<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/NCT02975973</url>
  </required_header>
  <id_info>
    <org_study_id>H-41815</org_study_id>
    <nct_id>NCT02975973</nct_id>
  </id_info>
  <brief_title>Prefrontal Cortical Engagement Through Non-Invasive Brain Stimulation in Schizophrenia</brief_title>
  <official_title>Prefrontal Cortical Engagement Through Non-Invasive Brain Stimulation in Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Baylor College of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Baylor College of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and&#xD;
      poorly treated by current medications. This study investigates transcranial direct current&#xD;
      stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain&#xD;
      function - as a novel therapeutic for cognition in schizophrenia. Integrating&#xD;
      neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS effects&#xD;
      on cognition by verifying therapeutic target engagement, evaluating the tolerability of tDCS&#xD;
      sessions, and optimizing treatment parameters.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly&#xD;
      remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC)&#xD;
      function underlie core impairments such as in cognitive control and thus represent a critical&#xD;
      target for novel therapeutics. Initial studies indicate transcranial direct-current&#xD;
      stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While tDCS&#xD;
      potentially represents an exciting, novel therapeutic advance, a number of basic questions&#xD;
      should be addressed prior to conducting larger-scale clinical trials, including: verifying&#xD;
      therapeutic target engagement, optimizing treatment parameters, and evaluating for meaningful&#xD;
      clinical effects. Recent studies employing tDCS to enhance prefrontal cortical function in&#xD;
      schizophrenia applied stimulating electrodes over the left frontal scalp region, putatively&#xD;
      targeting the left DLPFC. However, explicit confirmation of such target engagement is&#xD;
      lacking. Further, EEG studies have demonstrated close links of frontal cortical gamma&#xD;
      oscillations to cognitive control processes but modulation of this critical physiologic&#xD;
      process has not been investigated. Accordingly, the primary aim of this study is to employ&#xD;
      multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and modulation&#xD;
      of frontal gamma activity (EEG) by tDCS. This study will also investigate the optimization of&#xD;
      tDCS application parameters. Analogous to dose-finding investigations in drug studies, we&#xD;
      will conduct a parametric investigation of optimal current strengths. Also, while there is&#xD;
      extensive evidence for tolerability of single session tDCS, confirmation of feasibility of&#xD;
      multisession optimized protocols in schizophrenia is lacking and so will be explicitly&#xD;
      evaluated.&#xD;
&#xD;
      In summary, a successful outcome of this study would provide tDCS the sound mechanistic and&#xD;
      methodologic basis for more definitive testing in large-scale clinical trials as a highly&#xD;
      innovative therapeutic intervention for cognitive impairments in schizophrenia.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>November 2016</start_date>
  <completion_date type="Actual">June 2019</completion_date>
  <primary_completion_date type="Actual">June 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging</measure>
    <time_frame>1 week</time_frame>
    <description>Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations</measure>
    <time_frame>1 week</time_frame>
    <description>Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Optimal tDCS Strength for DLPFC Engagement</measure>
    <time_frame>1 Week</time_frame>
    <description>Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tolerability and Feasibility of Multi-session tDCS in Schizophrenia</measure>
    <time_frame>1 week</time_frame>
    <description>The percentage of participants able to complete the full study.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">15</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Psychosis</condition>
  <arm_group>
    <arm_group_label>2.5mA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>2.0mA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1.5mA</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>0mA</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>transcranial direct current stimulation</intervention_name>
    <description>transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
    <arm_group_label>0mA</arm_group_label>
    <arm_group_label>1.5mA</arm_group_label>
    <arm_group_label>2.0mA</arm_group_label>
    <arm_group_label>2.5mA</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. ages 18-35 years;&#xD;
&#xD;
          2. within first five years of antipsychotic treatment;&#xD;
&#xD;
          3. on stable doses of antipsychotic medication for at least one month;&#xD;
&#xD;
          4. Clinically stable as defined by Clinical Global Impression-Severity scale (CGI-S) less&#xD;
             than or equal to 4 (moderately ill);&#xD;
&#xD;
          5. Mild to severe cognitive impairment in MATRICS Consensus Cognitive Battery (composite&#xD;
             scores &lt;40);&#xD;
&#xD;
          6. DSM-5 MINI 7.0.2 criteria for schizophrenia or schizoaffective by patient SCID&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Mental retardation as defined by pre-morbid IQ by Wechsler Test of Adult Reading at&#xD;
             screening &lt;70 or Spanish Word Accentuation Test;&#xD;
&#xD;
          2. significant head injury;&#xD;
&#xD;
          3. History of severe medical or neurological illnesses&#xD;
&#xD;
          4. pregnancy or postpartum (&lt;6 weeks after delivery or miscarriage);&#xD;
&#xD;
          5. inability to provide informed consent;&#xD;
&#xD;
          6. significant color blindness that affects task performance;&#xD;
&#xD;
