&#xD;
        biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain&#xD;
        and clinical changes.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">July 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">January 1, 2027</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>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>TMS-iEEG change after one TBS session</measure>
      <time_frame>45 minutes</time_frame>
      <description>Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ES-iEEG change after one TBS session</measure>
      <time_frame>45 minutes</time_frame>
      <description>Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ES-iEEG change between two sequential TBS sessions</measure>
      <time_frame>45 minutes</time_frame>
      <description>Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TMS-iEEG change between two sequential TBS sessions</measure>
      <time_frame>45 minutes</time_frame>
      <description>Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.</description>
    </secondary_outcome>
    <number_of_arms>4</number_of_arms>
    <enrollment type="Anticipated">49</enrollment>
    <condition>Major Depressive Disorder</condition>
    <condition>Epilepsy</condition>
    <arm_group>
      <arm_group_label>TBS via direct electrical stimulation</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>TBS via transcranial magnetic stimulation</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham TBS via direct electrical stimulation</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham TBS via transcranial magnetic stimulation</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Intracranial electrodes</intervention_name>
      <description>Intracranial electrodes will be used for the delivery of invasive brain stimulation.</description>
      <arm_group_label>Sham TBS via direct electrical stimulation</arm_group_label>
      <arm_group_label>TBS via direct electrical stimulation</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>TMS</intervention_name>
      <description>TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.</description>
      <arm_group_label>Sham TBS via transcranial magnetic stimulation</arm_group_label>
      <arm_group_label>TBS via transcranial magnetic stimulation</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Men and women, ages 18 to 65&#xD;
  &#xD;
            -  Medication-refractory epilepsy requiring phase II monitoring&#xD;
  &#xD;
            -  Must have intellectual capacity to ensure adequate comprehension of the study and&#xD;
               potential risks involved in order to provide informed consent&#xD;
  &#xD;
            -  No current or history of major neurological disorders other than epilepsy&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Those with a contraindication for MRIs (e.g. implanted metal)&#xD;
  &#xD;
            -  Any unstable medical condition&#xD;
  &#xD;
            -  Neurological or uncontrolled medical disease&#xD;
  &#xD;
            -  Active substance abuse&#xD;
  &#xD;
            -  Currently pregnant or breastfeeding&#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_contact>
      <last_name>Jade Truong</last_name>
      <phone>(408) 840-3313</phone>
      <email>kellerlab@stanford.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 18, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 18, 2023</study_first_posted>
    <last_update_submitted>August 9, 2023</last_update_submitted>
    <last_update_submitted_qc>August 9, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 18, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Stanford University</investigator_affiliation>
      <investigator_full_name>Corey Keller</investigator_full_name>
      <investigator_title>Principal Investigator, Assistant Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Depressive Disorder</mesh_term>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05996900
  org study id: 132074
  nct id: NCT05996900
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but
        clinical outcome is suboptimal, partially because investigators are missing
        biologically-grounded brain markers which show that TMS is modifying activity at the intended
        target in the brain. The goal of this proposal is to characterize the key markers of the
        brain's response to repeated doses of TMS with high resolution using invasive brain
        recordings in humans, and relate these brain markers to noninvasive recordings. These markers
        will improve the understanding of TMS and can be used to optimize and enhance clinical
        efficacy for depression and other psychiatric disorders.
  Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major
        depressive disorder, but remission rates are 20-40%, and ideal stimulation parameters are
        unknown. rTMS is thought to work by changing the synaptic strength of neurons. The ability of
        the brain to make these changes is referred to as plasticity. rTMS-induced changes are
        thought to build with successive treatment sessions, a process referred to as metaplasticity.
        While both plasticity and metaplasticity are well-established in single cell physiology,
        relevance to rTMS in humans remains unknown. To improve clinical efficacy, the investigators
        need to understand 1) the neural response to a single rTMS session (plasticity), 2) the
        neural response to repeated daily rTMS sessions (metaplasticity), and 3) whether
        computational models of plasticity based on single-cell physiology apply to human patients
        receiving rTMS for depression.
  
        Goals of the study are to 1) establish a detailed mechanistic understanding of the brain
        changes during current rTMS treatment; 2) identify clinically meaningful electrophysiological
        biomarkers for rTMS treatment; 3) establish a computational model to help predict both brain
        and clinical changes.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Double (Participant, Outcomes Assessor)
  measure: TMS-iEEG change after one TBS session
  time frame: 45 minutes
  description: Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG (intracranial EEG) and/or sEEG (stereo EEG).
  measure: ES-iEEG change after one TBS session
  time frame: 45 minutes
  description: Change in evoked response measured after a single TBS session for active and sham, by resting state iEEG and/or sEEG.
  measure: ES-iEEG change between two sequential TBS sessions
  time frame: 45 minutes
  description: Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
  measure: TMS-iEEG change between two sequential TBS sessions
  time frame: 45 minutes
  description: Change in single-pulse evoked response, or cortico-cortical evoked potentials (CCEPs), measured between two sequential TBS sessions, by resting state iEEG and/or sEEG.
  arm group label: TBS via direct electrical stimulation
  arm group type: Active Comparator
  arm group label: TBS via transcranial magnetic stimulation
  arm group type: Active Comparator
  arm group label: Sham TBS via direct electrical stimulation
  arm group type: Sham Comparator
  arm group label: Sham TBS via transcranial magnetic stimulation
  arm group type: Sham Comparator
  intervention type: Device
  intervention name: Intracranial electrodes
  description: Intracranial electrodes will be used for the delivery of invasive brain stimulation.
  arm group label: Sham TBS via direct electrical stimulation
  arm group label: TBS via direct electrical stimulation
  intervention type: Device
  intervention name: TMS
  description: TMS will be used for the delivery of noninvasive brain stimulation both before and after implantation electrode surgery.
  arm group label: Sham TBS via transcranial magnetic stimulation
  arm group label: TBS via transcranial magnetic stimulation
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: No
  last name: Jade Truong
  phone: (408) 840-3313
  email: kellerlab@stanford.edu
  responsible party type: Principal Investigator
  investigator affiliation: Stanford University
  investigator full name: Corey Keller
  investigator title: Principal Investigator, Assistant Professor
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major