<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/NCT03037983</url>
  </required_header>
  <id_info>
    <org_study_id>D2382-P</org_study_id>
    <secondary_id>12246865</secondary_id>
    <secondary_id>38101</secondary_id>
    <nct_id>NCT03037983</nct_id>
  </id_info>
  <brief_title>Improving Neurocognitive Deficits and Function in Schizophrenia With Transcranial Magnetic Stimulation</brief_title>
  <official_title>Improving Neurocognitive Deficits and Function in Schizophrenia With Transcranial Magnetic Stimulation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Office of Research and Development</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>
      The purpose of this study is to determine whether repetitive transcranial magnetic&#xD;
      stimulation (rTMS) is effective in remediating cognitive deficits while also improving&#xD;
      functionality in Veterans with schizophrenia.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      High-frequency, repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral&#xD;
      prefrontal cortex (DLPFC), the dysfunctional brain region most implicated in cognitive&#xD;
      deficits in schizophrenia, has recently been shown to improve cognition in non-Veteran&#xD;
      samples with schizophrenia. The investigators' goal is to confirm the efficacy of this&#xD;
      treatment modality to remediate cognitive deficits and improve functionality in Veterans with&#xD;
      schizophrenia, as well as to gain a better understanding of the neural mechanisms responsible&#xD;
      for cognitive deficits and their remediation. The investigators propose conducting a&#xD;
      small-scale study to generate pilot data supporting the feasibility of conducting rTMS with&#xD;
      Veterans and the effectiveness of rTMS in this population. In addition, the investigators&#xD;
      will conduct neurophysiologic experiments to test whether certain neural maker of abnormal&#xD;
      brain function improves with rTMS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">July 1, 2019</completion_date>
  <primary_completion_date type="Actual">July 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>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Supportive Care</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Working Memory Function</measure>
    <time_frame>before treatment and after 6-week treatment</time_frame>
    <description>Changes in scores for working memory performance accuracy will serve as dependent measure for testing the hypothesis that rTMS improves working memory. Working memory performance was assessed using a non-standardized task developed in house, which is basically a Sterberg style delayed response task in which memoranda are displayed and are to be remembered across a short delay period. The hypothesis will be supported if the investigators find greater working memory difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scores will be reported as a change in percent accuracy during this working memory task, where higher percent accuracy is better and scores range from -100% to 100%.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Neurophysiologic Function</measure>
    <time_frame>before treatment and after 6-week treatment</time_frame>
    <description>Gamma oscillation is viewed as a measure of neurophysiologic function. The investigators will be conducting task-evoked electroencephalography (EEG) to measure gamma oscillation before and after rTMS. It is predicted that the intervention will improve gamma oscillations.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Level of Everyday Functioning</measure>
    <time_frame>before treatment and after 6-week treatment</time_frame>
    <description>Changes in Global Functioning Scale scores (GF) will serve as dependent measure for testing the hypothesis that rTMS improves functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05.&#xD;
Scale's values range from a minimum score of 1 to a maximum score of 10, with a higher score means better functioning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in General Cognitive Ability</measure>
    <time_frame>before treatment and after 6-week treatment</time_frame>
    <description>Changes in Brief Assessment of Cognition (BACS) score will serve as a dependent measure for testing the hypothesis that rTMS improves cognitive functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Data will be reported as change in Z-score on the scale, where a higher value means a better outcome, with scores ranging from -3 to 3.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">9</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <arm_group>
    <arm_group_label>Active rTMS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects will receive actual rTMS treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham rTMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive transcranial magnetic stimulation</intervention_name>
    <description>rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
    <arm_group_label>Active rTMS</arm_group_label>
    <other_name>rTMS</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham</intervention_name>
    <description>Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
    <arm_group_label>Sham rTMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  SCID (Structured Clinical Interview for DSM Disorders) confirmed diagnosis of&#xD;
             Schizophrenia or Schizoaffective Disorder&#xD;
&#xD;
          -  Stable medication regimen (no change in dose or agents within the 2 weeks prior to&#xD;
             study entry and throughout the duration of the study)&#xD;
&#xD;
          -  Stable social environment and housing to enable regular attendance at clinic visits&#xD;
&#xD;
          -  Ability to undergo cognitive testing, EEG scans and rTMS&#xD;
&#xD;
          -  IQ (intelligence quotient) &gt; 80 (WASI full scale score)&#xD;
&#xD;
          -  In general good medical health&#xD;
&#xD;
          -  Is in treatment with a psychiatrist and/or primary care physician within the VHA&#xD;
             (Veteran's Health Administration) system&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant or lactating female&#xD;
&#xD;
