<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/NCT03022435</url>
  </required_header>
  <id_info>
    <org_study_id>SU-17219-2012</org_study_id>
    <secondary_id>2U19AI057229-06</secondary_id>
    <nct_id>NCT03022435</nct_id>
  </id_info>
  <brief_title>T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 4, 2012</brief_title>
  <official_title>Protective Mechanisms Against a Pandemic Respiratory Virus: B-cell, T-cell, and General Immune Response to Seasonal Influenza Vaccine. Year 4, 2012</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Allergy and Infectious Diseases (NIAID)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Stanford University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will investigate markers, mechanisms and define general predictors for&#xD;
      immunological health by comparing influenza vaccine responses in monozygotic and dizygotic&#xD;
      twins.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to study the response to different influenza vaccines much more&#xD;
      broadly and deeply across different age groups and with different vaccine modalities and to&#xD;
      probe the influence of genetics on these responses using monozygotic and dizygotic twins. On&#xD;
      an investigational basis, the investigators plan to compare various immunological responses,&#xD;
      identify age-specific biomarkers or clusters of markers, quantify the frequency of&#xD;
      influenza-specific T-cells pre- and post-vaccination, and determine the effective breadth of&#xD;
      T-cell repertoire to an influenza vaccine within an individual as a function of age and to&#xD;
      what degree this is genetically determined.&#xD;
&#xD;
      Twin group B will will be randomly assigned to receive a single dose of inactivated vaccine,&#xD;
      either the trivalent inactivated influenza vaccine (TIV) or intranasal live, attenuated&#xD;
      influenza vaccine (LAIV). Twin Groups C-E will receive a single administration of TIV. Group&#xD;
      F, elderly participants, will be randomly assigned to receive a single dose of inactivated&#xD;
      vaccine, either the standard dose or the high-dose TIV. Blood samples to conduct the assays&#xD;
      described will be taken at pre-immunization, Days 7-10 and 28 post-immunization.&#xD;
&#xD;
      Groups A, C and E were not enrolled for this year of the five year annual study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 2012</start_date>
  <completion_date type="Actual">January 2013</completion_date>
  <primary_completion_date type="Actual">January 2013</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants Who Received Influenza Vaccine</measure>
    <time_frame>Day 0</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Related Adverse Events</measure>
    <time_frame>Day 0 to 28 post-immunization</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Group B: 18-30 yo identical twins (LAIV)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants to receive FluMist® LAIV by nasal spray.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: 18-30 yo identical twins (TIV)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants to receive Fluzone® standard TIV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D: 40-64 yo identical twins (TIV)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants to receive Fluzone® standard TIV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group F: 65-100 yo identical twins (TIV)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants to receive Fluzone® standard TIV</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group F: 65-100 yo identical twins (High-Dose TIV)</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants to receive High-Dose Fluzone® standard TIV</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TIV</intervention_name>
    <description>Influenza Virus Vaccine Suspension for Intramuscular Injection</description>
    <arm_group_label>Group B: 18-30 yo identical twins (TIV)</arm_group_label>
    <arm_group_label>Group D: 40-64 yo identical twins (TIV)</arm_group_label>
    <arm_group_label>Group F: 65-100 yo identical twins (TIV)</arm_group_label>
    <other_name>Fluzone® standard TIV</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>High-Dose TIV</intervention_name>
    <description>High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe</description>
    <arm_group_label>Group F: 65-100 yo identical twins (High-Dose TIV)</arm_group_label>
    <other_name>High-Dose Fluzone® TIV</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LAIV</intervention_name>
    <description>Live, attenuated influenza vaccine for Intranasal Spray</description>
    <arm_group_label>Group B: 18-30 yo identical twins (LAIV)</arm_group_label>
    <other_name>FluMist®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Otherwise healthy, ambulatory adults, ages 18-30 years (identical or fraternal twin&#xD;
             pairs), 40-64 years (identical or fraternal twin pairs) or 65-100 years (identical&#xD;
