<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/NCT03272711</url>
  </required_header>
  <id_info>
    <org_study_id>201509107</org_study_id>
    <nct_id>NCT03272711</nct_id>
  </id_info>
  <brief_title>Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training</brief_title>
  <acronym>BBS</acronym>
  <official_title>Remediation of Age-related Cognitive Decline: Vortioxetine and Cognitive Training</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Washington University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Queen's University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Takeda</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Washington University School of Medicine</source>
  <oversight_info>
    <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>
      The purpose of this research study is to examine the potential benefits of vortioxetine in&#xD;
      combination with at-home computerized cognitive training program to improve cognition, such&#xD;
      as memory, attention, and concentration. This study will compare the effectiveness of&#xD;
      vortioxetine plus cognitive training versus placebo plus cognitive training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this research study is to examine the potential benefits of vortioxetine in&#xD;
      combination with at-home computerized cognitive training program to improve cognition, such&#xD;
      as memory, attention, and concentration. This study will compare the effectiveness of&#xD;
      vortioxetine plus cognitive training versus placebo plus cognitive training.&#xD;
&#xD;
      Vortioxetine is considered investigational when used as a treatment for age-related cognitive&#xD;
      decline, which means that it has not been approved by the U.S. Food and Drug Administration&#xD;
      for this purpose. Vortioxetine is approved by the U.S. Food and Drug Administration as a&#xD;
      treatment for depression, and also goes by the name Trintellix (formerly known as&#xD;
      Brintellix). That means that, while the drug itself is approved by the FDA, it is not&#xD;
      approved for the reasons the investigators are using it in this study.&#xD;
&#xD;
      Participation in this study entails an estimated 6 study visits over the course of&#xD;
      approximately six months. Participants will complete various assessments at our lab at the&#xD;
      Washington University School of Medicine along with check-in visits in-person or over the&#xD;
      phone. Additionally, they will participate in at home computerized cognitive training for&#xD;
      approximately six months, supplemented with either vortioxetine or placebo.&#xD;
&#xD;
      The investigators will assess memory and problem-solving abilities using paper and pencil,&#xD;
      computerized measures, and self-assessments of how participants feel. These tests could&#xD;
      include numbers, letters, symbols, words, or sentences. These tests will be repeated&#xD;
      throughout the study. If eligible to do so, participants will complete a baseline MRI scan.&#xD;
&#xD;
      A subset of participants who completed a baseline MRI scan will complete another MRI scan&#xD;
      after approximately 26 weeks of vortioxetine or placebo and at home computerized cognitive&#xD;
      training.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 31, 2016</start_date>
  <completion_date type="Actual">January 24, 2019</completion_date>
  <primary_completion_date type="Actual">January 24, 2019</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Total Fluid Cognitive Score</measure>
    <time_frame>Randomization (0 weeks), 4 weeks</time_frame>
    <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Total Fluid Cognitive Score</measure>
    <time_frame>Randomization (0 weeks), 4 week, 12 week, 26 week</time_frame>
    <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participant Function</measure>
    <time_frame>Randomization (0 weeks), 26 weeks</time_frame>
    <description>Participant function assessed using the UCSD Performance-Based Skills Assessment (UPSA).&#xD;
A validated test that required participants to demonstrate their competence to perform everyday functioning tasks in domains such as comprehension, planning, finances, transportation and communication. A higher scores indicates a better outcome. Scores can range from a minimum of 0 to a maximum of 100.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">129</enrollment>
  <condition>Age-related Cognitive Decline</condition>
  <arm_group>
    <arm_group_label>Vortioxetine plus cognitive training</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo plus cognitive training</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vortioxetine 10 mg</intervention_name>
    <arm_group_label>Vortioxetine plus cognitive training</arm_group_label>
    <other_name>Trintellix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Cognitive training program</intervention_name>
    <description>Online training program, 30 minutes a day, 5 times a week</description>
    <arm_group_label>Placebo plus cognitive training</arm_group_label>
    <arm_group_label>Vortioxetine plus cognitive training</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Community-living men and women age 65 and older&#xD;
&#xD;
          -  Age-related cognitive decline as defined by (a) self-reported cognitive dysfunction&#xD;
             that is attributed to the aging process (in response to screening questions to the&#xD;
             participant); (b) ability to complete cognitive battery, but still scoring less than 1&#xD;
             standard deviation above age-matched norms at both baseline and after the two-week&#xD;
             cognitive training lead-in.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known dementia or other clinical neurodegenerative illness (e.g., Parkinson's disease,&#xD;
             cerebrovascular disease) per self-report, informant report, medical records, or&#xD;
             neuropsychological testing&#xD;
&#xD;
          -  Any current psychiatric disorder&#xD;
&#xD;
          -  Medical conditions that suggest shortened lifespan, such as metastatic cancer; or&#xD;
             would prohibit safe participation in the interventions, including cardiovascular&#xD;
             disease or musculoskeletal conditions; or with the assessments.&#xD;
