<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/NCT03240692</url>
  </required_header>
  <id_info>
    <org_study_id>33797</org_study_id>
    <nct_id>NCT03240692</nct_id>
  </id_info>
  <brief_title>Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression: OL Cohort</brief_title>
  <acronym>SAINT-TRD</acronym>
  <official_title>Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression (SAINT-TRD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Schatzberg, Alan, M.D.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial&#xD;
      magnetic stimulation device for treatment-resistant depression. In this open label study, all&#xD;
      participants will receive accelerated theta-burst stimulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy&#xD;
      for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for&#xD;
      40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for a 6 week treatment&#xD;
      course. This methodology has been successful for many people with treatment-resistant&#xD;
      depression. One of the limitations of this approach is the long duration of the treatment&#xD;
      course (approximately a 6 weeks per treatment course). Recently, researchers have&#xD;
      aggressively pursued modifying the treatment parameters to reduce treatment course time with&#xD;
      some preliminary success. This study intends to further modify the parameters to create a&#xD;
      more rapid form of the treatment. This study will also look at the change in neuroimaging&#xD;
      biomarkers associated with this treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Actual">March 3, 2020</completion_date>
  <primary_completion_date type="Actual">December 1, 2019</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>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month</measure>
    <time_frame>Pre-treatment and 1-month post treatment.</time_frame>
    <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment</time_frame>
    <description>A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in the Hamilton Rating Scale for Depression (HAM-6)</measure>
    <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment</time_frame>
    <description>A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in the Hamilton Rating Scale for Depression (HAM-17)</measure>
    <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment</time_frame>
    <description>A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Functional Connectivity to 1-month Post-treatment</measure>
    <time_frame>Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment</time_frame>
    <description>We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in the Beck Depression Inventory (BDI-II)</measure>
    <time_frame>Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.</time_frame>
    <description>A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)</measure>
    <time_frame>Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment</time_frame>
    <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline Functional Connectivity to Immediately Post-treatment</measure>
    <time_frame>Pre-treatment to immediately post treatment (on day 5).</time_frame>
    <description>Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus).&#xD;
T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>A Neuropsychological Test Battery Testing Cognitive Abilities</measure>
    <time_frame>Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment</time_frame>
    <description>The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">23</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>Accelerated theta burst treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive theta-burst TMS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Accelerated theta-burst stimulation treatment</intervention_name>
    <description>All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
    <arm_group_label>Accelerated theta burst treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female, 22 to 80 years of age.&#xD;
&#xD;
          -  Able to provide informed consent.&#xD;
&#xD;
          -  Diagnosed with Major Depressive Disorder (MDD) and currently experiencing a Major&#xD;
             Depressive Episode (MDE).&#xD;
&#xD;
          -  Participants may currently be on a stable and adequate dose of an antidepressant&#xD;
             therapy but the medication must remain stable throughout study enrollment.&#xD;
&#xD;
          -  Participants may also have a history of intolerance to antidepressant medications.&#xD;
             These patients with the intolerance history will not be required to be currently&#xD;
             taking an antidepressant medication.&#xD;
&#xD;
          -  Meet the threshold on the total HAMD17 score of &gt;/=20 at both screening and baseline&#xD;
             visits (Day -5/-14 and Day 0).&#xD;
&#xD;
          -  Meet the threshold on the total MADRS score of &gt;/=20 at both screening and baseline&#xD;
             visits (Day -5/-14 and Day 0).&#xD;
&#xD;
          -  Meet the threshold on the total BDI-II score of &gt;/=20 at both screening and baseline&#xD;
             visits (Day -5/-14 and Day 0).&#xD;
&#xD;
          -  In good general health, as ascertained by medical history.&#xD;
&#xD;
          -  If female, a status of non-childbearing potential or use of an acceptable form of&#xD;
             birth control.&#xD;
&#xD;
          -  Concurrent hypnotic therapy (e.g., with zolpidem, zaleplon, melatonin, or trazodone)&#xD;
             will be allowed if the therapy has been stable for at least 4 weeks prior to screening&#xD;
             and if it is expected to remain stable.&#xD;
&#xD;
          -  History of ECT intolerance is permitted.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female of childbearing potential who is not willing to use one of the specified forms&#xD;
             of birth control during the study.&#xD;
&#xD;
          -  Female that is pregnant or breastfeeding.&#xD;
&#xD;
          -  Total HAMD score of &lt; 20 at the screen or baseline visits.&#xD;
&#xD;
          -  Total MADRS score of &lt; 20 at the screen or baseline visits.&#xD;
&#xD;
          -  Total BDI-II score of &lt; 20 at the screen or baseline visits.&#xD;
&#xD;
          -  Current diagnosis of a Substance Use Disorder (Abuse or Dependence, as defined by&#xD;
             DSM-IV-TR), with the exception of nicotine dependence.&#xD;
&#xD;
          -  Current diagnosis of Axis I disorders other than Dysthymic Disorder, Generalized&#xD;
             Anxiety Disorder, Social Anxiety Disorder, Panic Disorder, Agoraphobia, or Specific&#xD;
             Phobia (unless one of these is comorbid and clinically unstable, and/or the focus of&#xD;
             the participant's treatment for the past six months or more).&#xD;
&#xD;
