<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/NCT02974296</url>
  </required_header>
  <id_info>
    <org_study_id>7159</org_study_id>
    <nct_id>NCT02974296</nct_id>
  </id_info>
  <brief_title>Neuroimaging in Patients Undergoing TMS for Depression</brief_title>
  <acronym>NIPUTFD</acronym>
  <official_title>Neuroimaging in Patients Undergoing TMS for Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of this project is to guide rTMS using functional magnetic resonance imaging (fMRI)&#xD;
      in individuals with depression who did not respond to standard TMS treatment to evaluate&#xD;
      whether targeted TMS using individualized functional MRI scans produce outcome superior to&#xD;
      that of conventional approaches. The study team also plans to scan patients with Major&#xD;
      Depression Disorder (MDD) patients prescribed to receive standard TMS for the first time&#xD;
      before and after which they will have resting-state Functional Magnetic Resonance Imaging&#xD;
      (rs-FMRI) scan in order to see if we can predict their responsiveness based on the functional&#xD;
      connectivity maps.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Significance: There are few therapeutic options for individuals with treatment resistant&#xD;
      depression (TRD). One recently developed approach is rTMS over left dorsolateral prefrontal&#xD;
      cortex. Recent studies have demonstrated overall antidepressant benefit of rTMS in patients&#xD;
      who fail to respond to a trial of antidepressant medication (1, 2, 3). Nevertheless, for many&#xD;
      patients the response is incomplete, suggesting the need for further optimization. One&#xD;
      potential cause of heterogeneous response might relate to individual differences in brain&#xD;
      anatomy and connectivity patterns. At present, the rTMS stimulation site across subjects is&#xD;
      based upon fixed location relative to motor cortex. Potentially, however, the approach could&#xD;
      be optimized by stimulating based upon individual brain functional connectivity pattern. The&#xD;
      present project will collect pre- and post-treatment brain functional connectivity measures&#xD;
      in a group of patients who will be receiving independent clinical rTMS for resistant&#xD;
      depression, a connectivity-based targeting approach will be applied at the single-subject&#xD;
      level to individualize therapy in those patients who do not respond to standard approaches.&#xD;
&#xD;
      Patients will be divided in 2 groups. Group 1 (N=30) will be depressed patients undergoing&#xD;
      standard TMS for the first time. Group 2 (N=30) constitutes those who have previously&#xD;
      demonstrated that they do not respond to standard TMS. MDD patients prescribed to receive&#xD;
      standard TMS for the first time (group 1) will have resting-state FMRI in order to see if&#xD;
      their responsiveness based on the functional connectivity maps can be predicted.&#xD;
      Non-responders to standard TMS approaches (Group 2) will be randomized (3:2) to either&#xD;
      receive targeted (N=18) or standard (N=12) repetitive TMS (rTMS) treatments. A&#xD;
      connectivity-based targeting strategy will be used on patients undergoing targeted rTMS to&#xD;
      optimize target for focal brain stimulation. Raters and patients in group 2 will be kept&#xD;
      blinded to the treatment assignment. All patients referred from the ongoing treatment study&#xD;
      will be assessed by 3 tesla brain MRI, Magnetic Resonance Spectroscopy (MRS) and Cerebral&#xD;
      Blood Flow/Volume (CBF/CBV) procedures at baseline and immediately following the final&#xD;
      treatment.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 30, 2017</start_date>
  <completion_date type="Actual">August 20, 2019</completion_date>
  <primary_completion_date type="Actual">August 20, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Functional Connectivity Measured by Resting MRI</measure>
    <time_frame>Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments</time_frame>
    <description>Change from Baseline in Resting MRI Correlation Coefficients Between Left Dorsolateral Prefrontal Cortex and Subgenual Anterior Cingulate Change in Resting MRI is defined as post-pre</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (17-item HDRS)</measure>
    <time_frame>Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments</time_frame>
    <description>Patients will be classified as responders to TMS with at least 50% decrease in HDRS scores from baseline. Patients will be classified as non-responders to TMS with less than 50% decrease in HDRS scores from baseline.&#xD;
Change in HDRS-17 scores is defined as: [pre-post)/pre]x100 HDRS-17 scores range: 0-61&#xD;
Levels of depression based on HDRS-17 scores:&#xD;
Not depressed: 0-7 Mild (subthreshold): 8-13 Moderate (mild): 14-18 Severe (moderate): 19-22 Very severe (severe): &gt;23</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Treatment Resistant Depression</condition>
  <arm_group>
    <arm_group_label>new target TMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>new target transcranial magnetic stimulation guided by MRI</description>
  </arm_group>
  <arm_group>
    <arm_group_label>standard TMS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>standard transcranial magnetic stimulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>transcranial magnetic stimulation</intervention_name>
    <description>non invasive brain stimulation approach</description>
    <arm_group_label>new target TMS</arm_group_label>
    <arm_group_label>standard TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          1. Male or female outpatients, 18 to 60 years of age.&#xD;
&#xD;
          2. Primary diagnosis of Major Depressive Disorder as confirmed by the Structured Clinical&#xD;
             Interview for Diagnostic and Statistical Manual (DSM-IV-TR) Disorders (SCID-IV-TR).&#xD;
