<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/NCT02188121</url>
  </required_header>
  <id_info>
    <org_study_id>2014P001599</org_study_id>
    <nct_id>NCT02188121</nct_id>
  </id_info>
  <brief_title>Fixed Dose Intervention Trial of New England Enhancing Survival in SMI Patients</brief_title>
  <acronym>FITNESS</acronym>
  <official_title>Fixed Dose Intervention Trial of New England Enhancing Survival in Serious Mental Illness Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mclean Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Michael J. Gill Mental Health Clinic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Massachusetts Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dauten Family Center for Bipolar Treatment Innovation at Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Edinburg Center, Bedford MA</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mclean Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Patients with severe mental illness (SMI) die younger than persons in the general population.&#xD;
      Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and&#xD;
      is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the&#xD;
      cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients&#xD;
      receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient&#xD;
      adherence are central problems to reducing cardiovascular risks for patients with SMI. To&#xD;
      address these problems, we propose to conduct a multi-site, open-label, randomized controlled&#xD;
      trial comparing an initial treatment strategy of free, fixed-doses of two generic,&#xD;
      cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental&#xD;
      health clinics versus usual treatment. The study will include adult patients (18+ years old)&#xD;
      with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or&#xD;
      psychosis not otherwise specified (NOS) who have received 2GAs treatment within the past six&#xD;
      months from within four mental health clinics in the Boston area. We have three aims: 1) to&#xD;
      compare the proportions of subjects in each arm who are receiving cardiovascular drug&#xD;
      treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in&#xD;
      composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk&#xD;
      factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels,&#xD;
      accounting for variation in adherence over time, using causal inference techniques to&#xD;
      estimate the per-protocol effect of the intervention. Our three aims examine whether this low&#xD;
      cost, streamlined treatment strategy increases the numbers of subjects receiving&#xD;
      cardiovascular prevention therapy and improves cardiovascular risk levels. We will follow&#xD;
      subjects for 12 months, and collect interview and biometric data at baseline and over the&#xD;
      following 12 months. Subjects will have the option to continue for another 12 months, during&#xD;
      which we will continue to collect interview and biometric data, but will not prescribe&#xD;
      cardiovascular medications. This population-based initial treatment strategy could be an&#xD;
      effective and efficient approach for overcoming traditional barriers to cardiovascular&#xD;
      disease prevention within the SMI population. Findings from this study will inform efforts to&#xD;
      improve care and outcomes, and to enhance survival for patients with severe mental illness.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      By design, all subjects in the Intervention arm will start by being under treatment. During&#xD;
      the course of follow-up, we expect that some will stay consistently on treatment, some will&#xD;
      discontinue treatment (become non-adherent), while others will make transitions on and off&#xD;
      treatment in various patterns. In contrast, by design, subjects in the Usual Treatment&#xD;
      (control) arm do not start on treatment; however, some will initiate treatment as a result of&#xD;
      usual clinical care, e.g., primary care physician initiation. At any point we will be&#xD;
      comparing two binary outcomes (on or off treatment) and will use standard methods for&#xD;
      comparing two proportions to test statistical significance and get confidence intervals for&#xD;
      the difference in the percent on treatment in the two arms. Participants who are ineligible&#xD;
      for randomization will be followed similarly to participants in the Usual Treatment Arm, in a&#xD;
      third, non-randomized group, which will be excluded from the primary analysis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>February 2015</start_date>
  <completion_date type="Actual">October 2021</completion_date>
  <primary_completion_date type="Actual">October 2020</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 on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)</measure>
    <time_frame>Baseline to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Low Density Lipoprotein Levels</measure>
    <time_frame>Baseline to 12 months</time_frame>
    <description>Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in Modified Framingham Score as a Summary Cardiovascular Risk Level</measure>
    <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
    <description>The outcome here is the difference in summary risk level changes (e.g., modified Framingham score) between our two study groups, i.e., do intervention subjects experience differential changes in cardiovascular risk levels compared to control subjects. This outcome will be continuously measured (but not necessarily normally distributed).</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Number of Distinct Cardiovascular Prevention Drugs Taken</measure>