             twin pairs).&#xD;
&#xD;
          2. Willing to complete the informed consent process.&#xD;
&#xD;
          3. Availability for follow-up for the planned duration of the study at least 28 days&#xD;
             after immunization.&#xD;
&#xD;
          4. Acceptable medical history and vital signs.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Prior off-study vaccination with trivalent inactivated influenza vaccine (TIV) or live&#xD;
             attenuated influenza vaccine (LAIV) in Fall 2012&#xD;
&#xD;
          2. Allergy to egg or egg products, or to vaccine components (including gentamicin,&#xD;
             gelatin, arginine or MSG (LAIV for Group B only), and thimerosal (if TIV multidose&#xD;
             vials used)&#xD;
&#xD;
          3. Life-threatening reactions to previous influenza vaccinations&#xD;
&#xD;
          4. Active systemic or serious concurrent illness, including febrile illness the day of&#xD;
             vaccination&#xD;
&#xD;
          5. History of immunodeficiency (including HIV infection)&#xD;
&#xD;
          6. Known or suspected impairment of immunologic function, including, but not limited to,&#xD;
             clinically significant liver disease, diabetes mellitus treated with insulin, moderate&#xD;
             to severe renal disease or any other chronic disorder which, in the opinion of the&#xD;
             investigator, might jeopardize volunteer safety or compliance with the protocol.&#xD;
&#xD;
          7. Blood pressure &gt;150 systolic or &gt; 95 diastolic at Visit 1&#xD;
&#xD;
          8. Hospitalization in the past year for congestive heart failure or emphysema.&#xD;
&#xD;
          9. Chronic Hepatitis B or C&#xD;
&#xD;
         10. Recent or current use of immunosuppressive medication, including glucocorticoids&#xD;
             (corticosteroid nasal sprays, topical steroids and inhaled steroids are permissible).&#xD;
             Use of oral steroids (&lt;20mg prednisone-equivalent/day) may be acceptable after review&#xD;
             by the investigator.&#xD;
&#xD;
         11. Malignancy, other than squamous cell or basal cell skin cancer (includes solid tumors&#xD;
             such as breast cancer or prostate cancer with recurrence in the past year, and any&#xD;
             hematologic cancer such as leukemia).&#xD;
&#xD;
         12. Autoimmune disease (including rheumatoid arthritis treated with immunosuppressive&#xD;
             medication such as Plaquenil, methotrexate, prednisone, Enbrel) which, in the opinion&#xD;
             of the investigator, might jeopardize volunteer safety or compliance with the&#xD;
             protocol.&#xD;
&#xD;
         13. History of blood dyscrasias, renal disease, or hemoglobinopathies requiring regular&#xD;
             medical follow up or hospitalization during the preceding year&#xD;
&#xD;
         14. Use of any anti-coagulation medication such as Coumadin or Lovenox, or anti-platelet&#xD;
             agents such as aspirin (except aspirin up to 325 mg.day), Plavix, or Aggrenox must be&#xD;
             reviewed by investigator to determine if this would affect the volunteer's safety.&#xD;
&#xD;
         15. Receipt of blood or blood products within the past 6 months or planned receipt of&#xD;
             blood products prior to completion of study visits.&#xD;
&#xD;
         16. Medical or psychiatric condition or occupational responsibilities that preclude&#xD;
             participant compliance with the protocol&#xD;
&#xD;
         17. Receipt of inactivated vaccine 14 days prior to study vaccination, or planned&#xD;
             non-study vaccination prior to completion of Visit 03 (~Day 28 after the study&#xD;
             vaccination)&#xD;
&#xD;
         18. Receipt of live, attenuated vaccine within 60 days of vaccination, or planned&#xD;
             non-study vaccination prior to completion of Visit 03 (~Day 28 after the study&#xD;
             vaccination)&#xD;
&#xD;
         19. Need for allergy immunization (that cannot be postponed) during the study period V01&#xD;
             to V03 (~Day 28)&#xD;
&#xD;
         20. History of Guillain-Barre Syndrome&#xD;
&#xD;
         21. Pregnant or lactating woman&#xD;
&#xD;
         22. Use of investigational agents within 30 days prior to enrollment or planned use of&#xD;
             investigational agents prior to completion of study visits.&#xD;
&#xD;
         23. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment or&#xD;
             planned blood donation prior to completion of Visit 03 ( ~28 Day after study&#xD;
             vaccination)&#xD;
&#xD;
         24. A current member of the clinical study team.&#xD;
&#xD;
         25. Any condition which, in the opinion of the investigator, might interfere with&#xD;
             volunteer safety, study objectives or the ability of the participant to understand or&#xD;
             comply with the study protocol.&#xD;
&#xD;