&#xD;
          3. Duration of the index episode of at least 1 month.&#xD;
&#xD;
          4. MDD symptoms, defined as a total HDRS-17 score ≥ 18 despite treatment with an adequate&#xD;
             trial of a serotonin reuptake inhibitor (SRI).&#xD;
&#xD;
          5. Individuals who cannot tolerate medications.&#xD;
&#xD;
          6. Patients currently on medication must be at the same stable dose(s) for 1 month prior&#xD;
             to enrollment and be willing to continue at the same dose(s) through the duration of&#xD;
             the study.&#xD;
&#xD;
          7. Capable and willing to provide informed consent.&#xD;
&#xD;
          8. Signed HIPAA authorization.&#xD;
&#xD;
          9. Right-handed.&#xD;
&#xD;
         10. Willingness to undergo research fMRI scan (3T).&#xD;
&#xD;
         11. Willingness to undergo randomization to either treatment arm.&#xD;
&#xD;
        General Exclusion Criteria:&#xD;
&#xD;
          1. Investigators, and their immediate families (defined as a spouse, parent, child or&#xD;
             sibling, whether by birth or legal adoption).&#xD;
&#xD;
          2. Individuals diagnosed by the investigators with the following conditions: Bipolar&#xD;
             Disorder (lifetime), any Psychotic Disorder (lifetime), history of substance abuse or&#xD;
             dependence within the past year (except nicotine and caffeine).&#xD;
&#xD;
          3. Behavior, which in the judgment of the investigator may hinder the patient in&#xD;
             completing the procedures required by the study protocol.&#xD;
&#xD;
          4. Individuals with a clinically defined neurological disorder including, but not limited&#xD;
             to: tics, space occupying brain lesion; any history of seizures except those&#xD;
             therapeutically induced by electroconvulsive therapy (ECT); history of cerebrovascular&#xD;
             accident; history of fainting; transient ischemic attack within two years; cerebral&#xD;
             aneurysm, Dementia; Parkinson's Disease; Huntington chorea; Multiple Sclerosis.&#xD;
&#xD;
          5. Increased risk of seizure for any reason, including prior diagnosis of increased&#xD;
             intracranial pressure (such as after large infarctions or trauma), or history of&#xD;
             significant head trauma with loss of consciousness for ≥ 5 minutes.&#xD;
&#xD;
          6. Use of any investigational drug within 12 weeks of the randomization visit.&#xD;
&#xD;
          7. Significant acute suicide risk, defined as follow: suicide attempt within the previous&#xD;
             6 months that required medical treatment; or ≥ 2 suicide attempts in the past 12&#xD;
             months; or in the investigator's opinion, has significant risk for suicide based on&#xD;
             the current state or recent history.&#xD;
&#xD;
          8. Cardiac pacemakers, implanted medication pumps, intracardiac lines, or acute, unstable&#xD;
             cardiac disease.&#xD;
&#xD;
          9. Intracranial implants (e.g. aneurysms clips, shunts, stimulators, cochlear implants,&#xD;
             or electrodes) or any other metal object within or near the head, excluding the mouth,&#xD;
             that cannot be safely removed.&#xD;
&#xD;
         10. Current illicit drug use (cannabinoid, phencyclidine, amphetamines, barbiturates,&#xD;
             cocaine, methadone, and opiates), defined as drug use during the 6 months before&#xD;
             screening.&#xD;
&#xD;
         11. Known or suspected pregnancy. Urine pregnancy test Women who are breast-feeding.&#xD;
&#xD;
         12. Women of childbearing potential not using a medically accepted form of contraception&#xD;
             when engaging in sexual intercourse.&#xD;
&#xD;
         13. Medicinal patch, unless removed prior to the magnetic resonance (MR) scan.&#xD;
&#xD;
         14. MDD patients with very severe depression, defined as a total HDRS-17 score ≥ 23, will&#xD;
             be excluded and referred to immediate treatment.&#xD;
&#xD;
         15. Risks related to seizures, such as substance abuse or sleep disruptions/insomnia.&#xD;
&#xD;
        SpecificExclusion criteria (group 1):&#xD;
&#xD;
        History of treatment with rTMS therapy for any disorder.&#xD;
&#xD;
        Specific Inclusion criteria (group 2):&#xD;
&#xD;
        History of non-response to rTMS in this depressive episode.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel C. Javitt, MD Ph.D</last_name>
    <role>Study Director</role>
    <affiliation>New York State Psychiatric Institute &amp; Columbia University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Moreno-Ortega M, Kangarlu A, Lee S, Perera T, Kangarlu J, Palomo T, Glasser MF, Javitt DC. Parcel-guided rTMS for depression. Transl Psychiatry. 2020 Aug 12;10(1):283. doi: 10.1038/s41398-020-00970-8.</citation>
    <PMID>32788580</PMID>
  </reference>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>November 18, 2016</study_first_submitted>
  <study_first_submitted_qc>November 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 28, 2016</study_first_posted>
  <results_first_submitted>September 9, 2020</results_first_submitted>
  <results_first_submitted_qc>October 1, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 23, 2020</results_first_posted>
  <last_update_submitted>October 1, 2020</last_update_submitted>
  <last_update_submitted_qc>October 1, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Marta Moreno Ortega, PHD</investigator_full_name>
    <investigator_title>Associate Research Scientist</investigator_title>
  </responsible_party>
  <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>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT02974296/Prot_ICF_002.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>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT02974296/SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>New Target TMS</title>