    <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
    <description>Similar to primary outcome measure, but here we count the number of distinct cardiovascular prevention drugs taken by the patient as a continuous measure to reflect potential for partial treatment.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Systolic Blood Pressure</measure>
    <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
    <description>Similar to secondary outcome measure but focusing on Systolic Blood Pressure</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Hemoglobin A1C</measure>
    <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
    <description>Similar to secondary outcome measure but focusing on Hemoglobin A1c</description>
  </other_outcome>
  <other_outcome>
    <measure>Change in Percent on Adequate Cardiovascular Prevention Care</measure>
    <time_frame>Baseline to 3 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in Percent on Adequate Cardiovascular Prevention Care</measure>
    <time_frame>Baseline to 6 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Change in Percent on Adequate Cardiovascular Prevention Care</measure>
    <time_frame>Baseline to 9 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Mean Percentage of Follow up Time During Which Each Group is on Adequate Cardiovascular Prevention Care</measure>
    <time_frame>Baseline to 12 months</time_frame>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">227</enrollment>
  <condition>Serious Mental Illness</condition>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <condition>Bipolar Disorder</condition>
  <condition>Cardiovascular Disease</condition>
  <condition>Major Depressive Disorder</condition>
  <condition>Psychosis NOS</condition>
  <arm_group>
    <arm_group_label>Statin and/or Angiotensin Receptor Blocker</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Usual treatment</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Simvastatin</intervention_name>
    <description>3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors</description>
    <arm_group_label>Statin and/or Angiotensin Receptor Blocker</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Losartan</intervention_name>
    <description>Angiotensin II receptor antagonist</description>
    <arm_group_label>Statin and/or Angiotensin Receptor Blocker</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Incident or prevalent cases: schizophrenia, schizoaffective disorder, bipolar&#xD;
             disorder, major depressive disorder, or psychosis NOS (chart diagnosis).&#xD;
&#xD;
          -  Age 18 years and older.&#xD;
&#xD;
          -  Recent treatment with a standing 2GA, e.g., receiving a standing 2GA in the past 6&#xD;
             months.&#xD;
&#xD;
          -  Concomitant psychotropic medications will be allowed.&#xD;
&#xD;
          -  Ongoing treatment of their mental illnesses at one of four study mental health&#xD;
             clinics, defined as entering one of the two-year First Episode Clinic treatment&#xD;
             programs as a de novo patient (new disease) or having been diagnosed &gt;2 years ago and&#xD;
             had at least six visits in the past 12 months (prevalent disease).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  • Unstable/active disease or potential contraindications with both study medications,&#xD;
             e.g., diabetes, unstable angina or recent acute coronary syndrome, pregnancy, very&#xD;
             high risk factors on the screening labs (e.g., A1c&gt;7%), renal failure, liver failure,&#xD;
             or both statin and angiotension drug contraindications.&#xD;
&#xD;
               -  Unable to provide informed consent, e.g., has dementia, developmental disability,&#xD;
                  other cognitive disorder, or fails screening mini-mental status exam (subjects&#xD;
                  with guardians may participate with guardian consent)&#xD;
&#xD;
               -  Receiving active cardiovascular treatment, defined as receiving both a statin or&#xD;
                  ARB in the past three months.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>89 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dost Ongur, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mclean Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McLean Hospital</name>
      <address>
        <city>Belmont</city>
        <state>Massachusetts</state>
        <zip>02478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 8, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <results_first_submitted>October 26, 2022</results_first_submitted>
  <results_first_submitted_qc>October 28, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 22, 2022</results_first_posted>
  <last_update_submitted>January 4, 2023</last_update_submitted>
  <last_update_submitted_qc>January 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 30, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mclean Hospital</investigator_affiliation>
    <investigator_full_name>Dost Ongur</investigator_full_name>
    <investigator_title>Chief of Psychotic Disorders Division at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cardiovascular Diseases</mesh_term>
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Bipolar Disorder</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</mesh_term>
    <mesh_term>Simvastatin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 21, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT02188121/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 10, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/21/NCT02188121/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>23 participants were excluded after enrollment but prior to assignment to a study arm. The reasons for exclusion were vital signs or lab values outside of inclusion criteria, or emergence of details after enrollment that made participant ineligible.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Statin and/or Angiotensin Receptor Blocker</title>
