<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/NCT02237417</url>
  </required_header>
  <id_info>
    <org_study_id>IRB_00073657</org_study_id>
    <nct_id>NCT02237417</nct_id>
  </id_info>
  <brief_title>Study of the Impact of Aripiprazole (Abilify®) Once Monthly Versus Standard of Care Oral Antipsychotic Medications on Changes in Brain Structure and Metabolism</brief_title>
  <official_title>A Randomized, Open Label, Parallel Group, Study of the Impact of Aripiprazole (Abilify®) Once Monthly Versus Standard of Care Oral Antipsychotic Medications on Changes in Brain Structure and Metabolism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Deborah Yurgelun-Todd</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Otsuka America Pharmaceutical</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 4, randomized, open-label, parallel group study designed to assess the&#xD;
      clinical and biological effects of 12 months of treatment with long acting intramuscular (IM)&#xD;
      aripiprazole (Abilify®) as measured by clinical and behavioral measures, and changes on&#xD;
      magnetic resonance imaging (MRI) scans in subjects with schizophrenia compared with SOC oral&#xD;
      antipsychotic medications and compared with a healthy control group.&#xD;
&#xD;
      It is hypothesized that improved treatment compliance will lead to fewer white matter changes&#xD;
      in the brain. Fewer white matter changes will be demonstrated via neuroimaging as increased&#xD;
      FA and BPF values in the prefrontal region, and an increase in metabolites in a voxel&#xD;
      centered on the anterior cingulate cortex (ACC) as seen with MRS. Therefore, the aim of this&#xD;
      study is to examine the structural and metabolic effects of aripiprazole (Abilify®) once&#xD;
      monthly in patients with schizophrenia using MRI techniques and to examine these effects in&#xD;
      association with cognitive and clinical measures.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 1, 2014</start_date>
  <completion_date type="Actual">July 30, 2020</completion_date>
  <primary_completion_date type="Actual">November 30, 2018</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Changes in Fractional Anisotropy (FA)</measure>
    <time_frame>12 months</time_frame>
    <description>To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Gamma Aminobutyric Acid (GABA)</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>To determine if proton metabolites, specifically gamma aminobutyric acid (GABA), glutamine, and glutamate, are altered in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in Regional White Matter and Gray Matter Volume</measure>
    <time_frame>6 and 12 months</time_frame>
    <description>To determine if there are differences in regional white matter and gray matter volume in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Association Between Clinical and Neurocognitive Variables and FA, BPF, and Proton Metabolic Concentrations</measure>
    <time_frame>12 months</time_frame>
    <description>To determine if there is a demonstrated association between clinical and neurocognitive variables and FA, BPF, and proton metabolite concentrations in subjects with schizophrenia receiving SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®).</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Healthy Control</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Individuals with Schizophrenia (Group A)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Individuals with Schizophrenia (Group B)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Standard of Care Oral antipsychotics</intervention_name>
    <description>A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.</description>
    <arm_group_label>Individuals with Schizophrenia (Group A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>IM aripiprazole once monthly</intervention_name>
    <description>A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.</description>
    <arm_group_label>Individuals with Schizophrenia (Group B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>No Treatment</intervention_name>
    <description>A total of 15 healthy controls will participate in the study and will not receive medication</description>
    <arm_group_label>Healthy Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria for All Subjects&#xD;
&#xD;
          -  Are able to provide written informed consent.&#xD;
&#xD;
          -  Are male and female subjects 18 to 35 years of age, inclusive, at time of informed&#xD;
             consent.&#xD;
&#xD;
        Inclusion Criteria for Subjects with Schizophrenia&#xD;
&#xD;
          -  Have a current diagnosis of schizophrenia as defined by DSM IV-TR criteria and a&#xD;
             history of the illness for at least 1 year prior to screening and at least two prior&#xD;
             psychotic episodes based on medical records or a qualified and reliable health care&#xD;
             provider.&#xD;
&#xD;
          -  Require, in the investigator's judgment, chronic treatment with an antipsychotic&#xD;
             medication.&#xD;
&#xD;
          -  Are able to understand the nature of the study and follow protocol requirements,&#xD;
             including the prescribed dosage regimens, tablet ingestion, IM depot injection, and&#xD;
             discontinuation of prohibited concomitant medications, read and understand the written&#xD;
             word in order to complete subject-reported outcomes measures, and be reliably rated on&#xD;
             assessment scales.&#xD;
&#xD;
          -  Are male and female subjects who are surgically sterile (i.e., have undergone&#xD;
             orchiectomy or hysterectomy, respectively; female subjects who have been&#xD;
             postmenopausal for at least 12 consecutive months; or male and female subjects who&#xD;
