<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/NCT04503096</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00100536</org_study_id>
    <nct_id>NCT04503096</nct_id>
  </id_info>
  <brief_title>Plasticity Using Stimulation and Habit: A Pilot Open-label rTMS Study for MCI</brief_title>
  <acronym>PUSH-Pilot</acronym>
  <official_title>High-dose Accelerated Repetitive Transcranial Magnetic Stimulation to Cognitive Control Neurocircuitry in Mild Cognitive Impairment: A Safety and Feasibility Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Center of Neuromodulation for Rehabilitation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this pilot study is to determine whether a high-dose form of non-invasive brain&#xD;
      stimulation is a promising and safe treatment for Mild Cognitive Impairment (MCI).&#xD;
      Transcranial magnetic stimulation (TMS) is an FDA approved treatment for depression. In&#xD;
      studies of TMS for depression and other disorders, individuals have experienced improved&#xD;
      cognitive function. Thus, the current study is testing whether TMS is safe, feasible and&#xD;
      effective in improving cognition in individuals with MCI.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 12, 2021</start_date>
  <completion_date type="Actual">July 27, 2022</completion_date>
  <primary_completion_date type="Actual">June 29, 2022</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>Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA)</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in the Review of Systems Criteria Compared to Baseline</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient Perception of Treatment Acceptability</measure>
    <time_frame>Administered at post-treatment</time_frame>
    <description>A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Retention Rate</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D)</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS)</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery</measure>
    <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
    <description>Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. The outcome measure reported below is the mean T-score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Mild Cognitive Impairment</condition>
  <arm_group>
    <arm_group_label>High-dose accelerated rTMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High-dose accelerated rTMS</intervention_name>
    <description>A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% resting motor threshold (rMT), intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
    <arm_group_label>High-dose accelerated rTMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age 60-85&#xD;
&#xD;
          -  English as a first/primary language&#xD;
&#xD;
          -  Has been diagnosed with MCI by a healthcare provider within the past two years per&#xD;
             National Institute on Aging - Alzheimer's Association (NIA-AA) criteria: (1) Concern&#xD;
             regarding cognitive decline reported by patient, informant, or clinician, (2)&#xD;
             Objective evidence of impairment for age in 1+ cognitive domains, typically memory,&#xD;
             (3) Preserved independent function, (4) no dementia.&#xD;
&#xD;
          -  Has met actuarial neuropsychological criteria for amnestic MCI: (1) ≥2 impaired scores&#xD;
             (i.e. ≤16th %ile) within one cognitive domain, or (2) ≥1 impaired scores (i.e. ≤16th&#xD;
             %ile) in ≥3 cognitive domains, using demographically-corrected normative data. (1) and&#xD;
             (2) must include the Memory domain.&#xD;
&#xD;
          -  The primary suspected etiology of amnestic MCI must be neurodegenerative, with&#xD;
             competing differential diagnoses (e.g. psychiatric disorder, movement disorder,&#xD;
             reversible causes, substance use) ruled out as the primary etiology/ies following a&#xD;
             clinical evaluation by a healthcare provider.&#xD;
&#xD;
          -  Ability to provide independent informed consent, consistent with the MCI diagnostic&#xD;
             criterion of preserved independent function.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Dementia diagnosis per the Diagnostic and Statistical Manual of Mental Disorders&#xD;
             (DSM-5) or NIA-AA criteria.&#xD;
&#xD;
          -  Daily/weekly use of anticholinergics, neuroleptics, sedatives, or bupropion. Stimulant&#xD;
             use may be allowed pending investigator review. Cholinesterase inhibitors, NMDA&#xD;
             receptor antagonists, and antidepressants are allowed if on a stable regimen of four&#xD;
             weeks prior to enrollment.&#xD;
&#xD;
          -  History of significant or unstable condition/s that may impact cognition such as&#xD;
             significant cardiac, cerebrovascular, or metabolic disease, severe mental illness&#xD;
             (e.g. bipolar disorder, psychoses), alcohol or substance use disorder, developmental&#xD;
             disorder, or other neurologic disease (e.g. severe brain injury, seizures).&#xD;
&#xD;
          -  MRI and TMS contraindications (e.g., implants, claustrophobia, conditions/treatments&#xD;
             that lower seizure threshold, taking medications that have short half-lives, no&#xD;
             quantifiable motor threshold, active substance use disorder, bipolar disorder).&#xD;
&#xD;
          -  Is enrolled in a clinical trial and/or has received an investigational medication&#xD;
             within the last 30 days.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Andreana Benitez, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Lisa McTeague, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>August 3, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <results_first_submitted>May 26, 2023</results_first_submitted>
  <results_first_submitted_qc>July 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 19, 2023</results_first_posted>
  <last_update_submitted>September 1, 2023</last_update_submitted>
  <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of South Carolina</investigator_affiliation>
