<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/NCT04485455</url>
  </required_header>
  <id_info>
    <org_study_id>19-1100</org_study_id>
    <nct_id>NCT04485455</nct_id>
  </id_info>
  <brief_title>iTBS for Adolescent Depression: An Open Label Study Evaluating Safety and Efficacy of Treatment</brief_title>
  <official_title>Open Label Study of the Efficacy, Durability, Safety and Feasibility of Intermittent Theta Burst Stimulation (iTBS) in Adolescents With Major Depressive Disorder: Effect Duration, Suicidality, and Non-Suicidal Self Injurious Behavior</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of North Carolina, Chapel Hill</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open label, pilot, feasibility study evaluating effects of Intermittent Theta&#xD;
      Burst Transcranial Magnetic Stimulation (iTBS) on 5 eligible adolescents for the treatment of&#xD;
      depression. Safety and tolerability will be evaluated with changes in depression scores, and&#xD;
      suicidality and non-suicidal self injurious behavior will also be monitored for exploratory&#xD;
      and safety measures.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will investigate the efficacy and durability of the effects of Intermittent Theta&#xD;
      Burst Stimulation (iTBS) in adolescent depression by measuring changes in clinical ratings&#xD;
      before, during, and after 4 weeks of treatment, up to 12 weeks following treatment. The&#xD;
      investigators expect that subjects will show: improvement in symptoms over 20 iTBS sessions&#xD;
      as measured by the Children's Depression Rating Scale Revised (CDRS-R), Hamilton Depression&#xD;
      Rating Scale (HAM-D) and Non-suicidal Self Injurious Behavior (NSSIB) measures, and&#xD;
      persistence of this reduction of depressive symptoms through the 12 weeks follow up period of&#xD;
      the study. In this study, the investigators will investigate the safety of the effects of&#xD;
      iTBS in adolescent depression. The investigators will investigate safety of the treatment&#xD;
      regimen by assessing suicidality. The investigators expect suicidal thoughts and behavior&#xD;
      will reduce with iTBS treatment as measured by the Columbia Suicide Severity Rating Scale&#xD;
      (C-SSRS) and a psychiatrist's clinical assessment. The investigators also expect that those&#xD;
      with NSSIB at the start of the trial will have less after iTBS treatments. The investigators&#xD;
      do not expect any change in cognition measured with the Mini Mental Status Exam (MMSE),&#xD;
      Trails B, and List Generation. The investigators will investigate treatment feasibility by&#xD;
      assessing treatment completion and withdrawal. The investigators define the feasibility of&#xD;
      iTBS will be defined as feasible by as completion of 15/20 (75%) iTBS treatment sessions by&#xD;
      all subjects and withdrawal from treatment of no more than one of five subjects (20%) due to&#xD;
      intolerable side effects or persistent symptoms of MDD. Investigation of efficacy,&#xD;
      durability, safety as well as feasibility simultaneously is essential in this preliminary&#xD;
      study of the use of iTBS in adolescents in order to justify a larger future study. This study&#xD;
      will include a screening visit, 20 iTBS treatments, and 3 planned follow up visits.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 21, 2020</start_date>
  <completion_date type="Actual">July 29, 2021</completion_date>
  <primary_completion_date type="Actual">April 30, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HAM-D Score From Baseline to Week 1</measure>
    <time_frame>Baseline, Week 1</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CDRS-R Score From Baseline to Week 1</measure>
    <time_frame>Baseline, Week 1</time_frame>
    <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in HAM-D Score From Baseline to Week 2</measure>
    <time_frame>Baseline, Week 2</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CDRS-R Score From Baseline to Week 2</measure>
    <time_frame>Baseline, Week 2</time_frame>
    <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in HAM-D Score From Baseline to Week 3</measure>
    <time_frame>Baseline, Week 3</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CDRS-R Score From Baseline to Week 3</measure>
    <time_frame>Baseline, Week 3</time_frame>
    <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in HAM-D Score From Baseline to Week 4</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in CDRS-R Score From Baseline to Week 4</measure>
    <time_frame>Baseline, Week 4</time_frame>
    <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Occurrences of Passive Suicidal Ideation</measure>
    <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
    <description>Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has &quot;yes or no&quot; answers to assess the likelihood of a subject harming themselves, including &quot;yes/no&quot; to passive suicidal ideation. Participants indicating a &quot;yes&quot; response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Completed the Study</measure>
    <time_frame>Up to Week 5</time_frame>
    <description>Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Withdrew From the Study</measure>
    <time_frame>Up to Week 5</time_frame>
    <description>Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of Treatment Effect With HAM-D Scores</measure>
    <time_frame>From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
    <description>Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Durability of Treatment Effect With CDRS-R Scores</measure>
    <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
    <description>Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI</measure>
    <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
    <description>Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>iTBS Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Teenage participants with depression will receive iTBS therapy using a Transcranial Magnetic Stimulation (TMS) protocol delivering electro-magnetic stimulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>iTBS Device/Motor Threshold Coil</intervention_name>
    <description>Motor Threshold determination, done prior to starting treatments, determines the location and the intensity for the iTBS treatments. A magnetic field is applied with increasing intensity stimulating the motor region of the brain until there is thumb movement; this indicates the intensity of the treatments; the location for treatment is in the sensory area parallel to this location.</description>