          <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily&#xD;
Simvastatin: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors&#xD;
Losartan: Angiotensin II receptor antagonist</description>
        </group>
        <group group_id="P2">
          <title>Usual Treatment</title>
          <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="99"/>
                <participants group_id="P2" count="105"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="79"/>
                <participants group_id="P2" count="78"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="27"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Statin and/or Angiotensin Receptor Blocker</title>
          <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily&#xD;
Simvastatin: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors&#xD;
Losartan: Angiotensin II receptor antagonist</description>
        </group>
        <group group_id="B2">
          <title>Usual Treatment</title>
          <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</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="99"/>
            <count group_id="B2" value="105"/>
            <count group_id="B3" value="204"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <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="36.0" lower_limit="18" upper_limit="68"/>
                    <measurement group_id="B2" value="38.3" lower_limit="19" upper_limit="74"/>
                    <measurement group_id="B3" value="37.2" lower_limit="18" upper_limit="74"/>
                  </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="35"/>
                    <measurement group_id="B2" value="46"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="64"/>
                    <measurement group_id="B2" value="59"/>
                    <measurement group_id="B3" value="123"/>
                  </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="10"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="85"/>
                    <measurement group_id="B2" value="92"/>
                    <measurement group_id="B3" value="177"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="12"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="70"/>
                    <measurement group_id="B2" value="75"/>
                    <measurement group_id="B3" value="145"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="99"/>
                    <measurement group_id="B2" value="105"/>
                    <measurement group_id="B3" value="204"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)</title>
        <time_frame>Baseline to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Statin and/or Angiotensin Receptor Blocker</title>
            <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily&#xD;
Simvastatin: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors&#xD;
Losartan: Angiotensin II receptor antagonist</description>
          </group>
          <group group_id="O2">
            <title>Usual Treatment</title>
            <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="66"/>
                    <measurement group_id="O2" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Low Density Lipoprotein Levels</title>
        <description>Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c</description>
        <time_frame>Baseline to 12 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Statin and/or Angiotensin Receptor Blocker</title>
            <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily&#xD;
Simvastatin: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors&#xD;
Losartan: Angiotensin II receptor antagonist</description>
          </group>
          <group group_id="O2">
            <title>Usual Treatment</title>
            <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Low Density Lipoprotein Levels</title>
          <description>Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c</description>
          <units>mg/dL</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="99"/>
                <count group_id="O2" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100" lower_limit="96" upper_limit="105"/>
                    <measurement group_id="O2" value="106" lower_limit="101" upper_limit="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>12 months</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="86" lower_limit="82" upper_limit="96"/>
                    <measurement group_id="O2" value="100" lower_limit="97" upper_limit="117"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Modified Framingham Score as a Summary Cardiovascular Risk Level</title>
        <description>The outcome here is the difference in summary risk level changes (e.g., modified Framingham score) between our two study groups, i.e., do intervention subjects experience differential changes in cardiovascular risk levels compared to control subjects. This outcome will be continuously measured (but not necessarily normally distributed).</description>
        <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Number of Distinct Cardiovascular Prevention Drugs Taken</title>
        <description>Similar to primary outcome measure, but here we count the number of distinct cardiovascular prevention drugs taken by the patient as a continuous measure to reflect potential for partial treatment.</description>
        <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Systolic Blood Pressure</title>
        <description>Similar to secondary outcome measure but focusing on Systolic Blood Pressure</description>