    <investigator_full_name>Andreana Benitez</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>January 28, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT04503096/Prot_SAP_003.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>January 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT04503096/ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were referred by neurologists and neuropsychologists at MUSC's outpatient memory disorders and neuropsychology clinics. They were recruited between 12/22/2020 and 5/5/2022. The first participant was enrolled on 4/12/2021 and the last participant was enrolled on 6/1/2022.</recruitment_details>
      <pre_assignment_details>Of the 67 participants assessed for eligibility, 10 did not meet inclusion criteria, 15 met exclusion criteria, 17 declined to participate, and 1 was excluded for other reasons. 24 participants were assigned to treatment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>High-dose Accelerated rTMS</title>
          <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>High-dose Accelerated rTMS</title>
          <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="24"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74.1" spread="5.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </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>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="24"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montreal Cognitive Assessment (MoCA)</title>
          <description>The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance.</description>
          <population>This includes only participants with both pre- and post-treatment data.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="-1.25" spread="1.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Depression Rating Scale (HAM-D)</title>
          <description>The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms.</description>
          <population>This includes only participants with both pre- and post-treatment data.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value=".24" spread=".77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Geriatric Depression Scale (GDS)</title>
          <description>The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms.</description>
          <population>This includes only participants with both pre- and post-treatment data.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.55" spread="3.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Fluid Cognition Composite</title>
          <description>Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance.</description>
          <population>This includes only participants with both pre- and post-treatment data.</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.25" spread="8.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)</title>
        <description>Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)</title>
          <description>Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </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>Primary</type>
        <title>Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA)</title>
        <description>The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA)</title>
          <description>The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.20" spread="1.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>To monitor safety, paired t-tests were conducted to test for pre- to post-treatment differences in global cognition (i.e., MoCA z-scores).</non_inferiority_desc>
            <p_value>0.725</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in the Review of Systems Criteria Compared to Baseline</title>
        <description>A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Review of Systems Criteria Compared to Baseline</title>
          <description>A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Headache: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Headache: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scalp pain: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Scalp pain: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arm/hand pain: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Arm/hand pain: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other pain: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other pain: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weakness: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Weakness: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Loss of dexterity: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Loss of dexterity: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vision changes: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Vision changes: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hearing changes: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hearing changes: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ear ringing: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ear ringing: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea/Vomiting: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nausea/Vomiting: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite loss: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Appetite loss: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Rash: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin changes: Treatment day 1 (Baseline)</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Skin changes: Post-Treatment</title>
              <category_list>
                <category>
                  <title>Minimal/none (0-1)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Mild/moderate (2-3)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Marked/severe (4-5)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Patient Perception of Treatment Acceptability</title>
        <description>A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.</description>
        <time_frame>Administered at post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Perception of Treatment Acceptability</title>