&#xD;
          -  Sensory impairment that would prevent participation&#xD;
&#xD;
          -  IQ &lt; 70 as estimated by the Wechsler Test of Adult Reading&#xD;
&#xD;
          -  Alcohol or substance abuse within 6 months&#xD;
&#xD;
          -  Concurrent cognitive training, such as brain-training software, or other interventions&#xD;
             expected to affect neuroplasticity&#xD;
&#xD;
          -  Psychotropic medications or those with likely CNS effects (none within 4 weeks prior&#xD;
             to study entry)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Eric Lenze, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Washington University School of Medicine</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL; Advanced Cognitive Training for Independent and Vital Elderly Study Group. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2271-81. doi: 10.1001/jama.288.18.2271.</citation>
    <PMID>12425704</PMID>
  </reference>
  <reference>
    <citation>Bowie CR, Gupta M, Holshausen K, Jokic R, Best M, Milev R. Cognitive remediation for treatment-resistant depression: effects on cognition and functioning and the role of online homework. J Nerv Ment Dis. 2013 Aug;201(8):680-5. doi: 10.1097/NMD.0b013e31829c5030.</citation>
    <PMID>23896849</PMID>
  </reference>
  <reference>
    <citation>Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med. 2013 Mar 28;368(13):1169-71. doi: 10.1056/NEJMp1302513. Epub 2013 Mar 13. No abstract available.</citation>
    <PMID>23484795</PMID>
  </reference>
  <reference>
    <citation>Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.</citation>
    <PMID>25405755</PMID>
  </reference>
  <verification_date>December 2019</verification_date>
  <study_first_submitted>September 1, 2017</study_first_submitted>
  <study_first_submitted_qc>September 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <results_first_submitted>December 2, 2019</results_first_submitted>
  <results_first_submitted_qc>December 27, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">January 14, 2020</results_first_posted>
  <last_update_submitted>December 27, 2019</last_update_submitted>
  <last_update_submitted_qc>December 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 14, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vortioxetine</keyword>
  <keyword>Elderly</keyword>
  <keyword>Online cognitive training</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vortioxetine</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>September 23, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/11/NCT03272711/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Twenty-nine participants were not assigned to a group. Twenty did not meet eligibility criteria for randomization, 8 individuals declined to participate further and one person was a pilot participant.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Vortioxetine Plus Cognitive Training</title>
          <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
        </group>
        <group group_id="P2">
          <title>Placebo Plus Cognitive Training</title>
          <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="49"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="44"/>
                <participants group_id="P2" count="41"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Vortioxetine Plus Cognitive Training</title>
          <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
        </group>
        <group group_id="B2">
          <title>Placebo Plus Cognitive Training</title>
          <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</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="51"/>
            <count group_id="B2" value="49"/>
            <count group_id="B3" value="100"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71.68" spread="4.77"/>
                    <measurement group_id="B2" value="71.88" spread="5.3"/>
                    <measurement group_id="B3" value="71.78" spread="5.01"/>
                  </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="28"/>
                    <measurement group_id="B2" value="23"/>
                    <measurement group_id="B3" value="51"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="49"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="50"/>
                    <measurement group_id="B2" value="48"/>
                    <measurement group_id="B3" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="40"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="78"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Years of Schooling</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="16.80" spread="2.48"/>
                    <measurement group_id="B2" value="16.63" spread="3.24"/>
                    <measurement group_id="B3" value="16.72" spread="2.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Total Fluid Cognitive Score</title>
        <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
        <time_frame>Randomization (0 weeks), 4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vortioxetine Plus Cognitive Training</title>
            <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
          <group group_id="O2">
            <title>Placebo Plus Cognitive Training</title>
            <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Fluid Cognitive Score</title>
          <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in Total Fluid Cognitive Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.14" spread="7.80"/>
                    <measurement group_id="O2" value="3.71" spread="7.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4 Total Fluid Cogntive Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.06" spread="17.06"/>
                    <measurement group_id="O2" value="105.85" spread="12.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Total Fluid Cognitive Score</title>
        <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
        <time_frame>Randomization (0 weeks), 4 week, 12 week, 26 week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vortioxetine Plus Cognitive Training</title>
            <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
          <group group_id="O2">
            <title>Placebo Plus Cognitive Training</title>