          -  History of schizophrenia or schizoaffective disorders, or any history of psychotic&#xD;
             symptoms in the current or previous depressive episodes.&#xD;
&#xD;
          -  Any Axis I or Axis II Disorder, which at screening is clinically predominant to their&#xD;
             MDD or has been predominant to their MDD at any time within six months prior to&#xD;
             screening.&#xD;
&#xD;
          -  Has a clinically significant abnormality on the screening examination that might&#xD;
             affect safety, study participation, or confound interpretation of study results.&#xD;
&#xD;
          -  Participation in any clinical trial with an investigational drug or device within the&#xD;
             past month or concurrent to study participation.&#xD;
&#xD;
          -  Any current or past history of any physical condition which in the investigator's&#xD;
             opinion might put the subject at risk or interfere with study results interpretation.&#xD;
&#xD;
          -  Positive screening on the urine test for drugs of abuse at screening: cocaine,&#xD;
             amphetamines, barbiturates, opiates.&#xD;
&#xD;
          -  Current (or chronic) use of opiates.&#xD;
&#xD;
          -  History of epilepsy.&#xD;
&#xD;
          -  History of shrapnel or metal in the head or skull.&#xD;
&#xD;
          -  History of cardiovascular disease or cardiac event.&#xD;
&#xD;
          -  History of OCD.&#xD;
&#xD;
          -  History of autism spectrum disorder.&#xD;
&#xD;
          -  History of rTMS exposure&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Nolan Williams, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nolan Williams, MD</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>George MS, Lisanby SH, Avery D, McDonald WM, Durkalski V, Pavlicova M, Anderson B, Nahas Z, Bulow P, Zarkowski P, Holtzheimer PE 3rd, Schwartz T, Sackeim HA. Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial. Arch Gen Psychiatry. 2010 May;67(5):507-16. doi: 10.1001/archgenpsychiatry.2010.46.</citation>
    <PMID>20439832</PMID>
  </reference>
  <reference>
    <citation>George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.</citation>
    <PMID>8547583</PMID>
  </reference>
  <reference>
    <citation>Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.</citation>
    <PMID>8684201</PMID>
  </reference>
  <reference>
    <citation>Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.</citation>
    <PMID>26850210</PMID>
  </reference>
  <reference>
    <citation>Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.</citation>
    <PMID>25281475</PMID>
  </reference>
  <reference>
    <citation>Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.</citation>
    <PMID>25450537</PMID>
  </reference>
  <reference>
    <citation>Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.</citation>
    <PMID>24411682</PMID>
  </reference>
  <reference>
    <citation>Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.</citation>
    <PMID>25430687</PMID>
  </reference>
  <reference>
    <citation>Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.</citation>
    <PMID>24833712</PMID>
  </reference>
  <reference>
    <citation>Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.</citation>
    <PMID>19862614</PMID>
  </reference>
  <reference>
    <citation>Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.</citation>
    <PMID>20734360</PMID>
  </reference>
  <reference>
    <citation>Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.</citation>
    <PMID>24060620</PMID>
  </reference>
  <reference>
    <citation>Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995 Oct;34(4):537-41. doi: 10.1002/mrm.1910340409.</citation>
    <PMID>8524021</PMID>
  </reference>
  <reference>
    <citation>Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. doi: 10.1073/pnas.0135058100. Epub 2002 Dec 27.</citation>
    <PMID>12506194</PMID>
  </reference>
  <reference>
    <citation>Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8. doi: 10.1073/pnas.0504136102. Epub 2005 Jun 23.</citation>
    <PMID>15976020</PMID>
  </reference>
  <reference>
    <citation>Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009 Jan;19(1):72-8. doi: 10.1093/cercor/bhn059. Epub 2008 Apr 9.</citation>
    <PMID>18403396</PMID>
  </reference>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>April 23, 2016</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <results_first_submitted>January 26, 2022</results_first_submitted>
  <results_first_submitted_qc>April 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">April 21, 2022</results_first_posted>
  <last_update_submitted>April 20, 2022</last_update_submitted>
  <last_update_submitted_qc>April 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Nolan R</investigator_full_name>
    <investigator_title>Assistant Professor of Psychiatry &amp; Behavioral Sciences, Director of the Brain Stimulation Laboratory at Stanford University School of Medicine</investigator_title>
  </responsible_party>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Treatment-Resistant Depression</keyword>
  <keyword>Transcranial Magnetic Stimulation (TMS)</keyword>
  <keyword>Theta-Burst Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>clintrials.gov</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03240692/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03240692/SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Accelerated Theta Burst Treatment</title>
          <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="23"/>
              </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="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Participants who completed the protocol are included in the analysis.</population>
      <group_list>
        <group group_id="B1">
          <title>Accelerated Theta Burst Treatment</title>
          <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</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="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="44.86" spread="17.21"/>
                  </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="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <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="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <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="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Montgomery Asberg Depression Rating Scale (MADRS) Score</title>
          <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.</description>
          <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="34.86" spread="5.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Columbia Suicide Severity Rating Scale (C-SSRS)</title>
          <description>A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.</description>