          <description>new target transcranial magnetic stimulation guided by MRI&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
        </group>
        <group group_id="P2">
          <title>Standard TMS</title>
          <description>standard transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="23"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="22"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>New Target TMS</title>
          <description>new target transcranial magnetic stimulation guided by MRI&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
        </group>
        <group group_id="B2">
          <title>Standard TMS</title>
          <description>standard transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="22"/>
            <count group_id="B3" value="32"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.70" spread="16.028"/>
                    <measurement group_id="B2" value="41.50" spread="15.152"/>
                    <measurement group_id="B3" value="40.21" spread="15.275"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="22"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Functional Connectivity Measured by Resting MRI</title>
        <description>Change from Baseline in Resting MRI Correlation Coefficients Between Left Dorsolateral Prefrontal Cortex and Subgenual Anterior Cingulate Change in Resting MRI is defined as post-pre</description>
        <time_frame>Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments</time_frame>
        <group_list>
          <group group_id="O1">
            <title>New Target TMS</title>
            <description>new target transcranial magnetic stimulation guided by MRI&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
          </group>
          <group group_id="O2">
            <title>Standard TMS</title>
            <description>standard transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Functional Connectivity Measured by Resting MRI</title>
          <description>Change from Baseline in Resting MRI Correlation Coefficients Between Left Dorsolateral Prefrontal Cortex and Subgenual Anterior Cingulate Change in Resting MRI is defined as post-pre</description>
          <units>correlation coefficients</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.103399365" spread="0.161565183"/>
                    <measurement group_id="O2" value="-0.7637409" spread="0.106948404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (17-item HDRS)</title>
        <description>Patients will be classified as responders to TMS with at least 50% decrease in HDRS scores from baseline. Patients will be classified as non-responders to TMS with less than 50% decrease in HDRS scores from baseline.&#xD;
Change in HDRS-17 scores is defined as: [pre-post)/pre]x100 HDRS-17 scores range: 0-61&#xD;
Levels of depression based on HDRS-17 scores:&#xD;
Not depressed: 0-7 Mild (subthreshold): 8-13 Moderate (mild): 14-18 Severe (moderate): 19-22 Very severe (severe): &gt;23</description>
        <time_frame>Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments</time_frame>
        <group_list>
          <group group_id="O1">
            <title>New Target TMS</title>
            <description>new target transcranial magnetic stimulation guided by MRI&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
          </group>
          <group group_id="O2">
            <title>Standard TMS</title>
            <description>standard transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (17-item HDRS)</title>
          <description>Patients will be classified as responders to TMS with at least 50% decrease in HDRS scores from baseline. Patients will be classified as non-responders to TMS with less than 50% decrease in HDRS scores from baseline.&#xD;
Change in HDRS-17 scores is defined as: [pre-post)/pre]x100 HDRS-17 scores range: 0-61&#xD;
Levels of depression based on HDRS-17 scores:&#xD;
Not depressed: 0-7 Mild (subthreshold): 8-13 Moderate (mild): 14-18 Severe (moderate): 19-22 Very severe (severe): &gt;23</description>
          <units>percentage change in HDRS scores</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64.9440" spread="15.16426"/>
                    <measurement group_id="O2" value="27.7345" spread="27.48549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>6 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>New Target TMS</title>
          <description>new target transcranial magnetic stimulation guided by MRI&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</description>
        </group>
        <group group_id="E2">
          <title>Standard TMS</title>
          <description>standard transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: non invasive brain stimulation approach</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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </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. Marta Moreno-Ortega</name_or_title>
      <organization>Columbia University</organization>
      <phone>9142187311</phone>
      <email>mm4355@cumc.columbia.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/NCT02974296
org study id: 7159
nct id: NCT02974296
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
The goal of this project is to guide rTMS using functional magnetic resonance imaging (fMRI)
      in individuals with depression who did not respond to standard TMS treatment to evaluate
      whether targeted TMS using individualized functional MRI scans produce outcome superior to
      that of conventional approaches. The study team also plans to scan patients with Major
      Depression Disorder (MDD) patients prescribed to receive standard TMS for the first time
      before and after which they will have resting-state Functional Magnetic Resonance Imaging
      (rs-FMRI) scan in order to see if we can predict their responsiveness based on the functional
      connectivity maps.