            <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Total Fluid Cognitive Score</title>
          <description>Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured &quot;fluid&quot; cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.14" spread="7.8"/>
                    <measurement group_id="O2" value="3.71" spread="7.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.24" spread="7.82"/>
                    <measurement group_id="O2" value="3.93" spread="6.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Week 26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.55" spread="7.95"/>
                    <measurement group_id="O2" value="6.05" spread="8.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Fluid Cognitive Score at Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.06" spread="17.06"/>
                    <measurement group_id="O2" value="105.85" spread="12.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Fluid Cognitive Score at Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="108.12" spread="16.34"/>
                    <measurement group_id="O2" value="105.57" spread="12.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total Fluid Cognitive Score at Week 26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="106.98" spread="17.19"/>
                    <measurement group_id="O2" value="107.51" spread="11.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participant Function</title>
        <description>Participant function assessed using the UCSD Performance-Based Skills Assessment (UPSA).&#xD;
A validated test that required participants to demonstrate their competence to perform everyday functioning tasks in domains such as comprehension, planning, finances, transportation and communication. A higher scores indicates a better outcome. Scores can range from a minimum of 0 to a maximum of 100.</description>
        <time_frame>Randomization (0 weeks), 26 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Vortioxetine Plus Cognitive Training</title>
            <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
          <group group_id="O2">
            <title>Placebo Plus Cognitive Training</title>
            <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
          </group>
        </group_list>
        <measure>
          <title>Participant Function</title>
          <description>Participant function assessed using the UCSD Performance-Based Skills Assessment (UPSA).&#xD;
A validated test that required participants to demonstrate their competence to perform everyday functioning tasks in domains such as comprehension, planning, finances, transportation and communication. A higher scores indicates a better outcome. Scores can range from a minimum of 0 to a maximum of 100.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="49"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change in UPSA Score</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.91" spread="7.26"/>
                    <measurement group_id="O2" value="1.66" spread="8.73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total UPSA Score at Week 26</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.50" spread="8.80"/>
                    <measurement group_id="O2" value="82.44" spread="8.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>26 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Vortioxetine Plus Cognitive Training</title>
          <description>Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Vortioxetine 10 mg&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
        </group>
        <group group_id="E2">
          <title>Placebo Plus Cognitive Training</title>
          <description>Placebo plus cognitive training 5 times weekly for 30 minutes a day&#xD;
Cognitive training program: Online training program, 30 minutes a day, 5 times a week</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Worsening of Coronary Artery Disease</sub_title>
                <description>Hospitalization post bypass surgery</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Hospitalization for Bacterial Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</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="31" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>viral illness</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Musculoskeletal aches</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
              </event>
              <event>
                <sub_title>Dental infectkons/aches</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rashes or pruritis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
              </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. Eric Lenze</name_or_title>
      <organization>Washington University School of Medicine</organization>
      <phone>314-362-1671</phone>
      <email>lenzee@wustl.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03272711
org study id: 201509107
nct id: NCT03272711
lead sponsor: 
collaborator: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research study is to examine the potential benefits of vortioxetine in
      combination with at-home computerized cognitive training program to improve cognition, such
      as memory, attention, and concentration. This study will compare the effectiveness of
      vortioxetine plus cognitive training versus placebo plus cognitive training.
The purpose of this research study is to examine the potential benefits of vortioxetine in
      combination with at-home computerized cognitive training program to improve cognition, such
      as memory, attention, and concentration. This study will compare the effectiveness of
      vortioxetine plus cognitive training versus placebo plus cognitive training.

      Vortioxetine is considered investigational when used as a treatment for age-related cognitive
      decline, which means that it has not been approved by the U.S. Food and Drug Administration
      for this purpose. Vortioxetine is approved by the U.S. Food and Drug Administration as a
      treatment for depression, and also goes by the name Trintellix (formerly known as
      Brintellix). That means that, while the drug itself is approved by the FDA, it is not
      approved for the reasons the investigators are using it in this study.