             agree to remain abstinent or to practice double barrier forms of birth control from&#xD;
             trial screening through 30 days (for females) and 90 days (for males) from the last&#xD;
             dose of IMP for SOC oral antipsychotics and 150 days for females and 180 days for&#xD;
             males for aripiprazole depot. If employing birth control, two of the following&#xD;
             precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine&#xD;
             device, birth control pill, birth control implant, birth control depot injections,&#xD;
             condom, or sponge with spermicide.&#xD;
&#xD;
        Exclusion Criteria All Subjects&#xD;
&#xD;
          -  Presence of any metal implants, pacemakers, unremovable prosthetic device, or other&#xD;
             device or situation that may preclude imaging&#xD;
&#xD;
          -  History of a head injury with loss of consciousness &gt; 5 minutes&#xD;
&#xD;
          -  Has a significant medical condition that would expose the subject to undue risk or&#xD;
             interfere with study assessments.&#xD;
&#xD;
        Exclusion Criteria for Subjects with Schizophrenia&#xD;
&#xD;
          -  Has a current DSM-IV-TR diagnosis other than schizophrenia, including schizophreniform&#xD;
             disorder, schizoaffective disorder, major depressive disorder, bipolar disorder,&#xD;
             delirium, dementia, amnestic or other cognitive disorders. Also excluded are subjects&#xD;
             with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial&#xD;
             personality disorder.&#xD;
&#xD;
          -  Is considered resistant/refractory to antipsychotic treatment by history (failed two&#xD;
             prior antipsychotic medication trials) or response only to clozapine.&#xD;
&#xD;
          -  Has a significant risk of violent behavior or a significant risk of committing suicide&#xD;
             based on history or investigator's discretion.&#xD;
&#xD;
          -  Has met DSM-IV-TR criteria for any significant substance use disorder within 3 months&#xD;
             prior to screening, excluding caffeine, nicotine, or marijuana.&#xD;
&#xD;
          -  Is known to be allergic, intolerant, or unresponsive to prior treatment with&#xD;
             aripiprazole or other quinolinones, or hypersensitivity to antipsychotic agents,&#xD;
             including aripiprazole.&#xD;
&#xD;
          -  Has a history of neuroleptic malignant syndrome or clinically significant tardive&#xD;
             dyskinesia at screening per the investigator's discretion.&#xD;
&#xD;
          -  Has a history of seizures or any other medical condition that would expose the subject&#xD;
             to undue risk or interfere with study assessments.&#xD;
&#xD;
          -  Is involuntarily incarcerated.&#xD;
&#xD;
          -  Has undergone electroconvulsive therapy in the 2 years prior to enrollment in the&#xD;
             study.&#xD;
&#xD;
          -  Has used an investigational agent or has participated in a clinical study with&#xD;
             aripiprazole IM depot or any other antipsychotic depot preparation within 30 days of&#xD;
             screening.&#xD;
&#xD;
          -  Has clinically significant abnormalities in laboratory test results, vital signs, or&#xD;
             ECG results.&#xD;
&#xD;
          -  Requires more than one benzodiazepine beyond screening (e.g., lorazepam and oxazepam).&#xD;
&#xD;
          -  Fails to washout from prohibited concomitant medications, including the use of or&#xD;
             CYP3A4 inducers, a second antipsychotic, antidepressants (including monoamine oxidase&#xD;
             inhibitors), and mood stabilizers.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>35 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Deborah Yurgelun-Todd, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Utah</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Utah</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2021</verification_date>
  <study_first_submitted>September 3, 2014</study_first_submitted>
  <study_first_submitted_qc>September 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 11, 2014</study_first_posted>
  <results_first_submitted>October 12, 2020</results_first_submitted>
  <results_first_submitted_qc>January 26, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 15, 2021</results_first_posted>
  <last_update_submitted>January 26, 2021</last_update_submitted>
  <last_update_submitted_qc>January 26, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Utah</investigator_affiliation>
    <investigator_full_name>Deborah Yurgelun-Todd</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>MRI</keyword>
  <keyword>Imaging</keyword>
  <keyword>Antipsychotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Aripiprazole</mesh_term>
    <mesh_term>Antipsychotic Agents</mesh_term>
  </intervention_browse>
  <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>July 29, 2013</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02237417/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>June 1, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02237417/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Healthy Control</title>
          <description>No Treatment: A total of 15 healthy controls will participate in the study and will not receive medication</description>
        </group>
        <group group_id="P2">
          <title>Individuals With Schizophrenia (Group A)</title>
          <description>Standard of Care Oral antipsychotics: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.</description>
        </group>
        <group group_id="P3">
          <title>Individuals With Schizophrenia (Group B)</title>
          <description>IM aripiprazole once monthly: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="9"/>
                <participants group_id="P3" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Healthy Control</title>