          7. Positive urine drug screen (exception for marijuana) or presence of substance use&#xD;
             disorder within 1 month;&#xD;
&#xD;
          8. Currently on benzodiazepines or mood stabilizers affecting GABA&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Raymond Cho, M.D., M.Sc.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Baylor College of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Baylor College of Medicine</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2020</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <results_first_submitted>June 29, 2020</results_first_submitted>
  <results_first_submitted_qc>November 4, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">November 25, 2020</results_first_posted>
  <last_update_submitted>November 4, 2020</last_update_submitted>
  <last_update_submitted_qc>November 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">November 25, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Baylor College of Medicine</investigator_affiliation>
    <investigator_full_name>Raymond Cho</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>tDCS</keyword>
  <keyword>cognitive control</keyword>
  <keyword>EEG</keyword>
  <keyword>gamma oscillations</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Data will be open to sharing after primary findings of study have been published</ipd_description>
  </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>April 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT02975973/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The reason we have fewer subjects randomized than enrolled is that some participants did not meet criteria to be randomized. These subjects were consented and completed many assessments, but were ultimately not randomized due to how they scored on some assessments. For instance, some peoples MCCB score was too high to be randomized into the study.</recruitment_details>
      <pre_assignment_details>The primary reasons for ineligibility were not meeting the early psychosis criterion (&lt; 5 years of treatment), not taking any medication, and drug use. There were also many who did not even enter screening due to the assessment that they would highly likely not meet the threshold of requirement cognitive impairment (MATRICS score 40).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>2.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="P2">
          <title>2.0mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="P3">
          <title>1.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="P4">
          <title>0mA (Active Placebo)</title>
          <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>2.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="B2">
          <title>2.0mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="B3">
          <title>1.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="B4">
          <title>0mA (Active Placebo)</title>
          <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="B5">
          <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="1"/>
            <count group_id="B2" value="2"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="4"/>
            <count group_id="B5" value="8"/>
          </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="8"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="22" spread="0"/>
                    <measurement group_id="B2" value="26" spread="3.65"/>
                    <measurement group_id="B3" value="22" spread="0"/>
                    <measurement group_id="B4" value="23" spread="2.44"/>
                    <measurement group_id="B5" value="24" spread="2.66"/>
                  </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="1"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="6"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" 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="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MCCB Score</title>
          <description>Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB).&#xD;
Intended to provide a relatively brief evaluation of key cognitive domains that are relevant to schizophrenia and related disorders, the battery is appropriate for use as an outcome measure for clinical trials of cognition-enhancing drugs, when studying cognitive remediation, to measure cognitive change, and as a cognitive reference point for nonintervention studies of schizophrenia and other severe psychiatric disorders.&#xD;
Higher scores are better.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15" spread="0"/>
                    <measurement group_id="B2" value="17.5" spread="4.95"/>
                    <measurement group_id="B3" value="35" spread="0"/>
                    <measurement group_id="B4" value="32" spread="12.72"/>
                    <measurement group_id="B5" value="26.6" spread="11.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging</title>
        <description>Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance.</description>
        <time_frame>1 week</time_frame>
        <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
        <group_list>
          <group group_id="O1">
            <title>2.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O2">
            <title>2.0mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O3">
            <title>1.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O4">
            <title>0mA (Active Placebo)</title>
            <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
        </group_list>
        <measure>
          <title>tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging</title>
          <description>Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance.</description>
          <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations</title>
        <description>Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance</description>
        <time_frame>1 week</time_frame>
        <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
        <group_list>