Significance: There are few therapeutic options for individuals with treatment resistant
      depression (TRD). One recently developed approach is rTMS over left dorsolateral prefrontal
      cortex. Recent studies have demonstrated overall antidepressant benefit of rTMS in patients
      who fail to respond to a trial of antidepressant medication (1, 2, 3). Nevertheless, for many
      patients the response is incomplete, suggesting the need for further optimization. One
      potential cause of heterogeneous response might relate to individual differences in brain
      anatomy and connectivity patterns. At present, the rTMS stimulation site across subjects is
      based upon fixed location relative to motor cortex. Potentially, however, the approach could
      be optimized by stimulating based upon individual brain functional connectivity pattern. The
      present project will collect pre- and post-treatment brain functional connectivity measures
      in a group of patients who will be receiving independent clinical rTMS for resistant
      depression, a connectivity-based targeting approach will be applied at the single-subject
      level to individualize therapy in those patients who do not respond to standard approaches.

      Patients will be divided in 2 groups. Group 1 (N=30) will be depressed patients undergoing
      standard TMS for the first time. Group 2 (N=30) constitutes those who have previously
      demonstrated that they do not respond to standard TMS. MDD patients prescribed to receive
      standard TMS for the first time (group 1) will have resting-state FMRI in order to see if
      their responsiveness based on the functional connectivity maps can be predicted.
      Non-responders to standard TMS approaches (Group 2) will be randomized (3:2) to either
      receive targeted (N=18) or standard (N=12) repetitive TMS (rTMS) treatments. A
      connectivity-based targeting strategy will be used on patients undergoing targeted rTMS to
      optimize target for focal brain stimulation. Raters and patients in group 2 will be kept
      blinded to the treatment assignment. All patients referred from the ongoing treatment study
      will be assessed by 3 tesla brain MRI, Magnetic Resonance Spectroscopy (MRS) and Cerebral
      Blood Flow/Volume (CBF/CBV) procedures at baseline and immediately following the final
      treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in Functional Connectivity Measured by Resting MRI
time frame: Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments
description: Change from Baseline in Resting MRI Correlation Coefficients Between Left Dorsolateral Prefrontal Cortex and Subgenual Anterior Cingulate Change in Resting MRI is defined as post-pre
measure: Change in Depressive Symptoms Measured by the Hamilton Depression Rating Scale (17-item HDRS)
time frame: Week 1 prior to first TMS treatment and week 36 after completion of TMS treatments
description: Patients will be classified as responders to TMS with at least 50% decrease in HDRS scores from baseline. Patients will be classified as non-responders to TMS with less than 50% decrease in HDRS scores from baseline.
Change in HDRS-17 scores is defined as: [pre-post)/pre]x100 HDRS-17 scores range: 0-61
Levels of depression based on HDRS-17 scores:
Not depressed: 0-7 Mild (subthreshold): 8-13 Moderate (mild): 14-18 Severe (moderate): 19-22 Very severe (severe): >23
arm group label: new target TMS
arm group type: Experimental
description: new target transcranial magnetic stimulation guided by MRI
arm group label: standard TMS
arm group type: Active Comparator
description: standard transcranial magnetic stimulation
intervention type: Device
intervention name: transcranial magnetic stimulation
description: non invasive brain stimulation approach
arm group label: new target TMS
arm group label: standard TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Daniel C. Javitt, MD Ph.D
role: Study Director
affiliation: New York State Psychiatric Institute & Columbia University
facility: 
country: United States
citation: Moreno-Ortega M, Kangarlu A, Lee S, Perera T, Kangarlu J, Palomo T, Glasser MF, Javitt DC. Parcel-guided rTMS for depression. Transl Psychiatry. 2020 Aug 12;10(1):283. doi: 10.1038/s41398-020-00970-8.
PMID: 32788580
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Marta Moreno Ortega, PHD
investigator title: Associate Research Scientist
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 