          <description>No Treatment: A total of 15 healthy controls will participate in the study and will not receive medication</description>
        </group>
        <group group_id="B2">
          <title>Individuals With Schizophrenia (Group A)</title>
          <description>Standard of Care Oral antipsychotics: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.</description>
        </group>
        <group group_id="B3">
          <title>Individuals With Schizophrenia (Group B)</title>
          <description>IM aripiprazole once monthly: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.</description>
        </group>
        <group group_id="B4">
          <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="16"/>
            <count group_id="B2" value="15"/>
            <count group_id="B3" value="16"/>
            <count group_id="B4" value="47"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="47"/>
                  </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_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="28" lower_limit="18" upper_limit="50"/>
                    <measurement group_id="B2" value="30" lower_limit="18" upper_limit="50"/>
                    <measurement group_id="B3" value="28" lower_limit="18" upper_limit="50"/>
                    <measurement group_id="B4" value="28" lower_limit="18" upper_limit="50"/>
                  </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="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="13"/>
                    <measurement group_id="B4" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="32"/>
                  </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="1"/>
                    <measurement group_id="B4" value="1"/>
                  </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="16"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Changes in Fractional Anisotropy (FA)</title>
        <description>To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
        <time_frame>12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Healthy Control</title>
            <description>No Treatment: A total of 15 healthy controls will participate in the study and will not receive medication</description>
          </group>
          <group group_id="O2">
            <title>Individuals With Schizophrenia (Group A)</title>
            <description>Standard of Care Oral antipsychotics: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.</description>
          </group>
          <group group_id="O3">
            <title>Individuals With Schizophrenia (Group B)</title>
            <description>IM aripiprazole once monthly: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Changes in Fractional Anisotropy (FA)</title>
          <description>To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Gamma Aminobutyric Acid (GABA)</title>
        <description>To determine if proton metabolites, specifically gamma aminobutyric acid (GABA), glutamine, and glutamate, are altered in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
        <time_frame>6 and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Regional White Matter and Gray Matter Volume</title>
        <description>To determine if there are differences in regional white matter and gray matter volume in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).</description>
        <time_frame>6 and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Association Between Clinical and Neurocognitive Variables and FA, BPF, and Proton Metabolic Concentrations</title>
        <description>To determine if there is a demonstrated association between clinical and neurocognitive variables and FA, BPF, and proton metabolite concentrations in subjects with schizophrenia receiving SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®).</description>
        <time_frame>12 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>1 Year</time_frame>
      <desc>Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign, symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research. Three types of adverse event data are to be reported: &quot;All-Cause Mortality,&quot; &quot;Serious,&quot; and &quot;Other (Not Including Serious)&quot; Adverse Events.</desc>
      <group_list>
        <group group_id="E1">
          <title>Healthy Control</title>
          <description>No Treatment: A total of 15 healthy controls will participate in the study and will not receive medication</description>
        </group>
        <group group_id="E2">
          <title>Individuals With Schizophrenia (Group A)</title>
          <description>Standard of Care Oral antipsychotics: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.</description>
        </group>
        <group group_id="E3">
          <title>Individuals With Schizophrenia (Group B)</title>
          <description>IM aripiprazole once monthly: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
              </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>The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Wilt, Timothy</name_or_title>
      <organization>Otsuka</organization>
      <phone>240.683.3095</phone>
      <email>timothy.wilt@otsuka-us.com</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/NCT02237417
org study id: IRB_00073657
nct id: NCT02237417
lead sponsor: 
collaborator: 
has dmc: Yes
This is a Phase 4, randomized, open-label, parallel group study designed to assess the
      clinical and biological effects of 12 months of treatment with long acting intramuscular (IM)
      aripiprazole (Abilify®) as measured by clinical and behavioral measures, and changes on
      magnetic resonance imaging (MRI) scans in subjects with schizophrenia compared with SOC oral
      antipsychotic medications and compared with a healthy control group.

