<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/NCT02199743</url>
  </required_header>
  <id_info>
    <org_study_id>STU 032012-053</org_study_id>
    <nct_id>NCT02199743</nct_id>
  </id_info>
  <brief_title>Lurasidone Effects on Tissue Glutamate in Schizophrenia</brief_title>
  <official_title>Lurasidone Effects on Tissue Glutamate in Schizophrenia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Texas Southwestern Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Sumitomo Pharma America, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Texas Southwestern Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      24 individuals with schizophrenia or schizoaffective disorders, who are currently considered&#xD;
      stable, will be recruited, screened for entry criteria into a blinded study with a 4-week&#xD;
      randomization to either lurasidone, haloperidol, or perphenazine to examine glutamate-related&#xD;
      outcomes with lurasidone as compared to haloperidol and perphenazine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      At study start all volunteers will be discontinued from their current antipsychotic drug&#xD;
      (APD) and switched to haloperidol 4mg for 5 days. At the end of this discontinuation period,&#xD;
      all baseline symptom ratings and cognition testing will be done, as well as the baseline&#xD;
      imaging procedures. At the end of the baseline procedures, volunteers will be blindly&#xD;
      randomized, either to lurasidone at 40mg (N=12), or to haloperidol at 4mg/d or perphenazine&#xD;
      at 16mg/d (N=12). Doses will increase to 80mg/d lurasidone, 8 mg/d haloperidol, or 32 mg/d of&#xD;
      perphenazine at the beginning of week two. Dose should be stable for the last 3 weeks of&#xD;
      treatment unless side effects are prominent, then the dose can be decreased to 40&#xD;
      lurasidone/4 haloperidol/16 perphenazine mg/d for optimal clinical management. The&#xD;
      randomization strategy will be designed and implemented by the research pharmacist in four&#xD;
      blocks of six volunteers; drug will be dispensed by the research pharmacy according to the&#xD;
      randomization schedule. The randomization will be followed by a four week treatment period at&#xD;
      optimal dose levels. On the last two days of the 4 week stable dosing period, the specified&#xD;
      glutamate outcome measures will be completed (neuroimaging and cognitive testing) along with&#xD;
      all the symptom outcome measures, testing for drug plasma levels, and usual blood safety&#xD;
      measures. Patients will be seen weekly for clinical evaluation; suicidality will be monitored&#xD;
      weekly. All medications other than study drugs will be discontinued, as much as possible, for&#xD;
      the 24-48 hr assessment period. After the evaluation phase, patients will be cross-titrated&#xD;
      back to their original treatment medication and dosing.&#xD;
&#xD;
      This design will generate outcomes from 12 patients on lurasidone vs. 12 patients on&#xD;
      haloperidol/ perphenazine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2013</start_date>
  <completion_date type="Actual">June 2016</completion_date>
  <primary_completion_date type="Actual">June 2016</primary_completion_date>
  <phase>Phase 4</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral Glutamate Levels</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water.&#xD;
More negative values represent less cerebral glutamate levels.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Brief Assessments of Cognition in Schizophrenia Scores (BACS)</measure>
    <time_frame>Baseline and 4 weeks</time_frame>
    <description>Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22).&#xD;
Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <arm_group>
    <arm_group_label>Lurasidone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Perphenazine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lurasidone</intervention_name>
    <description>Compare to haloperidol and perphenazine</description>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_label>Lurasidone</arm_group_label>
    <arm_group_label>Perphenazine</arm_group_label>
    <other_name>Latuda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Haloperidol</intervention_name>
    <description>Compare to lurasidone</description>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_label>Lurasidone</arm_group_label>
    <arm_group_label>Perphenazine</arm_group_label>
    <other_name>Haldol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Perphenazine</intervention_name>
    <description>Compare to lurasidone</description>
    <arm_group_label>Haloperidol</arm_group_label>
    <arm_group_label>Lurasidone</arm_group_label>
    <arm_group_label>Perphenazine</arm_group_label>
    <other_name>Trilafon</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subject at least 18 years old&#xD;
&#xD;
          -  Subject meets criteria diagnosis of schizophrenia or schizoaffective disorder.&#xD;
&#xD;
          -  Subject is not pregnant and is not planning pregnancy within the projected duration of&#xD;
             the study.&#xD;
&#xD;
          -  Female subject who is of reproductive potential agrees to remain abstinent or use&#xD;
             adequate and reliable contraception throughout the study&#xD;
&#xD;
          -  Subject is in good physical health on the basis of medical history, physical&#xD;
             examination, and laboratory screening.&#xD;
&#xD;
          -  Eyesight corrected to 20-40 or better&#xD;
&#xD;
          -  Able to read, speak, and understand English*&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any medications being used as mood stabilizers (i.e., anticonvulsants)&#xD;
&#xD;
          -  Subject currently has a clinically significant medical condition(s) that would pose a&#xD;