          -  History of prior adverse reaction to TMS&#xD;
&#xD;
          -  On medications known to significantly lower seizure threshold, e.g.:&#xD;
&#xD;
               -  clozapine&#xD;
&#xD;
               -  chlorpromazine&#xD;
&#xD;
               -  clomipramine&#xD;
&#xD;
          -  History of seizures or conditions known to substantially increase risk for seizures&#xD;
&#xD;
          -  Implants or medical devices incompatible with TMS&#xD;
&#xD;
          -  Acute or unstable chronic illness that would affect participation or compliance with&#xD;
             study procedures, e.g.:&#xD;
&#xD;
               -  unstable angina&#xD;
&#xD;
          -  Substance abuse/dependence (not including caffeine or nicotine) within one-month&#xD;
             period prior to study entry or during study participation&#xD;
&#xD;
          -  Unstable psychiatric symptoms that precludes consistent participation in the study,&#xD;
             e.g.:&#xD;
&#xD;
               -  active current suicidal intent or plan&#xD;
&#xD;
               -  severe psychosis&#xD;
&#xD;
          -  History of loss of consciousness greater than 15 minutes due to head injury.&#xD;
&#xD;
          -  Participation in another concurrent clinical trial&#xD;
&#xD;
          -  Patients with prior exposure to rTMS&#xD;
&#xD;
          -  Have a mass lesion, cerebral infarct or other active central nervous system disease,&#xD;
             or history of traumatic brain injury&#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>Jong H. Yoon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Palo Alto Health Care System, Palo Alto, CA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>VA Palo Alto Health Care System, Palo Alto, CA</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304-1290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>January 27, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <results_first_submitted>June 4, 2020</results_first_submitted>
  <results_first_submitted_qc>August 14, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 17, 2020</results_first_posted>
  <last_update_submitted>August 14, 2020</last_update_submitted>
  <last_update_submitted_qc>August 14, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 17, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Transcranial magnetic stimulation</keyword>
  <keyword>Electroencephalography</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 18, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/83/NCT03037983/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Of the approached potential participants, many were unable to participate due to difficulties with the amount of time required to participate in the study, or a change in interest.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Active</title>
          <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
        </group>
        <group group_id="P2">
          <title>Sham</title>
          <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active</title>
          <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
        </group>
        <group group_id="B2">
          <title>Sham</title>
          <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</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="5"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="9"/>
          </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="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </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="49.2" spread="10.2"/>
                    <measurement group_id="B2" value="40.5" spread="14.5"/>
                    <measurement group_id="B3" value="45.3" spread="12.6"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</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>Black or African American</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>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</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>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>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Brief Assessment of Cognition in Schizophrenia (BACS) Composite T-score Score at Baseline</title>
          <description>The Brief Assessment of Cognition in Schizophrenia (BACS) represents cognitive ability of people with schizophrenia, where scores from six sub-scales of cognition were normalized to a composite T-score in which the normalized T-score has a mean of 50 and S.D. of 10 of the reference groups, where a higher score significantly above the mean indicates greater cognitive ability. Alternatively, scoring significantly below the mean would indicate lower cognitive ability as reflected in the data.</description>
          <units>T-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.75" spread="10.10"/>
                    <measurement group_id="B2" value="33.5" spread="10.66"/>
                    <measurement group_id="B3" value="33.62" spread="10.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Working Memory Function</title>
        <description>Changes in scores for working memory performance accuracy will serve as dependent measure for testing the hypothesis that rTMS improves working memory. Working memory performance was assessed using a non-standardized task developed in house, which is basically a Sterberg style delayed response task in which memoranda are displayed and are to be remembered across a short delay period. The hypothesis will be supported if the investigators find greater working memory difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scores will be reported as a change in percent accuracy during this working memory task, where higher percent accuracy is better and scores range from -100% to 100%.</description>
        <time_frame>before treatment and after 6-week treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
          </group>
          <group group_id="O2">
            <title>Sham</title>
            <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Working Memory Function</title>