    <arm_group_label>iTBS Therapy</arm_group_label>
    <other_name>MagProX100 with MagOption Stimulator and Magpro Coil C-B60 or C-B70</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>iTBS Device/Treatment Coil</intervention_name>
    <description>iTBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz very quickly). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatments lasts approximately 3 minutes, and sessions are provided 20 times (Monday-Friday for 4 consecutive weeks).</description>
    <arm_group_label>iTBS Therapy</arm_group_label>
    <other_name>MagPro, Models R30 with MagOption, X100 WITH MagOption, Coil Cool-B65</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A score of greater than 40 on the CDRS-R and 17 on HAM-D.&#xD;
&#xD;
          -  Documentation of DSM-V criteria for current MDD or TRD will be required for study&#xD;
             entry.&#xD;
&#xD;
          -  Patients may be on antidepressant medication at a stable dose or receiving&#xD;
             psychotherapy with a licensed provider during the active phase of TMS treatment for 4&#xD;
             weeks.&#xD;
&#xD;
          -  Ability to provide consent and take part in questionnaires and scales (i.e.: not&#xD;
             currently intellectually disabled).&#xD;
&#xD;
          -  The presence of suicidality or NSSIB are not required to enter this study. Although&#xD;
             our secondary end-points include suicidality, and the investigators are also exploring&#xD;
             NSSIB, and thus this may not lead to many data, the investigators' plan is to use data&#xD;
             from this study to justify a larger study where this can be more robustly&#xD;
             investigated.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past or current diagnosis of bipolar disorder, psychosis, seizures or traumatic brain&#xD;
             injury.&#xD;
&#xD;
          -  Presence of intracranial metallic implants or fragments, which is a contraindication&#xD;
             for TMS.&#xD;
&#xD;
          -  Lifetime history of (or currently present) epilepsy.&#xD;
&#xD;
          -  Current diagnosis of substance abuse, eating disorder, PTSD (Post Traumatic Stress&#xD;
             Disorder), or intellectual disability.* Nicotine use disorder will not directly&#xD;
             preclude a potential subject from this study. Although chronic nicotine use does&#xD;
             effect central nervous system excitability, what would be more confounding to our&#xD;
             study would be if there is a sudden change in nicotine use during the treatment phase,&#xD;
             as this may affect the motor threshold. Inclusion will however be at the PI's&#xD;
             discretion.&#xD;
&#xD;
          -  Current imminent suicide ideation or other clinical reasons for inpatient psychiatric&#xD;
             hospitalization.&#xD;
&#xD;
          -  Currently pregnant. There is currently not adequate data from this population to&#xD;
             ensure safety with the scope of this protocol.&#xD;
&#xD;
          -  Any reason the investigator determines may cause noncompliance with study rules or is&#xD;
             unfit for receiving treatment.&#xD;
&#xD;
          -  Currently taking certain medications including antidepressants, stimulants,&#xD;
             benzodiazepines, and antipsychotics, antiepileptic (per investigator discretion).&#xD;
&#xD;
          -  Any positive drug testing from a urine drug test unless medically indicated with a&#xD;
             valid prescription.&#xD;
&#xD;
               -  Those with marijuana/cannabis positive results may retest later if at that time&#xD;
                  they do not meet criteria for substance abuse at screening and agree to refrain&#xD;
                  from use for the duration of study participation. Decision to be made by&#xD;
                  Investigator discretion.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>13 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shahzad Ali, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill-Psychiatry Outpatient Clinic</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 21, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 24, 2020</study_first_posted>
  <results_first_submitted>October 20, 2021</results_first_submitted>
  <results_first_submitted_qc>November 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 30, 2021</results_first_posted>
  <last_update_submitted>November 29, 2021</last_update_submitted>
  <last_update_submitted_qc>November 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Adolescent Depression</keyword>
  <keyword>Teen 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>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_time_frame>9 to 36 months following publication</ipd_time_frame>
    <ipd_access_criteria>Approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.</ipd_access_criteria>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 3, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT04485455/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>September 29, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/55/NCT04485455/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>iTBS Open Label</title>
          <description>All subjects enrolled into this study were in the same group, with all receiving active Intermittent Theta Burst Stimulation (iTBS) treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>iTBS Open Label</title>
          <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <title>13 to 17 year old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.2" lower_limit="13" upper_limit="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Age 17</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Age 13</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex/Gender, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Female</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Male</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Binary</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Depression HAM-D Rating Score</title>
          <description>Depression rating is determined by (Hamilton Depression Rating Scale) HAM-D assessments. A higher score indicates more severe depression rating. Scores can range from 0-52.</description>
          <units>Score on scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.8" lower_limit="8" upper_limit="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Mean Depression CDRS-R Rating Score</title>
          <description>Depression rating is determined by Children's Depression Rating Score Revised (CDRS-R) assessments. A higher score indicates more severe depression rating. Scores for this assessment range from 17-113.</description>