          <group group_id="O1">
            <title>2.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O2">
            <title>2.0mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O3">
            <title>1.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O4">
            <title>0mA (Active Placebo)</title>
            <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
        </group_list>
        <measure>
          <title>tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations</title>
          <description>Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance</description>
          <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Optimal tDCS Strength for DLPFC Engagement</title>
        <description>Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA)</description>
        <time_frame>1 Week</time_frame>
        <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
        <group_list>
          <group group_id="O1">
            <title>2.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O2">
            <title>2.0mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O3">
            <title>1.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O4">
            <title>0mA (Active Placebo)</title>
            <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
        </group_list>
        <measure>
          <title>Optimal tDCS Strength for DLPFC Engagement</title>
          <description>Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA)</description>
          <population>Our analytic strategy involved defining regions of interest (ROI) derived from group averages across all study subjects but due to unforeseen circumstances, we recruited far too few subjects to derive meaningful group averages. Individual subject and by extension, condition-specific averages that are based on such ROIs, could therefore not be derived. However, we will upload our raw data to the National Data Archive to be accessed for any potential analyses with data pooled from other studies.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tolerability and Feasibility of Multi-session tDCS in Schizophrenia</title>
        <description>The percentage of participants able to complete the full study.</description>
        <time_frame>1 week</time_frame>
        <population>Due to unforeseen circumstances, we were unable to sufficiently recruit enough subjects to complete the originals plans for analysis. The percentages below are the percent of subjects who completed each condition.</population>
        <group_list>
          <group group_id="O1">
            <title>2.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O2">
            <title>2.0mA</title>
            <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O3">
            <title>1.5mA</title>
            <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
          <group group_id="O4">
            <title>0mA (Active Placebo)</title>
            <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
          </group>
        </group_list>
        <measure>
          <title>Tolerability and Feasibility of Multi-session tDCS in Schizophrenia</title>
          <description>The percentage of participants able to complete the full study.</description>
          <population>Due to unforeseen circumstances, we were unable to sufficiently recruit enough subjects to complete the originals plans for analysis. The percentages below are the percent of subjects who completed each condition.</population>
          <units>percentage of participants completed</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
                <count group_id="O2" value="2"/>
                <count group_id="O3" value="1"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="50"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Two Weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>2.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="E2">
          <title>2.0mA</title>
          <description>Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="E3">
          <title>1.5mA</title>
          <description>Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
        <group group_id="E4">
          <title>0mA (Active Placebo)</title>
          <description>This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.&#xD;
transcranial direct current stimulation: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="1"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Exacerbation of Psychotic Symptoms</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Minor Burn</sub_title>
                <description>Minor burn at location of tDCS electrode placement.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="4"/>
              </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>
    <limitations_and_caveats>Despite concerted and exhaustive subject recruitment efforts, the total number of patients completing the protocol was minimal. As such the sample size was inadequate for deriving any meaningful descriptive statistics or statistical comparisons.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Raymond Cho</name_or_title>
      <organization>Baylor College of Medicine</organization>
      <phone>713-798-7781</phone>
      <email>Raymond.Cho@bcm.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/NCT02975973
org study id: H-41815
nct id: NCT02975973
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Cognitive impairments in schizophrenia are the most debilitating aspect of the illness and
      poorly treated by current medications. This study investigates transcranial direct current
      stimulation (tDCS) - a safe, noninvasive weak electrical current delivery to stimulate brain
      function - as a novel therapeutic for cognition in schizophrenia. Integrating
      neurostimulation, electrophysiology and neuroimaging, this project aims to study tDCS effects
      on cognition by verifying therapeutic target engagement, evaluating the tolerability of tDCS
      sessions, and optimizing treatment parameters.