          <description>A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&quot;I was motivated to attend the rTMS sessions.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="4" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;I was committed to completing the treatment course.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;I was interested in the rTMS techniques and learning about them.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;I understand the purpose of the treatment and how it could help my symptoms.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;I would be open to completing another course of rTMS treatment in the future, if needed.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;The rTMS treatment helped improve my ability to cope with daily challenges.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3" lower_limit="2" upper_limit="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Paraphrased: Condensed treatment was preferable to conventional treatment course</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;The staff members were attentive and sensitive to my needs during treatment.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;The staff members explained all procedures to me and answered my questions.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;There was plenty of flexibility in scheduling rTMS sessions around my other obligations.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5" lower_limit="5" upper_limit="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;At times I wanted to quit treatment.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;Treatment sessions were stressful.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;It was hard to stay awake during the rTMS sessions.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;I experienced pain and discomfort during treatment that was difficult to tolerate.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&quot;Completing multiple rTMS sessions in each day was at times tiring.&quot;</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" lower_limit="1" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Retention Rate</title>
        <description>Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>All participants who initiated treatment were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Retention Rate</title>
          <description>Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).</description>
          <population>All participants who initiated treatment were included in this analysis.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D)</title>
        <description>The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D)</title>
          <description>The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value=".33" spread=".91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Paired t-tests were conducted to test for pre- to post-treatment changes in depression using HAM-D raw scores.</non_inferiority_desc>
            <p_value>.605</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS)</title>
        <description>The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis. Of the 21 participants who completed treatment, one was missing a GDS score.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS)</title>
          <description>The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis. Of the 21 participants who completed treatment, one was missing a GDS score.</population>
          <units>scores on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.65" spread="3.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Paired t-tests were conducted to test for pre- to post-treatment changes in depression using GDS raw scores.</non_inferiority_desc>
            <p_value>.897</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery</title>
        <description>Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. The outcome measure reported below is the mean T-score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
        <time_frame>Baseline prior to treatment and at follow-up within 1 week post-treatment</time_frame>
        <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>High-dose Accelerated rTMS</title>
            <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery</title>
          <description>Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. The outcome measure reported below is the mean T-score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.</description>
          <population>Participants who completed both the pre- and post-treatment assessments were included in this analysis.</population>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.67" spread="7.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <non_inferiority_desc>Paired t-tests were conducted to test for pre- to post-treatment changes in cognition using Fluid Cognition Composite Scores.</non_inferiority_desc>
            <p_value>&lt; .001</p_value>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <desc>In this study, other (i.e., non-serious) adverse events were defined as those that were 1) unexpected, 2) related or possibly related to study participation, AND 3) serious or more prevalent than expected. This definition was approved by our local Institutional Review Board (IRB).</desc>
      <group_list>
        <group group_id="E1">
          <title>High-dose Accelerated rTMS</title>
          <description>High-dose accelerated rTMS: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% rMT, intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.</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="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="24"/>
              </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>Andreana Benitez PhD</name_or_title>
      <organization>Medical University of South Carolina</organization>
      <phone>(843) 876-8479</phone>
      <email>benitez@musc.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/NCT04503096
org study id: Pro00100536
nct id: NCT04503096
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The goal of this pilot study is to determine whether a high-dose form of non-invasive brain
      stimulation is a promising and safe treatment for Mild Cognitive Impairment (MCI).
      Transcranial magnetic stimulation (TMS) is an FDA approved treatment for depression. In
      studies of TMS for depression and other disorders, individuals have experienced improved
      cognitive function. Thus, the current study is testing whether TMS is safe, feasible and
      effective in improving cognition in individuals with MCI.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Clinically Significant Structural Brain Change on T1- and T2-weighted Magnetic Resonance Imaging (MRI)
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: Clinically significant structural brain change were determined by a board-certified neuroradiologist who reviewed both the pre-treatment and post-treatment structural (T1- and T2-weighted) MRI scans to identify the presence of any changes from pre- to post-treatment based on their clinical read of the images.