             risk to the subject if they were to participate in the study or that might confound&#xD;
             the results of the study.&#xD;
&#xD;
          -  Subject demonstrates evidence of acute/chronic hepatitis which is clinically&#xD;
             significant&#xD;
&#xD;
          -  Subject has a history of malignancy &lt; 5 years prior&#xD;
&#xD;
          -  Subject has a history of neuroleptic malignant syndrome (NMS).&#xD;
&#xD;
          -  Subject has a history of alcohol or substance abuse within 3 months prior to screening&#xD;
             or alcohol or substance dependence within 12 months prior to screening&#xD;
&#xD;
          -  Subject tests positive for drugs of abuse at screening. In the event a subject tests&#xD;
             positive for cannabis, the investigator will evaluate the subject's ability to abstain&#xD;
             from cannabis during the study.&#xD;
&#xD;
          -  Subjects diagnosed with type 1 diabetes&#xD;
&#xD;
          -  Subject has a prolactin concentration &gt; 200 ng/mL at screening&#xD;
&#xD;
          -  Subject has a history or presence of abnormal ECG which is clinically significant&#xD;
&#xD;
          -  Subject has a history of hypersensitivity to more than two distinct chemical classes&#xD;
             of drug (e.g., sulfas and penicillins).&#xD;
&#xD;
          -  Subjects have received depot neuroleptics within 12 weeks prior to randomization.&#xD;
&#xD;
          -  Subject has a history of treatment with clozapine for refractory psychosis and/or&#xD;
             subject has been treated with clozapine within 4 months of randomization.&#xD;
&#xD;
          -  Subject does not have a stable residence for the 3 months prior to randomization.&#xD;
&#xD;
          -  Subject requires treatment with any potent CYP3A4 inhibitors or inducers during the&#xD;
             study.&#xD;
&#xD;
          -  Subject has received electroconvulsive therapy (ECT) within 90 days prior to&#xD;
&#xD;
          -  Subject has been randomized in a prior clinical trial of lurasidone.&#xD;
&#xD;
          -  History of serious head injury with unconsciousness for &gt;30 minutes&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carol A Tamminga, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>UT Southwestern Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.utsouthwestern.edu/labs/schizophrenia/</url>
    <description>Tamminga Lab and Clinic Website</description>
  </link>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 23, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 24, 2014</study_first_posted>
  <results_first_submitted>October 25, 2020</results_first_submitted>
  <results_first_submitted_qc>February 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 1, 2021</results_first_posted>
  <last_update_submitted>February 26, 2021</last_update_submitted>
  <last_update_submitted_qc>February 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 1, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Texas Southwestern Medical Center</investigator_affiliation>
    <investigator_full_name>Carol A. Tamminga</investigator_full_name>
    <investigator_title>Professor of Medicine</investigator_title>
  </responsible_party>
  <keyword>schizophrenia</keyword>
  <keyword>schizoaffective</keyword>
  <keyword>cognition</keyword>
  <keyword>lurasidone</keyword>
  <keyword>Latuda</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Haloperidol</mesh_term>
    <mesh_term>Haloperidol decanoate</mesh_term>
    <mesh_term>Lurasidone Hydrochloride</mesh_term>
    <mesh_term>Perphenazine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>35 individuals initially signed the Informed Consent and began the Screening procedures. Only 24 made it to Randomization, with only 22 making it to the end of the study. Generally participants were discontinued because they were lost to follow-up (which requires 3 telephone calls and a letter) and irregular labs that were exclusionary.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Lurasidone</title>
          <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks&#xD;
This group was compared to the &quot;Non-Lurasidone&quot; group (with both haloperidol and perphenazine together) in the final analysis.</description>
        </group>
        <group group_id="P2">
          <title>Non-Lurasidone</title>
          <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.&#xD;
OR Perphenazine 8mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.&#xD;
Each of these drug groups were treated individually in the study but grouped together into a &quot;Non-Lurasidone&quot; group for analysis.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Lurasidone</title>
          <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks&#xD;
Compare to haloperidol and perphenazine groups combined to lurasidone group.</description>
        </group>
        <group group_id="B2">
          <title>Non-Lurasidone</title>
          <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.&#xD;
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.&#xD;
Compare haloperidol and perphenazine groups combined to lurasidone.</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="14"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="24"/>
          </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="14"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="24"/>
                  </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>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51" lower_limit="34" upper_limit="60"/>
                    <measurement group_id="B2" value="46" lower_limit="36" upper_limit="58"/>
                    <measurement group_id="B3" value="49" lower_limit="34" upper_limit="60"/>