        <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Hemoglobin A1C</title>
        <description>Similar to secondary outcome measure but focusing on Hemoglobin A1c</description>
        <time_frame>Baseline and 3, 6, 9, and 12 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Percent on Adequate Cardiovascular Prevention Care</title>
        <time_frame>Baseline to 3 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Percent on Adequate Cardiovascular Prevention Care</title>
        <time_frame>Baseline to 6 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Change in Percent on Adequate Cardiovascular Prevention Care</title>
        <time_frame>Baseline to 9 months</time_frame>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Mean Percentage of Follow up Time During Which Each Group is on Adequate Cardiovascular Prevention Care</title>
        <time_frame>Baseline to 12 months</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years per participant</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Statin and/or Angiotensin Receptor Blocker</title>
          <description>Simvastatin 20mg PO daily and/or Losartan 25mg PO daily&#xD;
Simvastatin: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors&#xD;
Losartan: Angiotensin II receptor antagonist</description>
        </group>
        <group group_id="E2">
          <title>Usual Treatment</title>
          <description>We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize &quot;usual treatment&quot;. We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Elevated creatine kinase level</sub_title>
                <description>Classified as severe if &gt;2x normal range</description>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Leukemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes</sub_title>
                <description>New onset</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Placed on Lithium while on Losartan</sub_title>
                <description>This is a relative contraindication. Patient taken off of losartan when team informed going on lithium. No sequelae</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Completed suicide</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>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="72" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="50" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Medical Hospitalization</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Laboratory values outside normal range</sub_title>
                <counts group_id="E1" subjects_affected="43" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric Hospitalization</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="99"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Dost Ongur</name_or_title>
      <organization>McLean Hospital</organization>
      <phone>617 855 3922</phone>
      <email>dongur@partners.org</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/NCT02188121
org study id: 2014P001599
nct id: NCT02188121
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
Patients with severe mental illness (SMI) die younger than persons in the general population.
      Much of the excess mortality for SMI patients is attributable to cardiovascular disease, and
      is exacerbated by treatment with second-generation antipsychotics (2GAs). Although the
      cardiovascular risks are well-known, and safe, efficacious therapy exists, few SMI patients
      receive cardiovascular prevention drugs. Care delivery fragmentation and poor patient
      adherence are central problems to reducing cardiovascular risks for patients with SMI. To
      address these problems, we propose to conduct a multi-site, open-label, randomized controlled
      trial comparing an initial treatment strategy of free, fixed-doses of two generic,
      cardiovascular prevention drugs (statins and angiotensin drugs) delivered within mental
      health clinics versus usual treatment. The study will include adult patients (18+ years old)
      with schizophrenia, schizoaffective disorder, bipolar disorder, major depressive disorder, or
      psychosis not otherwise specified (NOS) who have received 2GAs treatment within the past six
      months from within four mental health clinics in the Boston area. We have three aims: 1) to
      compare the proportions of subjects in each arm who are receiving cardiovascular drug
      treatment and are adherent to therapy during 12-months of follow-up; 2) to compare changes in
      composite (e.g., Framingham scores) and individual (e.g., lipid levels) cardiovascular risk
      factor levels using an intent-to-treat (ITT) approach; and 3) to compare risk factor levels,
      accounting for variation in adherence over time, using causal inference techniques to
      estimate the per-protocol effect of the intervention. Our three aims examine whether this low
      cost, streamlined treatment strategy increases the numbers of subjects receiving
      cardiovascular prevention therapy and improves cardiovascular risk levels. We will follow
      subjects for 12 months, and collect interview and biometric data at baseline and over the
      following 12 months. Subjects will have the option to continue for another 12 months, during
      which we will continue to collect interview and biometric data, but will not prescribe
      cardiovascular medications. This population-based initial treatment strategy could be an
      effective and efficient approach for overcoming traditional barriers to cardiovascular
      disease prevention within the SMI population. Findings from this study will inform efforts to
      improve care and outcomes, and to enhance survival for patients with severe mental illness.