          <description>Changes in scores for working memory performance accuracy will serve as dependent measure for testing the hypothesis that rTMS improves working memory. Working memory performance was assessed using a non-standardized task developed in house, which is basically a Sterberg style delayed response task in which memoranda are displayed and are to be remembered across a short delay period. The hypothesis will be supported if the investigators find greater working memory difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scores will be reported as a change in percent accuracy during this working memory task, where higher percent accuracy is better and scores range from -100% to 100%.</description>
          <units>% change in Working Memory Task Accuracy</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.28" spread="12.95577091"/>
                    <measurement group_id="O2" value="-5.9" spread="15.55040192"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.849</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>1.38</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Neurophysiologic Function</title>
        <description>Gamma oscillation is viewed as a measure of neurophysiologic function. The investigators will be conducting task-evoked electroencephalography (EEG) to measure gamma oscillation before and after rTMS. It is predicted that the intervention will improve gamma oscillations.</description>
        <time_frame>before treatment and after 6-week treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
          </group>
          <group group_id="O2">
            <title>Sham</title>
            <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Neurophysiologic Function</title>
          <description>Gamma oscillation is viewed as a measure of neurophysiologic function. The investigators will be conducting task-evoked electroencephalography (EEG) to measure gamma oscillation before and after rTMS. It is predicted that the intervention will improve gamma oscillations.</description>
          <units>wavelet coefficient in dB</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread=".025"/>
                    <measurement group_id="O2" value="0" spread=".03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Level of Everyday Functioning</title>
        <description>Changes in Global Functioning Scale scores (GF) will serve as dependent measure for testing the hypothesis that rTMS improves functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05.&#xD;
Scale's values range from a minimum score of 1 to a maximum score of 10, with a higher score means better functioning.</description>
        <time_frame>before treatment and after 6-week treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
          </group>
          <group group_id="O2">
            <title>Sham</title>
            <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Level of Everyday Functioning</title>
          <description>Changes in Global Functioning Scale scores (GF) will serve as dependent measure for testing the hypothesis that rTMS improves functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05.&#xD;
Scale's values range from a minimum score of 1 to a maximum score of 10, with a higher score means better functioning.</description>
          <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="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="3.1"/>
                    <measurement group_id="O2" value="-.5" spread="1.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>.782</p_value>
            <p_value_desc>t = 0.287</p_value_desc>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in General Cognitive Ability</title>
        <description>Changes in Brief Assessment of Cognition (BACS) score will serve as a dependent measure for testing the hypothesis that rTMS improves cognitive functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Data will be reported as change in Z-score on the scale, where a higher value means a better outcome, with scores ranging from -3 to 3.</description>
        <time_frame>before treatment and after 6-week treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
          </group>
          <group group_id="O2">
            <title>Sham</title>
            <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in General Cognitive Ability</title>
          <description>Changes in Brief Assessment of Cognition (BACS) score will serve as a dependent measure for testing the hypothesis that rTMS improves cognitive functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Data will be reported as change in Z-score on the scale, where a higher value means a better outcome, with scores ranging from -3 to 3.</description>
          <units>Z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.104" spread=".216"/>
                    <measurement group_id="O2" value=".505" spread=".374"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for one month after the initiation of the intervention</time_frame>
      <desc>No difference in definitions used.</desc>
      <group_list>
        <group group_id="E1">
          <title>Active</title>
          <description>Subjects will receive actual rTMS treatment.&#xD;
Repetitive transcranial magnetic stimulation: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.</description>
        </group>
        <group group_id="E2">
          <title>Sham</title>
          <description>Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.&#xD;
Sham: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric Hospitalization</sub_title>
                <description>Hospitalization likely not causally related to study participation since it was triggered by drug use.</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </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="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Jong Yoon</name_or_title>
      <organization>Palo Alto VA</organization>
      <phone>510-220-7086</phone>
      <email>jhyoon1@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/NCT03037983
org study id: D2382-P
secondary id: 12246865
secondary id: 38101
nct id: NCT03037983
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
The purpose of this study is to determine whether repetitive transcranial magnetic
      stimulation (rTMS) is effective in remediating cognitive deficits while also improving
      functionality in Veterans with schizophrenia.