         26. Asthma or history of wheezing (for Group B volunteers only)&#xD;
&#xD;
         27. Participants in close contact with anyone who has a severely weakened immune system&#xD;
             should not receive LAIV (for Group B volunteers only)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Cornelia Dekker, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Mark Davis, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Garry Nolan, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ann Arvin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Stephen Quake, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Stanford University</affiliation>
  </overall_official>
  <reference>
    <citation>Kay AW, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Holmes S, Blish CA. Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy. Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14506-11. doi: 10.1073/pnas.1416569111. Epub 2014 Sep 22.</citation>
    <PMID>25246558</PMID>
  </reference>
  <reference>
    <citation>O'Gorman WE, Huang H, Wei YL, Davis KL, Leipold MD, Bendall SC, Kidd BA, Dekker CL, Maecker HT, Chien YH, Davis MM. The Split Virus Influenza Vaccine rapidly activates immune cells through Fcgamma receptors. Vaccine. 2014 Oct 14;32(45):5989-97. doi: 10.1016/j.vaccine.2014.07.115. Epub 2014 Sep 6.</citation>
    <PMID>25203448</PMID>
  </reference>
  <reference>
    <citation>Kay AW, Bayless NL, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Blish CA. Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. J Infect Dis. 2015 Sep 15;212(6):861-70. doi: 10.1093/infdis/jiv138. Epub 2015 Mar 4.</citation>
    <PMID>25740957</PMID>
  </reference>
  <verification_date>May 2017</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 16, 2017</study_first_posted>
  <results_first_submitted>January 17, 2017</results_first_submitted>
  <results_first_submitted_qc>January 17, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">March 9, 2017</results_first_posted>
  <last_update_submitted>May 18, 2017</last_update_submitted>
  <last_update_submitted_qc>May 18, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 22, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Stanford University</investigator_affiliation>
    <investigator_full_name>Cornelia L. Dekker</investigator_full_name>
    <investigator_title>Professor, Pediatrics</investigator_title>
  </responsible_party>
  <keyword>Inactivated influenza vaccine</keyword>
  <keyword>Live, attenuated influenza vaccine</keyword>
  <keyword>Adult and elderly identical twins</keyword>
  <keyword>Adult fraternal twins</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Numbers listed in the tables reflect individual twins and not twin pairs.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Group B: 18-30 yo Identical Twins (LAIV)</title>
          <description>Participants to receive FluMist® LAIV by nasal spray.</description>
        </group>
        <group group_id="P2">
          <title>Group B: 18-30 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="P3">
          <title>Group D: 40 - 64 yo Identical Twins</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="P4">
          <title>Group F: 65-100 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="P5">
          <title>Group F: 65-100 yo Identical Twins (High-Dose TIV)</title>
          <description>Participants to receive High-Dose Fluzone® standard TIV</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group B: 18-30 yo Identical Twins (LAIV)</title>
          <description>Participants to receive FluMist® LAIV by nasal spray.</description>
        </group>
        <group group_id="B2">
          <title>Group B: 18-30 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="B3">
          <title>Group D: 40 - 64 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="B4">
          <title>Group F: 65 - 100 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="B5">
          <title>Group F: 65 - 100 yo Identical Twins (High-Dose TIV)</title>
          <description>Participants to receive High-Dose Fluzone® standard TIV</description>
        </group>
        <group group_id="B6">
          <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="5"/>
            <count group_id="B2" value="5"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="3"/>
            <count group_id="B5" value="3"/>
            <count group_id="B6" value="22"/>
          </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="22.98" spread="4.26"/>
                    <measurement group_id="B2" value="22.98" spread="4.26"/>
                    <measurement group_id="B3" value="42.76" spread="1.93"/>
                    <measurement group_id="B4" value="73.45" spread="4.20"/>
                    <measurement group_id="B5" value="73.45" spread="4.20"/>
                    <measurement group_id="B6" value="42.14" spread="21.63"/>
                  </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="4"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="6"/>
