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/NCT06003309</url>
    </required_header>
    <id_info>
      <org_study_id>807836</org_study_id>
      <nct_id>NCT06003309</nct_id>
    </id_info>
    <brief_title>Frequency and E-field Enhancement of ITBS for Depression (FREED)</brief_title>
    <acronym>FREED</acronym>
    <official_title>Frequency and E-field Enhancement of ITBS for Depression (FREED)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of California, San Diego</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institutes of Health (NIH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of California, San Diego</source>
    <oversight_info>
      <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>
        The investigators propose a randomized 3-arm double-blinded parallel experimental trial (20&#xD;
        sessions over 4 weeks) in 75 patients with TRD. The three arms include (1) the combination of&#xD;
        a fully individualized form of iTBS (using BOTH the frequency and E-field targeting&#xD;
        approaches) (Ind-iTBS)), (2) iTBS individualized using E-field targeting only (targeted-iTBS)&#xD;
        and (3) Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3&#xD;
        method). EEG data will be collected at rest and during a working memory task, at baseline,&#xD;
        and at the end of treatment along with clinical assessments of depression severity. The&#xD;
        target engagement dependent variable of interest in these three arms will be fronto-parietal&#xD;
        theta connectivity measured through resting-state EEG. The investigators hypothesize that&#xD;
        stimulation with Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity&#xD;
        than that produced with targeted-TBS and standard iTBS. Aim: To evaluate the effects of two&#xD;
        individualized forms of iTBS (i.e., using BOTH the frequency and E-field individualization;&#xD;
        Ind-iTBS) compared to iTBS individualized for E-field targeting only (targeted-iTBS) and&#xD;
        standard iTBS on fronto-parietal theta connectivity. Hypotheses: (1) Ind-iTBS will lead to&#xD;
        greater changes in fronto-parietal theta connectivity compared to both targeted-iTBS and&#xD;
        standard iTBS. (2) Ind-iTBS will also lead to a greater reduction in depressive symptoms (as&#xD;
        defined by the mean reduction in Montgomery Åsberg Depression Rating Scale Scores (MADRS))&#xD;
        compared to both targeted-iTBS and standard iTBS.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">April 1, 2025</completion_date>
    <primary_completion_date type="Anticipated">April 1, 2025</primary_completion_date>
    <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change from pre-treatment in fronto-parietal theta connectivity at post-treatment</measure>
      <time_frame>pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)</time_frame>
      <description>Source-localized fronto-parietal theta connectivity will be calculated from resting EEG</description>
    </primary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">75</enrollment>
    <condition>Major Depressive Disorder</condition>
    <arm_group>
      <arm_group_label>The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>iTBS individualized using E-field targeting only (targeted-iTBS)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method)</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS</intervention_name>
      <description>Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.</description>
      <arm_group_label>The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Transcranial Magnetic Stimulation (TMS) - targeted-iTBS</intervention_name>
      <description>Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting.</description>
      <arm_group_label>iTBS individualized using E-field targeting only (targeted-iTBS)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Transcranial Magnetic Stimulation (TMS) - Standard-iTBS</intervention_name>
      <description>Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. The standard iTBS will be delivered with the typical 5Hz/50Hz patterned frequencies used in the FDA approved treatment protocol and stimulation will be delivered according to the Beam F3 targeting.</description>
      <arm_group_label>Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Diagnosis of major depressive episode (MDE, in accordance with the Diagnostic and&#xD;
               Statistical Manual of Mental Disorders 5th edition (DSM-5), in the context of unipolar&#xD;
               major depressive disorder disorder.&#xD;
  &#xD;
            -  18-80 years of age.&#xD;
  &#xD;
            -  Male or female.&#xD;
  &#xD;
            -  At least one failed antidepressant medication trial at level 3 in the Antidepressant&#xD;
               Treatment History Form: Short Form (ATHF-SF) classification.&#xD;
  &#xD;
            -  Montgomery-Asberg Depression Rating Scale (MADRS) Score of &gt;19 (moderate - severe&#xD;
               depression).&#xD;
  &#xD;
            -  No increase or initiation of new antidepressant therapy in the four weeks prior to&#xD;
               screening.&#xD;
  &#xD;
            -  Demonstrated capacity to give informed consent.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Inability to provide informed consent.&#xD;
  &#xD;
            -  Medically unstable patients.&#xD;
  &#xD;
            -  Concomitant neurological disorder or a history of a seizure disorder.&#xD;
  &#xD;
            -  Patients who are pregnant or breastfeeding.&#xD;