      Participation in this study entails an estimated 6 study visits over the course of
      approximately six months. Participants will complete various assessments at our lab at the
      Washington University School of Medicine along with check-in visits in-person or over the
      phone. Additionally, they will participate in at home computerized cognitive training for
      approximately six months, supplemented with either vortioxetine or placebo.

      The investigators will assess memory and problem-solving abilities using paper and pencil,
      computerized measures, and self-assessments of how participants feel. These tests could
      include numbers, letters, symbols, words, or sentences. These tests will be repeated
      throughout the study. If eligible to do so, participants will complete a baseline MRI scan.

      A subset of participants who completed a baseline MRI scan will complete another MRI scan
      after approximately 26 weeks of vortioxetine or placebo and at home computerized cognitive
      training.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Total Fluid Cognitive Score
time frame: Randomization (0 weeks), 4 weeks
description: Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured "fluid" cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.
measure: Change in Total Fluid Cognitive Score
time frame: Randomization (0 weeks), 4 week, 12 week, 26 week
description: Total fluid cognitive score from the NIH Toolbox as well as the speed of cognitive improvement The study utilized five cognitive tests from the NIH Toolbox Cognitive Battery that measured "fluid" cognition-the capacity for new learning and information processing. A higher score indicates indicates better performance on these tests. A total fluid cognitive score at or near 100 indicates ability that is average compared with others nationally. Scores around 115 suggest above-average fluid cognitive ability, while scores around 130 suggest superior ability. Conversely, a score around 85 suggests below-average fluid cognitive ability, and a score in the range of 70 or below suggests significant impairment.
measure: Participant Function
time frame: Randomization (0 weeks), 26 weeks
description: Participant function assessed using the UCSD Performance-Based Skills Assessment (UPSA).
A validated test that required participants to demonstrate their competence to perform everyday functioning tasks in domains such as comprehension, planning, finances, transportation and communication. A higher scores indicates a better outcome. Scores can range from a minimum of 0 to a maximum of 100.
arm group label: Vortioxetine plus cognitive training
arm group type: Experimental
description: Vortioxetine (10 mg) plus cognitive training 5 times weekly for 30 minutes a day
arm group label: Placebo plus cognitive training
arm group type: Placebo Comparator
description: Placebo plus cognitive training 5 times weekly for 30 minutes a day
intervention type: Drug
intervention name: Vortioxetine 10 mg
arm group label: Vortioxetine plus cognitive training
other name: Trintellix
intervention type: Behavioral
intervention name: Cognitive training program
description: Online training program, 30 minutes a day, 5 times a week
arm group label: Placebo plus cognitive training
arm group label: Vortioxetine plus cognitive training
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Eric Lenze, MD
role: Principal Investigator
affiliation: Washington University School of Medicine
facility: 
country: United States
citation: Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL; Advanced Cognitive Training for Independent and Vital Elderly Study Group. Effects of cognitive training interventions with older adults: a randomized controlled trial. JAMA. 2002 Nov 13;288(18):2271-81. doi: 10.1001/jama.288.18.2271.
PMID: 12425704
citation: Bowie CR, Gupta M, Holshausen K, Jokic R, Best M, Milev R. Cognitive remediation for treatment-resistant depression: effects on cognition and functioning and the role of online homework. J Nerv Ment Dis. 2013 Aug;201(8):680-5. doi: 10.1097/NMD.0b013e31829c5030.
PMID: 23896849
citation: Kozauer N, Katz R. Regulatory innovation and drug development for early-stage Alzheimer's disease. N Engl J Med. 2013 Mar 28;368(13):1169-71. doi: 10.1056/NEJMp1302513. Epub 2013 Mar 13. No abstract available.
PMID: 23484795
citation: Lampit A, Hallock H, Valenzuela M. Computerized cognitive training in cognitively healthy older adults: a systematic review and meta-analysis of effect modifiers. PLoS Med. 2014 Nov 18;11(11):e1001756. doi: 10.1371/journal.pmed.1001756. eCollection 2014 Nov.
PMID: 25405755
responsible party type: Sponsor
mesh term: Cognitive Dysfunction
mesh term: Vortioxetine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 