                  </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="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="13"/>
                  </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="14"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cerebral Glutamate Levels</title>
        <description>Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water.&#xD;
More negative values represent less cerebral glutamate levels.</description>
        <time_frame>Baseline and 4 weeks</time_frame>
        <population>Of the original 22 participants, only 15 have both Baseline and Week 4 scans to compare.</population>
        <group_list>
          <group group_id="O1">
            <title>Lurasidone</title>
            <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks&#xD;
This group was compared to the &quot;Non-Lurasidone&quot; group (with both haloperidol and perphenazine together) in the final analysis.</description>
          </group>
          <group group_id="O2">
            <title>Non-Lurasidone</title>
            <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.&#xD;
OR Perphenazine 8mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.&#xD;
Each of these drug groups were treated individually in the study but grouped together into a &quot;Non-Lurasidone&quot; group for analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Cerebral Glutamate Levels</title>
          <description>Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water.&#xD;
More negative values represent less cerebral glutamate levels.</description>
          <population>Of the original 22 participants, only 15 have both Baseline and Week 4 scans to compare.</population>
          <units>relative unit (RU as compared to water)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (week 0)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.434662171" spread="0.741430931"/>
                    <measurement group_id="O2" value="-1.933853656" spread="1.005387144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.412294235" spread="0.952600355"/>
                    <measurement group_id="O2" value="-1.838991525" spread="1.20411535"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Brief Assessments of Cognition in Schizophrenia Scores (BACS)</title>
        <description>Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22).&#xD;
Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.</description>
        <time_frame>Baseline and 4 weeks</time_frame>
        <population>Of the original 22 participants, only 15 have both Baseline and Week 4 to compare.</population>
        <group_list>
          <group group_id="O1">
            <title>Lurasidone</title>
            <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks&#xD;
Compare to haloperidol and perphenazine groups combined to lurasidone group.</description>
          </group>
          <group group_id="O2">
            <title>Non-Lurasidone</title>
            <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.&#xD;
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.&#xD;
Compare haloperidol and perphenazine groups combined to lurasidone.</description>
          </group>
        </group_list>
        <measure>
          <title>Brief Assessments of Cognition in Schizophrenia Scores (BACS)</title>
          <description>Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22).&#xD;
Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.</description>
          <population>Of the original 22 participants, only 15 have both Baseline and Week 4 to compare.</population>
          <units>BACS composite score (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="8"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline (week 0)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.596573107" spread="0.929835487"/>
                    <measurement group_id="O2" value="-1.933853656" spread="1.005387144"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.002433521" spread="1.596431421"/>
                    <measurement group_id="O2" value="-1.500292967" spread="1.477111055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Lurasidone (LUR)</title>
          <description>Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks&#xD;
Compare lurasidone (LUR) group to haloperidol and perphenazine (NONLUR) group</description>
        </group>
        <group group_id="E2">
          <title>NONLUR</title>
          <description>Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.&#xD;
OR Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.&#xD;
Compare haloperidol and perphenazine (NONLUR) group to lurasidone (LUR) group.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>diabetes mellitus</sub_title>
                <description>Participant was monitoring glucose on his own with his PCP. Became sick with pneumonia and had his glucose increase to 315 at time of visit to ER. Was hospitalized for ~1 week. Started on medication for hypertension and insulin for DMII.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Restlessness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Stiffness in jaw</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Debra Bushong, MS, LPC</name_or_title>
      <organization>UT Southwestern Medical Center</organization>
      <phone>214-648-4653</phone>
      <email>debra.bushong@utsouthwestern.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/NCT02199743
org study id: STU 032012-053
nct id: NCT02199743
lead sponsor: 
collaborator: 
has dmc: No
24 individuals with schizophrenia or schizoaffective disorders, who are currently considered
      stable, will be recruited, screened for entry criteria into a blinded study with a 4-week
      randomization to either lurasidone, haloperidol, or perphenazine to examine glutamate-related
      outcomes with lurasidone as compared to haloperidol and perphenazine.