          <population>Participants who provided data are included in the analysis.</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="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1.42" spread="0.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Rating Scale for Depression (HAM-6)</title>
          <description>A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology.</description>
          <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="13.90" spread="2.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Hamilton Rating Scale for Depression (HAM-17)</title>
          <description>A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology.</description>
          <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="25.90" spread="4.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Beck Depression Inventory (BDI-II)</title>
          <description>A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology.</description>
          <population>Participants who provided data are included in the analysis.</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="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.78" spread="11.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month</title>
        <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.</description>
        <time_frame>Pre-treatment and 1-month post treatment.</time_frame>
        <population>Participants who completed the protocol are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month</title>
          <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.</description>
          <population>Participants who completed the protocol are included in the analysis.</population>
          <units>Percentage of change in 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="-67.07" spread="34.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
        <description>A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.</description>
        <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
          <description>A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>Percentage of change in 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="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-100" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4 weeks post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-100" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in the Hamilton Rating Scale for Depression (HAM-6)</title>
        <description>A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
        <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Hamilton Rating Scale for Depression (HAM-6)</title>
          <description>A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>Percentage of change in 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>
              <title>immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-81.96" spread="25.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-71.94" spread="37.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-65.54" spread="39.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-87.5" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in the Hamilton Rating Scale for Depression (HAM-17)</title>
        <description>A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
        <time_frame>Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Hamilton Rating Scale for Depression (HAM-17)</title>
          <description>A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>Percentage of change in 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>
              <title>immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-81.12" spread="23.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-74.58" spread="27.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-68.25" spread="32.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-88.89" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-93.52" spread="4.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Functional Connectivity to 1-month Post-treatment</title>
        <description>We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.</description>
        <time_frame>Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment</time_frame>
        <population>Data analysis was not possible due to missing data and poor image quality (unable to read)</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Functional Connectivity to 1-month Post-treatment</title>
          <description>We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.</description>
          <population>Data analysis was not possible due to missing data and poor image quality (unable to read)</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in the Beck Depression Inventory (BDI-II)</title>
        <description>A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
        <time_frame>Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Beck Depression Inventory (BDI-II)</title>
          <description>A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>Percentage of change in 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="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="15"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-84.89" spread="15.36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-65.32" spread="49.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-54.84" spread="46.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-90.74" spread="13.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-100" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)</title>
        <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
        <time_frame>Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)</title>
          <description>A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>Percentage of change in 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>
              <title>immediately post treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-85.06" spread="19.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-78.17" spread="25.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-67.07" spread="37.74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-96.30" spread="5.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline Functional Connectivity to Immediately Post-treatment</title>
        <description>Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus).&#xD;
T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.</description>
        <time_frame>Pre-treatment to immediately post treatment (on day 5).</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline Functional Connectivity to Immediately Post-treatment</title>
          <description>Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus).&#xD;
T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.</description>
          <population>Participants who provided data for the respective time point are included in the analysis</population>