By design, all subjects in the Intervention arm will start by being under treatment. During
      the course of follow-up, we expect that some will stay consistently on treatment, some will
      discontinue treatment (become non-adherent), while others will make transitions on and off
      treatment in various patterns. In contrast, by design, subjects in the Usual Treatment
      (control) arm do not start on treatment; however, some will initiate treatment as a result of
      usual clinical care, e.g., primary care physician initiation. At any point we will be
      comparing two binary outcomes (on or off treatment) and will use standard methods for
      comparing two proportions to test statistical significance and get confidence intervals for
      the difference in the percent on treatment in the two arms. Participants who are ineligible
      for randomization will be followed similarly to participants in the Usual Treatment Arm, in a
      third, non-randomized group, which will be excluded from the primary analysis.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants on Adequate Cardiovascular Prevention Care (Defined as Taking a Statin and Angiotensin Medication)
time frame: Baseline to 12 months
measure: Change in Low Density Lipoprotein Levels
time frame: Baseline to 12 months
description: Similar to secondary outcome measure but focusing on Low Density Lipoprotein, Systolic Blood Pressure, and Hemoglobin A1c
measure: Change in Modified Framingham Score as a Summary Cardiovascular Risk Level
time frame: Baseline and 3, 6, 9, and 12 months
description: The outcome here is the difference in summary risk level changes (e.g., modified Framingham score) between our two study groups, i.e., do intervention subjects experience differential changes in cardiovascular risk levels compared to control subjects. This outcome will be continuously measured (but not necessarily normally distributed).
measure: Change in Number of Distinct Cardiovascular Prevention Drugs Taken
time frame: Baseline and 3, 6, 9, and 12 months
description: Similar to primary outcome measure, but here we count the number of distinct cardiovascular prevention drugs taken by the patient as a continuous measure to reflect potential for partial treatment.
measure: Change in Systolic Blood Pressure
time frame: Baseline and 3, 6, 9, and 12 months
description: Similar to secondary outcome measure but focusing on Systolic Blood Pressure
measure: Change in Hemoglobin A1C
time frame: Baseline and 3, 6, 9, and 12 months
description: Similar to secondary outcome measure but focusing on Hemoglobin A1c
measure: Change in Percent on Adequate Cardiovascular Prevention Care
time frame: Baseline to 3 months
measure: Change in Percent on Adequate Cardiovascular Prevention Care
time frame: Baseline to 6 months
measure: Change in Percent on Adequate Cardiovascular Prevention Care
time frame: Baseline to 9 months
measure: Mean Percentage of Follow up Time During Which Each Group is on Adequate Cardiovascular Prevention Care
time frame: Baseline to 12 months
arm group label: Statin and/or Angiotensin Receptor Blocker
arm group type: Experimental
description: Simvastatin 20mg PO daily and/or Losartan 25mg PO daily
arm group label: Usual treatment
arm group type: No Intervention
description: We will compare the initial treatment intervention with usual treatment (control arm), with both arms superimposed on a system of regular monitoring base. The investigators will make no effort to alter or influence treatment or use of that treatment for subjects in the control arm. Note that our goal in the Control arm is to characterize "usual treatment". We will not intervene in this care except in emergencies. Some patients who need care for metabolic syndrome may not be receiving it - just as they would if not in our trial.
intervention type: Drug
intervention name: Simvastatin
description: 3-hydroxy-3-methylglutaryl-coenzyme (HMG-CoA) reductase inhibitors
arm group label: Statin and/or Angiotensin Receptor Blocker
intervention type: Drug
intervention name: Losartan
description: Angiotensin II receptor antagonist
arm group label: Statin and/or Angiotensin Receptor Blocker
criteria: 
gender: All
minimum age: 18 Years
maximum age: 89 Years
healthy volunteers: No
last name: Dost Ongur, MD PhD
role: Principal Investigator
affiliation: Mclean Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mclean Hospital
investigator full name: Dost Ongur
investigator title: Chief of Psychotic Disorders Division at McLean Hospital and Associate Professor in Psychiatry at Harvard Medical School
mesh term: Cardiovascular Diseases
mesh term: Schizophrenia
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Bipolar Disorder
mesh term: Psychotic Disorders
mesh term: Mental Disorders
mesh term: Losartan
mesh term: Simvastatin
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 