  &#xD;
            -  Any psychotic disorder or current active psychotic symptoms.&#xD;
  &#xD;
            -  Patients who have intracranial implants, other medical device or condition deemed&#xD;
               unsafe for TMS.&#xD;
  &#xD;
            -  Contraindication to MRI scanning.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>80 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Interventional Psychiatry</last_name>
      <phone>858-207-0938</phone>
      <email>iptrials@health.ucsd.edu</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University of California, San Diego</investigator_affiliation>
      <investigator_full_name>Zafiris Daskalakis</investigator_full_name>
      <investigator_title>Chair of Psychiatry Department</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>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- 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/NCT06003309
  org study id: 807836
  nct id: NCT06003309
  lead sponsor: 
  collaborator: 
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  The investigators propose a randomized 3-arm double-blinded parallel experimental trial (20
        sessions over 4 weeks) in 75 patients with TRD. The three arms include (1) the combination of
        a fully individualized form of iTBS (using BOTH the frequency and E-field targeting
        approaches) (Ind-iTBS)), (2) iTBS individualized using E-field targeting only (targeted-iTBS)
        and (3) Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3
        method). EEG data will be collected at rest and during a working memory task, at baseline,
        and at the end of treatment along with clinical assessments of depression severity. The
        target engagement dependent variable of interest in these three arms will be fronto-parietal
        theta connectivity measured through resting-state EEG. The investigators hypothesize that
        stimulation with Ind-iTBS will lead to greater changes in fronto-parietal theta connectivity
        than that produced with targeted-TBS and standard iTBS. Aim: To evaluate the effects of two
        individualized forms of iTBS (i.e., using BOTH the frequency and E-field individualization;
        Ind-iTBS) compared to iTBS individualized for E-field targeting only (targeted-iTBS) and
        standard iTBS on fronto-parietal theta connectivity. Hypotheses: (1) Ind-iTBS will lead to
        greater changes in fronto-parietal theta connectivity compared to both targeted-iTBS and
        standard iTBS. (2) Ind-iTBS will also lead to a greater reduction in depressive symptoms (as
        defined by the mean reduction in Montgomery Åsberg Depression Rating Scale Scores (MADRS))
        compared to both targeted-iTBS and standard iTBS.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Change from pre-treatment in fronto-parietal theta connectivity at post-treatment
  time frame: pre-treatment (within 24 hours prior to first treatment) and post-treatment (within 72 hours of final treatment)
  description: Source-localized fronto-parietal theta connectivity will be calculated from resting EEG
  arm group label: The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches)
  arm group type: Active Comparator
  arm group label: iTBS individualized using E-field targeting only (targeted-iTBS)
  arm group type: Active Comparator
  arm group label: Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method)
  arm group type: Active Comparator
  intervention type: Device
  intervention name: Transcranial Magnetic Stimulation (TMS) - Fully Individualized iTBS
  description: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the Ind-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting. The stimulation frequency will also be individualized according to EEG-derived TGC.
  arm group label: The fully individualized form of iTBS (BOTH the frequency and E-field targeting approaches)
  intervention type: Device
  intervention name: Transcranial Magnetic Stimulation (TMS) - targeted-iTBS
  description: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. In the targeted-iTBS, the coil placement and current amplitude will be provided using individualized E-field modelling and coordinate-based cortical targeting.
  arm group label: iTBS individualized using E-field targeting only (targeted-iTBS)
  intervention type: Device
  intervention name: Transcranial Magnetic Stimulation (TMS) - Standard-iTBS
  description: Repetitive transcranial magnetic stimulation (rTMS) is a safe and effective treatment for TRD that is increasingly being used in clinical practice across the world. It's mechanism of action is based on Farady Law of electromagnetic induction where the magnetic field produced by TMS coil induces electric field in the neurons. The standard iTBS will be delivered with the typical 5Hz/50Hz patterned frequencies used in the FDA approved treatment protocol and stimulation will be delivered according to the Beam F3 targeting.
  arm group label: Standard iTBS treatment (i.e., typical iTBS localized to the DLPFC using the Beam F3 method)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 80 Years
  healthy volunteers: No
  last name: Interventional Psychiatry
  phone: 858-207-0938
  email: iptrials@health.ucsd.edu
  responsible party type: Principal Investigator
  investigator affiliation: University of California, San Diego
  investigator full name: Zafiris Daskalakis
  investigator title: Chair of Psychiatry Department
  mesh term: Depressive Disorder
  mesh term: Depressive Disorder, Major
  sharing ipd: No