          <units>T-score</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>sgACC-fDMN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.335"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sgACC-mDMN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sgACC-lDMN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>sgACC-rDMN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.660"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis of subgenual Anterior Cingulate Cortex (sgACC) and frontal Default Mode Network (fDMN) functional connectivity</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.036</p_value>
            <p_value_desc>False Discovery Corrected (FDR) p value. A p-value of ≤ 0.05 was considered to be statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis of subgenual Anterior Cingulate Cortex (sgACC) and medial Default Mode Network (mDMN) functional connectivity</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.008</p_value>
            <p_value_desc>False Discovery Corrected (FDR) p value. A p-value of ≤ 0.05 was considered to be statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis of subgenual Anterior Cingulate Cortex (sgACC) and left Default Mode Network (lDMN) functional connectivity.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.06</p_value>
            <p_value_desc>False Discovery Corrected (FDR) p value. A p-value of ≤ 0.05 was considered to be statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <groups_desc>Analysis of subgenual Anterior Cingulate Cortex (sgACC) and right Default Mode Network (rDMN) functional connectivity.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.017</p_value>
            <p_value_desc>False Discovery Corrected (FDR) p value. A p-value of ≤ 0.05 was considered to be statistically significant.</p_value_desc>
            <method>t-test, 2 sided</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>A Neuropsychological Test Battery Testing Cognitive Abilities</title>
        <description>The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.</description>
        <time_frame>Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment</time_frame>
        <population>Participants who provided data for the respective time point are included in the analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Accelerated Theta Burst Treatment</title>
            <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</description>
          </group>
        </group_list>
        <measure>
          <title>A Neuropsychological Test Battery Testing Cognitive Abilities</title>
          <description>The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.</description>
          <population>Participants who provided data for the respective time point are included in the analysis.</population>
          <units>score 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="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>HVLT-DR_Pre-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="16"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.81" spread="6.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HVLT-DR_ immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.18" spread="9.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HVLT-DR_Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.77" spread="10.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BVMT-DR_Pre-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.06" spread="9.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BVMT-DR_ immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.35" spread="8.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>BVMT-DR_Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="56.23" spread="11.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DKEFS_Pre-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17.35" spread="4.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DKEFS_ immediately post-treatment</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.06" spread="4.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DKEFS_Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="13"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.15" spread="3.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 26 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Accelerated Theta Burst Treatment</title>
          <description>All participants will receive theta-burst TMS.&#xD;
Accelerated theta-burst stimulation treatment: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).&#xD;
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.</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="23"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="23"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Dr. Nolan Williams</name_or_title>
      <organization>Stanford University</organization>
      <phone>650-800-6920</phone>
      <email>nolanw@stanford.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/NCT03240692
org study id: 33797
nct id: NCT03240692
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
This study evaluates an accelerated schedule of theta-burst stimulation using a transcranial
      magnetic stimulation device for treatment-resistant depression. In this open label study, all
      participants will receive accelerated theta-burst stimulation.
Repetitive transcranial magnetic stimulation (rTMS) is an established technology as therapy
      for treatment-resistant depression. The approved method for treatment is 10Hz stimulation for
      40 minutes over the left dorsolateral prefrontal cortex (L-DLPFC) for a 6 week treatment
      course. This methodology has been successful for many people with treatment-resistant
      depression. One of the limitations of this approach is the long duration of the treatment
      course (approximately a 6 weeks per treatment course). Recently, researchers have
      aggressively pursued modifying the treatment parameters to reduce treatment course time with
      some preliminary success. This study intends to further modify the parameters to create a
      more rapid form of the treatment. This study will also look at the change in neuroimaging
      biomarkers associated with this treatment.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS) Score From Pre-treatment to 1-month
time frame: Pre-treatment and 1-month post treatment.
description: A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology.
measure: Percent Change in the Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Pre-treatment to immediately post-treatment (on day 5) and 4 weeks post-treatment
description: A suicidal ideation rating scale created by researchers at Columbia University. The score was calculated by summing the answers to 5 questions. Score range - 0 to 5. Higher score indicate higher suicidal ideation.