                  </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="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" 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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </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="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants Who Received Influenza Vaccine</title>
        <time_frame>Day 0</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group B: 18-30 yo Identical Twins (LAIV)</title>
            <description>Participants to receive FluMist® LAIV by nasal spray.</description>
          </group>
          <group group_id="O2">
            <title>Group B: 18-30 yo Identical Twins (TIV)</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O3">
            <title>Group D: 40 - 64 yo Identical Twins (TIV)</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O4">
            <title>Group F: 65 - 100 yo Identical Twins (TIV)</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O5">
            <title>Group F: 65 - 100 yo Identical Twins (High-Dose TIV)</title>
            <description>Participants to receive High-Dose Fluzone® standard TIV</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Received Influenza Vaccine</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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Related Adverse Events</title>
        <time_frame>Day 0 to 28 post-immunization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group B: 18-30 yo Identical Twins (LAIV)</title>
            <description>Participants to receive FluMist® LAIV by nasal spray</description>
          </group>
          <group group_id="O2">
            <title>Group B: 18-30 yo Identical Twins (TIV)</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O3">
            <title>Group D: 40 - 64 yo Identical Twins</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O4">
            <title>Group F: 65 - 100 yo Identical Twins (TIV)</title>
            <description>Participants to receive Fluzone® standard TIV</description>
          </group>
          <group group_id="O5">
            <title>Group F: 65 - 100 yo Identical Twins (High Dose TIV)</title>
            <description>Participants to receive High-Dose Fluzone® standardTIV</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Related Adverse Events</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="5"/>
                <count group_id="O2" value="5"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="3"/>
                <count group_id="O5" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 0 to 28 of study participation</time_frame>
      <desc>Clinical assessment performed at each visit</desc>
      <group_list>
        <group group_id="E1">
          <title>Group B: 18-30 yo Identical Twins (LAIV)</title>
          <description>Participants to receive FluMist® LAIV by nasal spray.</description>
        </group>
        <group group_id="E2">
          <title>Group B: 18-30 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="E3">
          <title>Group D: 40 - 64 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="E4">
          <title>Group F: 65 - 100 yo Identical Twins (TIV)</title>
          <description>Participants to receive Fluzone® standard TIV</description>
        </group>
        <group group_id="E5">
          <title>Group F: 65 - 100 yo Identical Twins (High-Dose TIV)</title>
          <description>Participants to receive High-Dose Fluzone® standard TIV</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="5"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="3"/>
              </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. Cornelia Dekker.</name_or_title>
      <organization>Stanford University School of Medicine, Dept. of Pediatrics</organization>
      <phone>650-724-4437</phone>
      <email>cdekker@stanford.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/NCT03022435
org study id: SU-17219-2012
secondary id: 2U19AI057229-06
nct id: NCT03022435
lead sponsor: 
collaborator: 
has dmc: No
This study will investigate markers, mechanisms and define general predictors for
      immunological health by comparing influenza vaccine responses in monozygotic and dizygotic
      twins.
The investigators plan to study the response to different influenza vaccines much more
      broadly and deeply across different age groups and with different vaccine modalities and to
      probe the influence of genetics on these responses using monozygotic and dizygotic twins. On
      an investigational basis, the investigators plan to compare various immunological responses,
      identify age-specific biomarkers or clusters of markers, quantify the frequency of
      influenza-specific T-cells pre- and post-vaccination, and determine the effective breadth of
      T-cell repertoire to an influenza vaccine within an individual as a function of age and to
      what degree this is genetically determined.