Cognitive deficits are a strong predictor of functional outcome in schizophrenia, yet poorly
      remediated by current treatments. Disturbances in dorsolateral prefrontal cortex (DLPFC)
      function underlie core impairments such as in cognitive control and thus represent a critical
      target for novel therapeutics. Initial studies indicate transcranial direct-current
      stimulation (tDCS) may be effective in reducing symptoms due to DLPFC dysfunction. While tDCS
      potentially represents an exciting, novel therapeutic advance, a number of basic questions
      should be addressed prior to conducting larger-scale clinical trials, including: verifying
      therapeutic target engagement, optimizing treatment parameters, and evaluating for meaningful
      clinical effects. Recent studies employing tDCS to enhance prefrontal cortical function in
      schizophrenia applied stimulating electrodes over the left frontal scalp region, putatively
      targeting the left DLPFC. However, explicit confirmation of such target engagement is
      lacking. Further, EEG studies have demonstrated close links of frontal cortical gamma
      oscillations to cognitive control processes but modulation of this critical physiologic
      process has not been investigated. Accordingly, the primary aim of this study is to employ
      multimodal imaging to explicitly test for the assumed DLPFC engagement (fMRI) and modulation
      of frontal gamma activity (EEG) by tDCS. This study will also investigate the optimization of
      tDCS application parameters. Analogous to dose-finding investigations in drug studies, we
      will conduct a parametric investigation of optimal current strengths. Also, while there is
      extensive evidence for tolerability of single session tDCS, confirmation of feasibility of
      multisession optimized protocols in schizophrenia is lacking and so will be explicitly
      evaluated.

      In summary, a successful outcome of this study would provide tDCS the sound mechanistic and
      methodologic basis for more definitive testing in large-scale clinical trials as a highly
      innovative therapeutic intervention for cognitive impairments in schizophrenia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: tDCS Engagement of DLPFC Activity Indexed by fMRI BOLD Imaging
time frame: 1 week
description: Change from Baseline to week 1 as measured by modulation of fMRI BOLD signal in DLPFC in the context of cognitive control task performance.
measure: tDCS Engagement of DLPFC Activity Indexed by Modulation of Frontal Cortical Gamma Oscillations
time frame: 1 week
description: Change from Baseline to week 1 as measured by EEG frontal gamma oscillations in the context of cognitive control task performance
measure: Optimal tDCS Strength for DLPFC Engagement
time frame: 1 Week
description: Change from baseline to 1 week in DLPFC engagement across conditions (1.5 vs 2.0 vs 2.5 mA)
measure: Tolerability and Feasibility of Multi-session tDCS in Schizophrenia
time frame: 1 week
description: The percentage of participants able to complete the full study.
arm group label: 2.5mA
arm group type: Experimental
description: Active stimulation group will receive 20 minutes of 2.5 mA transcranial direct current stimulation.
arm group label: 2.0mA
arm group type: Experimental
description: Active stimulation group will receive 20 minutes of 2.0 mA transcranial direct current stimulation.
arm group label: 1.5mA
arm group type: Experimental
description: Active stimulation group will receive 20 minutes of 1.5 mA transcranial direct current stimulation.
arm group label: 0mA
arm group type: Sham Comparator
description: This will be an active sham involving transcranial direct current stimulation, though stimulation will be brief (15 msec) and have low current (0.11 mA) pulses every 550 ms.
intervention type: Device
intervention name: transcranial direct current stimulation
description: transcranial direct current stimulation (tDCS) is a safe, noninvasive, weak electrical current delivery that stimulates brain function. It is a novel therapeutic for cognition in schizophrenia.
arm group label: 0mA
arm group label: 1.5mA
arm group label: 2.0mA
arm group label: 2.5mA
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: No
last name: Raymond Cho, M.D., M.Sc.
role: Principal Investigator
affiliation: Baylor College of Medicine
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Baylor College of Medicine
investigator full name: Raymond Cho
investigator title: Professor
mesh term: Schizophrenia
sharing ipd: Yes
ipd description: Data will be open to sharing after primary findings of study have been published
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Despite concerted and exhaustive subject recruitment efforts, the total number of patients completing the protocol was minimal. As such the sample size was inadequate for deriving any meaningful descriptive statistics or statistical comparisons.
point of contact: 