measure: Percent Change in the Hamilton Rating Scale for Depression (HAM-6)
time frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks,4 weeks and 6 weeks post-treatment
description: A 6 item questionnaire used to score the severity of depression. Scale range - 0 to 22 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
measure: Percent Change in the Hamilton Rating Scale for Depression (HAM-17)
time frame: Pre-treatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post-treatment
description: A provider administered questionnaire used to assess remission and recovery from depression. Scale range - 0 to 52 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
measure: Change From Baseline Functional Connectivity to 1-month Post-treatment
time frame: Pre-treatment, immediately post-treatment (on day 5), 1-month post-treatment
description: We will assess change in resting state fMRI functional connectivity of the subcallosal cingulate to the default mode network and within the default mode network.
measure: Percent Change in the Beck Depression Inventory (BDI-II)
time frame: Pretreatment to immediately post-treatment (on day 5) and 2 weeks, 4 weeks, 6 weeks and 8 weeks post treatment.
description: A 21 item Self-report measure of depressive symptoms. Scale range - 0 to 63 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
measure: Percent Change in the Montgomery Asberg Depression Rating Scale (MADRS)
time frame: Pre-treatment to immediately post treatment (on day 5) and 2 weeks, 4 weeks and 8 weeks post-treatment
description: A ten item diagnostic questionnaire used to measure the severity of depressive symptoms in patients with mood disorders. Scale range - 0 to 60 with higher score indicative of greater depressive symptomology. Additional collection time points were pre-specified; only those time points for which data were collected are reported.
measure: Change From Baseline Functional Connectivity to Immediately Post-treatment
time frame: Pre-treatment to immediately post treatment (on day 5).
description: Within subject changes in resting state functional connectivity of subgenual anterior cingulate cortex (sgACC) to default mode network (DMN). frontal (f)DMN (medial prefrontal cortex), median (m)DMN (posterior cingulate cortex and precuneus), left (l)DMN (left angular gyrus), right (r)DMN (right angular gyrus).
T-statistic (T-score): ratio of departure of estimated value from its hypothesized value to its standard error used in a t-test to determine whether to support or reject the null hypothesis. A T-score of ≥ 2.11 or ≤ -2.11 would be considered a statistically significant change if the accompanying p-value (subject to false discovery rate correction of multiple comparisons) was ≤ 0.05. Positive T-score = increased connectivity, negative T-score = decreased connectivity. No established reference range or clinically meaningful threshold exists for this patient population. Higher connectivity between all DMN nodes to sgACC has been found in depressed vs healthy population.
measure: A Neuropsychological Test Battery Testing Cognitive Abilities
time frame: Pre-treatment, immediately post-treatment (on day 5) and 4 weeks post-treatment
description: The Hopkins Verbal Learning Test - Revised (HVLT-DR). Score range 0 to 72, higher score indicates better verbal learning. The Brief Visuospatial Memory Test - Revised (BVMT-DR). Score range 0 to 84, higher score indicates better visuospatial memory. Digit Span test and various tests from the Delis Kaplan Executive Function System (DKEFS) will be used to assess possible cognitive side-effects. Score range 0-36, higher score indicates better executive functions.
arm group label: Accelerated theta burst treatment
arm group type: Experimental
description: All participants will receive theta-burst TMS.
intervention type: Device
intervention name: Accelerated theta-burst stimulation treatment
description: All participants will receive intermittent theta-burst stimulation (iTBS) to the left dorsal lateral prefrontal cortex (L-DLPFC). The L-DLPFC will be targeted utilizing the Localite neuronavigation system. Stimulation intensity will be standardized at 90% of resting motor threshold (adjusted for cortical depth).
Stimulation will be delivered to L-DLPFC using the Magventure Magpro X100 and/or the NextStim TMS system.
arm group label: Accelerated theta burst treatment
criteria: 
gender: All
minimum age: 22 Years
maximum age: 80 Years
healthy volunteers: No
last name: Nolan Williams, MD
role: Principal Investigator
affiliation: Stanford University
facility: 
country: United States
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PMID: 20439832
citation: George MS, Wassermann EM, Williams WA, Callahan A, Ketter TA, Basser P, Hallett M, Post RM. Daily repetitive transcranial magnetic stimulation (rTMS) improves mood in depression. Neuroreport. 1995 Oct 2;6(14):1853-6. doi: 10.1097/00001756-199510020-00008.