At study start all volunteers will be discontinued from their current antipsychotic drug
      (APD) and switched to haloperidol 4mg for 5 days. At the end of this discontinuation period,
      all baseline symptom ratings and cognition testing will be done, as well as the baseline
      imaging procedures. At the end of the baseline procedures, volunteers will be blindly
      randomized, either to lurasidone at 40mg (N=12), or to haloperidol at 4mg/d or perphenazine
      at 16mg/d (N=12). Doses will increase to 80mg/d lurasidone, 8 mg/d haloperidol, or 32 mg/d of
      perphenazine at the beginning of week two. Dose should be stable for the last 3 weeks of
      treatment unless side effects are prominent, then the dose can be decreased to 40
      lurasidone/4 haloperidol/16 perphenazine mg/d for optimal clinical management. The
      randomization strategy will be designed and implemented by the research pharmacist in four
      blocks of six volunteers; drug will be dispensed by the research pharmacy according to the
      randomization schedule. The randomization will be followed by a four week treatment period at
      optimal dose levels. On the last two days of the 4 week stable dosing period, the specified
      glutamate outcome measures will be completed (neuroimaging and cognitive testing) along with
      all the symptom outcome measures, testing for drug plasma levels, and usual blood safety
      measures. Patients will be seen weekly for clinical evaluation; suicidality will be monitored
      weekly. All medications other than study drugs will be discontinued, as much as possible, for
      the 24-48 hr assessment period. After the evaluation phase, patients will be cross-titrated
      back to their original treatment medication and dosing.

      This design will generate outcomes from 12 patients on lurasidone vs. 12 patients on
      haloperidol/ perphenazine.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Cerebral Glutamate Levels
time frame: Baseline and 4 weeks
description: Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water.
More negative values represent less cerebral glutamate levels.
measure: Brief Assessments of Cognition in Schizophrenia Scores (BACS)
time frame: Baseline and 4 weeks
description: Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22).
Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure.
arm group label: Lurasidone
arm group type: Active Comparator
description: Lurasidone 40mg po qhs with food x 1 week; Lurasidone 80mg po qhs with food x 3 weeks
arm group label: Haloperidol
arm group type: Active Comparator
description: Haloperidol 4mg po qhs with food x 1 week; Haloperidol 8mg po qhs with food x 3 weeks.
arm group label: Perphenazine
arm group type: Active Comparator
description: Perphenazine 16mg po qhs with food x 1 week; Perphenazine 32mg po qhs with food x 3 weeks.
intervention type: Drug
intervention name: Lurasidone
description: Compare to haloperidol and perphenazine
arm group label: Haloperidol
arm group label: Lurasidone
arm group label: Perphenazine
other name: Latuda
intervention type: Drug
intervention name: Haloperidol
description: Compare to lurasidone
arm group label: Haloperidol
arm group label: Lurasidone
arm group label: Perphenazine
other name: Haldol
intervention type: Drug
intervention name: Perphenazine
description: Compare to lurasidone
arm group label: Haloperidol
arm group label: Lurasidone
arm group label: Perphenazine
other name: Trilafon
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Carol A Tamminga, M.D.
role: Principal Investigator
affiliation: UT Southwestern Medical Center
facility: 
country: United States
url: http://www.utsouthwestern.edu/labs/schizophrenia/
description: Tamminga Lab and Clinic Website
responsible party type: Principal Investigator
investigator affiliation: University of Texas Southwestern Medical Center
investigator full name: Carol A. Tamminga
investigator title: Professor of Medicine
mesh term: Schizophrenia
mesh term: Psychotic Disorders
mesh term: Haloperidol
mesh term: Haloperidol decanoate
mesh term: Lurasidone Hydrochloride
mesh term: Perphenazine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 