          <units>Score on an assessment</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="65.2" lower_limit="50" upper_limit="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in HAM-D Score From Baseline to Week 1</title>
        <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
        <time_frame>Baseline, Week 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HAM-D Score From Baseline to Week 1</title>
          <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.6" lower_limit="-15" upper_limit="-0.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in CDRS-R Score From Baseline to Week 1</title>
        <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
        <time_frame>Baseline, Week 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CDRS-R Score From Baseline to Week 1</title>
          <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.0" lower_limit="-15" upper_limit="-3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in HAM-D Score From Baseline to Week 2</title>
        <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
        <time_frame>Baseline, Week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HAM-D Score From Baseline to Week 2</title>
          <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.2" lower_limit="-13" upper_limit="0.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in CDRS-R Score From Baseline to Week 2</title>
        <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
        <time_frame>Baseline, Week 2</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CDRS-R Score From Baseline to Week 2</title>
          <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16" lower_limit="-24" upper_limit="-7.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in HAM-D Score From Baseline to Week 3</title>
        <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
        <time_frame>Baseline, Week 3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HAM-D Score From Baseline to Week 3</title>
          <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.2" lower_limit="-15" upper_limit="-3.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in CDRS-R Score From Baseline to Week 3</title>
        <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
        <time_frame>Baseline, Week 3</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CDRS-R Score From Baseline to Week 3</title>
          <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11" lower_limit="-22" upper_limit="-0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in HAM-D Score From Baseline to Week 4</title>
        <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in HAM-D Score From Baseline to Week 4</title>
          <description>The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.8" lower_limit="-14" upper_limit="-1.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in CDRS-R Score From Baseline to Week 4</title>
        <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
        <time_frame>Baseline, Week 4</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in CDRS-R Score From Baseline to Week 4</title>
          <description>The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14" lower_limit="-23" upper_limit="-4.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Occurrences of Passive Suicidal Ideation</title>
        <description>Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has &quot;yes or no&quot; answers to assess the likelihood of a subject harming themselves, including &quot;yes/no&quot; to passive suicidal ideation. Participants indicating a &quot;yes&quot; response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study.</description>
        <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Occurrences of Passive Suicidal Ideation</title>
          <description>Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has &quot;yes or no&quot; answers to assess the likelihood of a subject harming themselves, including &quot;yes/no&quot; to passive suicidal ideation. Participants indicating a &quot;yes&quot; response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study.</description>
          <units>Occurrences passive suicidal ideation</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Completed the Study</title>
        <description>Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
        <time_frame>Up to Week 5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Completed the Study</title>
          <description>Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Withdrew From the Study</title>
        <description>Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
        <time_frame>Up to Week 5</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Withdrew From the Study</title>
          <description>Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durability of Treatment Effect With HAM-D Scores</title>
        <description>Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
        <time_frame>From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Durability of Treatment Effect With HAM-D Scores</title>
          <description>Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Follow Up Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.8" lower_limit="-14" upper_limit="-3.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11" lower_limit="-17" upper_limit="-3.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.4" lower_limit="-15" upper_limit="-4.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Durability of Treatment Effect With CDRS-R Scores</title>
        <description>Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
        <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Durability of Treatment Effect With CDRS-R Scores</title>
          <description>Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Follow Up Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21" lower_limit="-33" upper_limit="-7.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19" lower_limit="-32" upper_limit="-6.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23" lower_limit="-34" upper_limit="-12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI</title>
        <description>Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit.</description>
        <time_frame>Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>iTBS Open Label</title>
            <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI</title>
          <description>Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit.</description>