PMID: 8547583
citation: Pascual-Leone A, Rubio B, Pallardo F, Catala MD. Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet. 1996 Jul 27;348(9022):233-7. doi: 10.1016/s0140-6736(96)01219-6.
PMID: 8684201
citation: Chung SW, Hill AT, Rogasch NC, Hoy KE, Fitzgerald PB. Use of theta-burst stimulation in changing excitability of motor cortex: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2016 Apr;63:43-64. doi: 10.1016/j.neubiorev.2016.01.008. Epub 2016 Feb 3.
PMID: 26850210
citation: Jelic MB, Milanovic SD, Filipovic SR. Differential effects of facilitatory and inhibitory theta burst stimulation of the primary motor cortex on motor learning. Clin Neurophysiol. 2015 May;126(5):1016-23. doi: 10.1016/j.clinph.2014.09.003. Epub 2014 Sep 16.
PMID: 25281475
citation: Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety. 2015 Mar;32(3):182-92. doi: 10.1002/da.22335. Epub 2014 Nov 28.
PMID: 25450537
citation: Plewnia C, Pasqualetti P, Grosse S, Schlipf S, Wasserka B, Zwissler B, Fallgatter A. Treatment of major depression with bilateral theta burst stimulation: a randomized controlled pilot trial. J Affect Disord. 2014 Mar;156:219-23. doi: 10.1016/j.jad.2013.12.025. Epub 2013 Dec 28.
PMID: 24411682
citation: Prasser J, Schecklmann M, Poeppl TB, Frank E, Kreuzer PM, Hajak G, Rupprecht R, Landgrebe M, Langguth B. Bilateral prefrontal rTMS and theta burst TMS as an add-on treatment for depression: a randomized placebo controlled trial. World J Biol Psychiatry. 2015 Jan;16(1):57-65. doi: 10.3109/15622975.2014.964768. Epub 2014 Nov 28.
PMID: 25430687
citation: Daskalakis ZJ. Theta-burst transcranial magnetic stimulation in depression: when less may be more. Brain. 2014 Jul;137(Pt 7):1860-2. doi: 10.1093/brain/awu123. Epub 2014 May 15. No abstract available.
PMID: 24833712
citation: Thut G, Pascual-Leone A. A review of combined TMS-EEG studies to characterize lasting effects of repetitive TMS and assess their usefulness in cognitive and clinical neuroscience. Brain Topogr. 2010 Jan;22(4):219-32. doi: 10.1007/s10548-009-0115-4. Epub 2009 Oct 28.
PMID: 19862614
citation: Holtzheimer PE 3rd, McDonald WM, Mufti M, Kelley ME, Quinn S, Corso G, Epstein CM. Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depress Anxiety. 2010 Oct;27(10):960-3. doi: 10.1002/da.20731.
PMID: 20734360
citation: Fung PK, Robinson PA. Neural field theory of synaptic metaplasticity with applications to theta burst stimulation. J Theor Biol. 2014 Jan 7;340:164-76. doi: 10.1016/j.jtbi.2013.09.021. Epub 2013 Sep 21.
PMID: 24060620
citation: Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med. 1995 Oct;34(4):537-41. doi: 10.1002/mrm.1910340409.
PMID: 8524021
citation: Greicius MD, Krasnow B, Reiss AL, Menon V. Functional connectivity in the resting brain: a network analysis of the default mode hypothesis. Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):253-8. doi: 10.1073/pnas.0135058100. Epub 2002 Dec 27.
PMID: 12506194
citation: Fox MD, Snyder AZ, Vincent JL, Corbetta M, Van Essen DC, Raichle ME. The human brain is intrinsically organized into dynamic, anticorrelated functional networks. Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9673-8. doi: 10.1073/pnas.0504136102. Epub 2005 Jun 23.
PMID: 15976020
citation: Greicius MD, Supekar K, Menon V, Dougherty RF. Resting-state functional connectivity reflects structural connectivity in the default mode network. Cereb Cortex. 2009 Jan;19(1):72-8. doi: 10.1093/cercor/bhn059. Epub 2008 Apr 9.
PMID: 18403396
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Nolan R
investigator title: Assistant Professor of Psychiatry & Behavioral Sciences, Director of the Brain Stimulation Laboratory at Stanford University School of Medicine
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
sharing ipd: No
ipd description: clintrials.gov
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