High-frequency, repetitive transcranial magnetic stimulation (rTMS) to the dorsolateral
      prefrontal cortex (DLPFC), the dysfunctional brain region most implicated in cognitive
      deficits in schizophrenia, has recently been shown to improve cognition in non-Veteran
      samples with schizophrenia. The investigators' goal is to confirm the efficacy of this
      treatment modality to remediate cognitive deficits and improve functionality in Veterans with
      schizophrenia, as well as to gain a better understanding of the neural mechanisms responsible
      for cognitive deficits and their remediation. The investigators propose conducting a
      small-scale study to generate pilot data supporting the feasibility of conducting rTMS with
      Veterans and the effectiveness of rTMS in this population. In addition, the investigators
      will conduct neurophysiologic experiments to test whether certain neural maker of abnormal
      brain function improves with rTMS.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Supportive Care
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Working Memory Function
time frame: before treatment and after 6-week treatment
description: Changes in scores for working memory performance accuracy will serve as dependent measure for testing the hypothesis that rTMS improves working memory. Working memory performance was assessed using a non-standardized task developed in house, which is basically a Sterberg style delayed response task in which memoranda are displayed and are to be remembered across a short delay period. The hypothesis will be supported if the investigators find greater working memory difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Scores will be reported as a change in percent accuracy during this working memory task, where higher percent accuracy is better and scores range from -100% to 100%.
measure: Change in Neurophysiologic Function
time frame: before treatment and after 6-week treatment
description: Gamma oscillation is viewed as a measure of neurophysiologic function. The investigators will be conducting task-evoked electroencephalography (EEG) to measure gamma oscillation before and after rTMS. It is predicted that the intervention will improve gamma oscillations.
measure: Change in Level of Everyday Functioning
time frame: before treatment and after 6-week treatment
description: Changes in Global Functioning Scale scores (GF) will serve as dependent measure for testing the hypothesis that rTMS improves functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05.
Scale's values range from a minimum score of 1 to a maximum score of 10, with a higher score means better functioning.
measure: Change in General Cognitive Ability
time frame: before treatment and after 6-week treatment
description: Changes in Brief Assessment of Cognition (BACS) score will serve as a dependent measure for testing the hypothesis that rTMS improves cognitive functioning. The hypothesis will be supported if the investigators find greater GF-difference in the active compared to the sham-rTMS-treated groups as revealed by t-tests and two-sided tests at an alpha level of 0.05. Data will be reported as change in Z-score on the scale, where a higher value means a better outcome, with scores ranging from -3 to 3.
arm group label: Active rTMS
arm group type: Active Comparator
description: Subjects will receive actual rTMS treatment.
arm group label: Sham rTMS
arm group type: Sham Comparator
description: Subjects will attend and sit through the session, but no rTMS treatment will be actually delivered to them.
intervention type: Device
intervention name: Repetitive transcranial magnetic stimulation
description: rTMS is a non-invasive procedure, in which the administration of a transient magnetic field induces electrical currents in specific, targeted brain regions. The intervention will be administered in 20 sessions lasting 50 minutes each over the course of 2-6 weeks. Up to two sessions may be scheduled per day with a one-hour interval in-between.
arm group label: Active rTMS
other name: rTMS
intervention type: Device
intervention name: Sham
description: Subjects will still attend treatment sessions as outlined in the rTMS intervention. However, the device will not deliver any stimulation to the subject.
arm group label: Sham rTMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jong H. Yoon, MD
role: Principal Investigator
affiliation: VA Palo Alto Health Care System, Palo Alto, CA
facility: 
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Psychotic Disorders
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 