          <units>Occurrences self-harm behavior</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Treatment Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Follow Up Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From date of informed consent to completion of study, which is the last follow-up visit, an approximate total of 16 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>iTBS Open Label</title>
          <description>All subjects enrolled into this study were in the same group, with all receiving active iTBS treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Fever - mild</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Scalp Pain - mild</sub_title>
                <counts group_id="E1" events="8" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Scalp Pain - moderate</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Ear Pain - mild</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Jaw Twitching - mild</sub_title>
                <counts group_id="E1" events="12" subjects_affected="5" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Jaw Twitching - moderate</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Tingling</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Right arm twitch - moderate</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Right arm twitch - mild</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Eyebrow twitching - mild</sub_title>
                <counts group_id="E1" events="9" subjects_affected="3" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Eye twitching - moderate</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Arm soreness - moderate</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Arm soreness - mild</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Migraine - severe</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Headache - mild</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
              <event>
                <sub_title>Headache- moderate</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety in social setting - mild</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Burn on shoulder - moderate</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Shahzad Ali, MD</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>984-974-0033</phone>
      <email>shali@med.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT04485455
org study id: 19-1100
nct id: NCT04485455
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
This is an open label, pilot, feasibility study evaluating effects of Intermittent Theta
      Burst Transcranial Magnetic Stimulation (iTBS) on 5 eligible adolescents for the treatment of
      depression. Safety and tolerability will be evaluated with changes in depression scores, and
      suicidality and non-suicidal self injurious behavior will also be monitored for exploratory
      and safety measures.
This study will investigate the efficacy and durability of the effects of Intermittent Theta
      Burst Stimulation (iTBS) in adolescent depression by measuring changes in clinical ratings
      before, during, and after 4 weeks of treatment, up to 12 weeks following treatment. The
      investigators expect that subjects will show: improvement in symptoms over 20 iTBS sessions
      as measured by the Children's Depression Rating Scale Revised (CDRS-R), Hamilton Depression
      Rating Scale (HAM-D) and Non-suicidal Self Injurious Behavior (NSSIB) measures, and
      persistence of this reduction of depressive symptoms through the 12 weeks follow up period of
      the study. In this study, the investigators will investigate the safety of the effects of
      iTBS in adolescent depression. The investigators will investigate safety of the treatment
      regimen by assessing suicidality. The investigators expect suicidal thoughts and behavior
      will reduce with iTBS treatment as measured by the Columbia Suicide Severity Rating Scale
      (C-SSRS) and a psychiatrist's clinical assessment. The investigators also expect that those
      with NSSIB at the start of the trial will have less after iTBS treatments. The investigators
      do not expect any change in cognition measured with the Mini Mental Status Exam (MMSE),
      Trails B, and List Generation. The investigators will investigate treatment feasibility by
      assessing treatment completion and withdrawal. The investigators define the feasibility of
      iTBS will be defined as feasible by as completion of 15/20 (75%) iTBS treatment sessions by
      all subjects and withdrawal from treatment of no more than one of five subjects (20%) due to
      intolerable side effects or persistent symptoms of MDD. Investigation of efficacy,
      durability, safety as well as feasibility simultaneously is essential in this preliminary
      study of the use of iTBS in adolescents in order to justify a larger future study. This study
      will include a screening visit, 20 iTBS treatments, and 3 planned follow up visits.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in HAM-D Score From Baseline to Week 1
time frame: Baseline, Week 1
description: The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
measure: Change in CDRS-R Score From Baseline to Week 1
time frame: Baseline, Week 1
description: The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
measure: Change in HAM-D Score From Baseline to Week 2
time frame: Baseline, Week 2
description: The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
measure: Change in CDRS-R Score From Baseline to Week 2
time frame: Baseline, Week 2
description: The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
measure: Change in HAM-D Score From Baseline to Week 3
time frame: Baseline, Week 3
description: The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
measure: Change in CDRS-R Score From Baseline to Week 3
time frame: Baseline, Week 3
description: The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
measure: Change in HAM-D Score From Baseline to Week 4
time frame: Baseline, Week 4
description: The Hamilton Rating Scale for Depression (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
measure: Change in CDRS-R Score From Baseline to Week 4
time frame: Baseline, Week 4
description: The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
measure: Number of Occurrences of Passive Suicidal Ideation
time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
description: Columbia Suicide Severity Rating Scale (C-SSRS) is a semi-structured interview that has "yes or no" answers to assess the likelihood of a subject harming themselves, including "yes/no" to passive suicidal ideation. Participants indicating a "yes" response to any of these questions were reported as having passive suicidal ideation. Each participant was assessed at 8 timepoints during the study.