      Twin group B will will be randomly assigned to receive a single dose of inactivated vaccine,
      either the trivalent inactivated influenza vaccine (TIV) or intranasal live, attenuated
      influenza vaccine (LAIV). Twin Groups C-E will receive a single administration of TIV. Group
      F, elderly participants, will be randomly assigned to receive a single dose of inactivated
      vaccine, either the standard dose or the high-dose TIV. Blood samples to conduct the assays
      described will be taken at pre-immunization, Days 7-10 and 28 post-immunization.

      Groups A, C and E were not enrolled for this year of the five year annual study.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Number of Participants Who Received Influenza Vaccine
time frame: Day 0
measure: Number of Participants With Related Adverse Events
time frame: Day 0 to 28 post-immunization
arm group label: Group B: 18-30 yo identical twins (LAIV)
arm group type: Other
description: Participants to receive FluMist® LAIV by nasal spray.
arm group label: Group B: 18-30 yo identical twins (TIV)
arm group type: Other
description: Participants to receive Fluzone® standard TIV
arm group label: Group D: 40-64 yo identical twins (TIV)
arm group type: Other
description: Participants to receive Fluzone® standard TIV
arm group label: Group F: 65-100 yo identical twins (TIV)
arm group type: Other
description: Participants to receive Fluzone® standard TIV
arm group label: Group F: 65-100 yo identical twins (High-Dose TIV)
arm group type: Other
description: Participants to receive High-Dose Fluzone® standard TIV
intervention type: Biological
intervention name: TIV
description: Influenza Virus Vaccine Suspension for Intramuscular Injection
arm group label: Group B: 18-30 yo identical twins (TIV)
arm group label: Group D: 40-64 yo identical twins (TIV)
arm group label: Group F: 65-100 yo identical twins (TIV)
other name: Fluzone® standard TIV
intervention type: Biological
intervention name: High-Dose TIV
description: High-Dose Influenza Virus Vaccine supplied in a prefilled, single-dose syringe
arm group label: Group F: 65-100 yo identical twins (High-Dose TIV)
other name: High-Dose Fluzone® TIV
intervention type: Biological
intervention name: LAIV
description: Live, attenuated influenza vaccine for Intranasal Spray
arm group label: Group B: 18-30 yo identical twins (LAIV)
other name: FluMist®
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Cornelia Dekker, MD
role: Principal Investigator
affiliation: Stanford University
last name: Mark Davis, PhD
role: Principal Investigator
affiliation: Stanford University
last name: Garry Nolan, PhD
role: Principal Investigator
affiliation: Stanford University
last name: Ann Arvin, MD
role: Principal Investigator
affiliation: Stanford University
last name: Stephen Quake, PhD
role: Principal Investigator
affiliation: Stanford University
citation: Kay AW, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Holmes S, Blish CA. Enhanced natural killer-cell and T-cell responses to influenza A virus during pregnancy. Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):14506-11. doi: 10.1073/pnas.1416569111. Epub 2014 Sep 22.
PMID: 25246558
citation: O'Gorman WE, Huang H, Wei YL, Davis KL, Leipold MD, Bendall SC, Kidd BA, Dekker CL, Maecker HT, Chien YH, Davis MM. The Split Virus Influenza Vaccine rapidly activates immune cells through Fcgamma receptors. Vaccine. 2014 Oct 14;32(45):5989-97. doi: 10.1016/j.vaccine.2014.07.115. Epub 2014 Sep 6.
PMID: 25203448
citation: Kay AW, Bayless NL, Fukuyama J, Aziz N, Dekker CL, Mackey S, Swan GE, Davis MM, Blish CA. Pregnancy Does Not Attenuate the Antibody or Plasmablast Response to Inactivated Influenza Vaccine. J Infect Dis. 2015 Sep 15;212(6):861-70. doi: 10.1093/infdis/jiv138. Epub 2015 Mar 4.
PMID: 25740957
responsible party type: Principal Investigator
investigator affiliation: Stanford University
investigator full name: Cornelia L. Dekker
investigator title: Professor, Pediatrics
mesh term: Influenza, Human
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 