measure: Change From Baseline Global Cognition, as Measured by the Montreal Cognitive Assessment (MoCA)
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: The MoCA is a psychometrist-administered brief cognitive assessment tool with raw total scores ranging from 0 to 30, with higher values indicating better cognition. For this analysis raw total scores were converted to age- and education-adjusted Z-scores using published norms (Rossetti et al., 2011). Z-scores have a mean of 0 and a standard deviation of 1. Lower scores indicate worse performance. The outcome measure reported below is the mean Z-score score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.
measure: Change in the Review of Systems Criteria Compared to Baseline
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: A review of systems questionnaire will be administered to rate the subjective symptom (headache, scalp pain, arm/hand pain, other pain(s), numbness/tingling, other sensation(s), weakness, loss of dexterity, vision/hearing change(s), ear ringing, nausea/vomiting, appetite loss, rash, skin change(s) or any other symptom(s)) on a scale of 0 to 5 (none, minimal, mild, moderate, marked, severe).
measure: Patient Perception of Treatment Acceptability
time frame: Administered at post-treatment
description: A 15-item study-specific questionnaire of rTMS treatment acceptability, with each item rated on a scale from 1 to 5 (1 = not at all, 3 = somewhat, 5 = very much so). Higher scores indicate better acceptability for the first 10 items, lower scores indicate better acceptability for the last 5 items.
measure: Retention Rate
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: Percentage of participants who completed the study (n=21) relative to all participants who initiated treatment (n=22).
measure: Change From Baseline Depression, as Measured by the Hamilton Depression Rating Scale (HAM-D)
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: The Hamilton Depression Rating Scale (Ham-D) is a 17-item interviewer-administered structured questionnaire designed to assess symptoms of depression with scores ranging from 0 to 53, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.
measure: Change From Baseline Depression, as Measured by the Geriatric Depression Scale (GDS)
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: The Geriatric Depression Scale (GDS) is a 30-item scale that evaluates the severity of depressive symptoms in older adults with scores ranging from 0 to 30, with higher scores indicating more depressive symptoms. The outcome measure reported below is the mean score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.
measure: Change From Baseline Cognition, as Measured by the Fluid Cognition Composite Score From the NIH Toolbox Cognition Battery
time frame: Baseline prior to treatment and at follow-up within 1 week post-treatment
description: Fluid cognition was measured using the iPad-administered NIH Toolbox Cognition Battery (NIHTB-CB). Fluid Cognition Composite scores were calculated by averaging the demographically adjusted (age, education, sex, race/ethnicity; Casaletto et al., 2015) T-scores for 4 NIHTB-CB tests: the flanker inhibitory control, list sorting working memory, pattern comparison processing speed, and dimensional change card sort tests. T-Scores have a mean of 50 and a standard deviation of 10. Lower scores indicate worse performance. The outcome measure reported below is the mean T-score at the 1-week post-treatment assessment. The statistical analysis compares this mean score to the mean score at Baseline.
arm group label: High-dose accelerated rTMS
arm group type: Experimental
intervention type: Device
intervention name: High-dose accelerated rTMS
description: A MagVenture MagPro Transcranial Magnetic Stimulation (TMS) System will be utilized. All participants will receive open-label treatment for approximately eight, 3-minute sessions of intermittent theta burst rTMS on each of three days within an eight-day span. A single session = 600 pulses at 120% resting motor threshold (rMT), intermittent Theta Burst Stimulation (iTBS) triplets at 50 Hz for 2 seconds and repeated every 10 seconds for a total of 190 s to left dorsolateral prefrontal cortex. Total pulses = 14,400. To enable adherence and retention, the days do not need to be contiguous. Same day sessions will be separated by 10-15 minutes, but more accounting for participant comfort.
arm group label: High-dose accelerated rTMS
criteria: 
gender: All
minimum age: 65 Years
maximum age: 85 Years
healthy volunteers: No
last name: Andreana Benitez, PhD
role: Principal Investigator
affiliation: Medical University of South Carolina
last name: Lisa McTeague, PhD
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Medical University of South Carolina
investigator full name: Andreana Benitez
investigator title: Associate Professor
mesh term: Cognitive Dysfunction
sharing ipd: No
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