measure: Number of Participants Who Completed the Study
time frame: Up to Week 5
description: Feasibility for this protocol is partially determined by completion rate. Treatment completion is defined in this protocol by 75% of treatments completed (15/20) per subject. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).
measure: Number of Participants Who Withdrew From the Study
time frame: Up to Week 5
description: Feasibility for this protocol is partially determined by withdrawal rate. Withdrawal is defined as no more than 1 out of 5 subjects (20% of participants) withdrawing due to intolerable side effects caused by treatment or persistent depressive symptoms. This will be measured through completion of Week 4 of treatment (Week 5 of protocol when including screening phase).
measure: Durability of Treatment Effect With HAM-D Scores
time frame: From Baseline up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
description: Change in scores of Hamilton Depression Rating Scale (HAM-D) will be evaluated comparing Baseline to each follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The (HAM-D) total score comprises a sum of the 17 individual item scores which ranges from 0 to 52. Higher scores indicate a greater degree of depression.
measure: Durability of Treatment Effect With CDRS-R Scores
time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
description: Change in scores of Children Depression Rating Scale Revised (CDRS-R) during follow-up phase at 1 week, 4 weeks, and 12 weeks post-treatment. The Children's Depression Rating Scale-Revised (CDRS-R) total score ranges from 17 (minimal or no symptoms of depression) to 113 (indicative of depression) is a semi-structured, clinician-rated instrument designed for use with children and adolescents between the ages of 6 to 17 years of age and their caregivers. The CDRS-R evaluates the presence and severity of symptoms commonly associated with depression in childhood.
measure: Number of Occurrences of Non-Suicidal Self Injurious Behavior Through SITBI
time frame: Up to 12 Weeks Post-Treatment Completion, a total of up to 16 weeks
description: Self Injurious Thoughts and Behavior Interview (SITBI) is a semi-structured interview commonly used and administered by a clinician to determine if self-harm behavior has been present since the last visit. This will be evaluated at baseline (screening), once per week during the treatment phase, and at each follow up visit.
arm group label: iTBS Therapy
arm group type: Experimental
description: Teenage participants with depression will receive iTBS therapy using a Transcranial Magnetic Stimulation (TMS) protocol delivering electro-magnetic stimulation
intervention type: Device
intervention name: iTBS Device/Motor Threshold Coil
description: Motor Threshold determination, done prior to starting treatments, determines the location and the intensity for the iTBS treatments. A magnetic field is applied with increasing intensity stimulating the motor region of the brain until there is thumb movement; this indicates the intensity of the treatments; the location for treatment is in the sensory area parallel to this location.
arm group label: iTBS Therapy
other name: MagProX100 with MagOption Stimulator and Magpro Coil C-B60 or C-B70
intervention type: Device
intervention name: iTBS Device/Treatment Coil
description: iTBS is a particular TMS protocol which delivers the magnetic field in triplet bursts (three stimulations very close together at a frequency of 50 Hz very quickly). The triplet bursts are repeated at a rate of 5 Hz for 2 seconds (30 pulses), followed by 8 seconds rest, repeated 20 times for a total of 600 pulses. Each treatments lasts approximately 3 minutes, and sessions are provided 20 times (Monday-Friday for 4 consecutive weeks).
arm group label: iTBS Therapy
other name: MagPro, Models R30 with MagOption, X100 WITH MagOption, Coil Cool-B65
criteria: 
gender: All
minimum age: 13 Years
maximum age: 17 Years
healthy volunteers: No
last name: Shahzad Ali, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: Yes
ipd description: Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.
ipd info type: Study Protocol
ipd info type: Informed Consent Form (ICF)
ipd time frame: 9 to 36 months following publication
ipd access criteria: Approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 