      It is hypothesized that improved treatment compliance will lead to fewer white matter changes
      in the brain. Fewer white matter changes will be demonstrated via neuroimaging as increased
      FA and BPF values in the prefrontal region, and an increase in metabolites in a voxel
      centered on the anterior cingulate cortex (ACC) as seen with MRS. Therefore, the aim of this
      study is to examine the structural and metabolic effects of aripiprazole (Abilify®) once
      monthly in patients with schizophrenia using MRI techniques and to examine these effects in
      association with cognitive and clinical measures.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants With Changes in Fractional Anisotropy (FA)
time frame: 12 months
description: To determine if there are differences in prefrontal white matter fractional anisotropy (FA) in subjects with schizophrenia from baseline at 12 months of treatment with aripiprazole (Abilify®) once monthly compared with standard of care (SOC) oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).
measure: Changes in Gamma Aminobutyric Acid (GABA)
time frame: 6 and 12 months
description: To determine if proton metabolites, specifically gamma aminobutyric acid (GABA), glutamine, and glutamate, are altered in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).
measure: Changes in Regional White Matter and Gray Matter Volume
time frame: 6 and 12 months
description: To determine if there are differences in regional white matter and gray matter volume in subjects with schizophrenia after 6 and 12 months of treatment with aripiprazole (Abilify®) once monthly compared with SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI (Geodon®)).
measure: Association Between Clinical and Neurocognitive Variables and FA, BPF, and Proton Metabolic Concentrations
time frame: 12 months
description: To determine if there is a demonstrated association between clinical and neurocognitive variables and FA, BPF, and proton metabolite concentrations in subjects with schizophrenia receiving SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®).
arm group label: Healthy Control
arm group type: Other
arm group label: Individuals with Schizophrenia (Group A)
arm group type: Active Comparator
arm group label: Individuals with Schizophrenia (Group B)
arm group type: Active Comparator
intervention type: Drug
intervention name: Standard of Care Oral antipsychotics
description: A total of 15 to 20 subjects with schizophrenia will receive SOC oral antipsychotic medications (e.g., aripiprazole (Abilify®), risperidone (Risperdal®), lurasidone HCI (Latuda®), quetiapine fumarate (Seroquel®), olanzapine (Zyprexa®), and ziprasidone HCI(Geodon®)) or once monthly aripiprazole (Abilify®), PO daily, in accordance with their respective product labeling.
arm group label: Individuals with Schizophrenia (Group A)
intervention type: Drug
intervention name: IM aripiprazole once monthly
description: A total of 30 to 40 subjects with schizophrenia will receive aripiprazole (Abilify®) monthly, at a starting dose of 400 mg IM or an approved dose based on the investigator's judgment and in accordance with product labeling.
arm group label: Individuals with Schizophrenia (Group B)
intervention type: Other
intervention name: No Treatment
description: A total of 15 healthy controls will participate in the study and will not receive medication
arm group label: Healthy Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 35 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Deborah Yurgelun-Todd, PhD
role: Principal Investigator
affiliation: University of Utah
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Utah
investigator full name: Deborah Yurgelun-Todd
investigator title: Professor
mesh term: Schizophrenia
mesh term: Aripiprazole
mesh term: Antipsychotic Agents
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 