<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/NCT03022396</url>
  </required_header>
  <id_info>
    <org_study_id>SU-17219-2010</org_study_id>
    <secondary_id>2U19AI057229-06</secondary_id>
    <nct_id>NCT03022396</nct_id>
  </id_info>
  <brief_title>T-cell And General Immune Response to Seasonal Influenza Vaccine (SLVP018) Year 2, 2010</brief_title>
  <official_title>Protective Mechanisms Against a Pandemic Respiratory Virus: B- Cell, T-cell, and General Immune Response to Seasonal Influenza Vaccine. Year 2, 2010</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 response to influenza vaccines in monozygotic and dizygotic twins&#xD;
      of different ages.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators plan to study the response to influenza vaccines much more broadly and&#xD;
      deeply across different age groups and with different vaccine formulations and to probe the&#xD;
      influence of genetics on these responses using monozygotic and dizygotic twins. On an&#xD;
      investigational basis, 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 Groups A-E will receive a single administration of the 2010-2011 formulation of seasonal&#xD;
      trivalent inactivated influenza vaccine (TIV). Group F, elderly monozygotic twin&#xD;
      participants, will be randomly assigned to receive a single dose of inactivated vaccine,&#xD;
      either the usual dose or the High-Dose TIV. Blood samples to conduct the assays described&#xD;
      will be taken at pre-immunization, Days 7-10 and 28 post-immunization. Each twin is counted&#xD;
      as a single participant. All reporting numbers reflect the number of participants, not the&#xD;
      number of twin pairs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2010</start_date>
  <completion_date type="Actual">January 2011</completion_date>
  <primary_completion_date type="Actual">January 2011</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 Individual Twins Who Received Influenza Vaccine</measure>
    <time_frame>Day 0 to 28</time_frame>
    <description>All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Individual Twins With Related Adverse Events</measure>
    <time_frame>Day 0 to 28 post-immunization</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Group A: age 8-17 yo identical twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B: age 18-30 yo identical twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C: age 18-30 yo fraternal twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D: age 40 - 59 yo identical twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group E: age 40 - 59 yo fraternal twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group F: age 70 - 100 yo identical twins</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>High Dose Fluzone® (intramuscular)</intervention_name>
    <description>Licensed seasonal High dose trivalent inactivated influenza</description>
    <arm_group_label>Group F: age 70 - 100 yo identical twins</arm_group_label>
    <other_name>High Dose TIV</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Fluzone® (intramuscular)</intervention_name>
    <description>Licensed seasonal trivalent inactivated influenza</description>
    <arm_group_label>Group A: age 8-17 yo identical twins</arm_group_label>
    <arm_group_label>Group B: age 18-30 yo identical twins</arm_group_label>
    <arm_group_label>Group C: age 18-30 yo fraternal twins</arm_group_label>
    <arm_group_label>Group D: age 40 - 59 yo identical twins</arm_group_label>
    <arm_group_label>Group E: age 40 - 59 yo fraternal twins</arm_group_label>
    <arm_group_label>Group F: age 70 - 100 yo identical twins</arm_group_label>
    <other_name>TIV</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Otherwise healthy, ambulatory children or adults, ages 8-17 years (identical twins),&#xD;
             18-30 years (identical or fraternal twins), 40-59 years (identical or fraternal twins)&#xD;
             or 70-100 years (identical twins).&#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;
          5. All female of childbearing potential, must use an acceptable method of contraception&#xD;
             and not become pregnant for the duration of the study (approximately 1 month or to&#xD;
             completion of Visit 3). (Acceptable contraception includes implants, injectables,&#xD;
             combined oral contraceptives, effective intrauterine devices (IUDs), sexual&#xD;
             abstinence, or a vasectomized partner).&#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 2010&#xD;
&#xD;
          2. Allergy to egg or egg products, or to vaccine components, including thimerosal (if TIV&#xD;
             multidose vials used)&#xD;
&#xD;
          3. Life-threatening reactions to previous influenza vaccinations&#xD;
&#xD;
          4. Active systemic or serious concurrent illness, including febrile illness on the day of&#xD;
             vaccination&#xD;
&#xD;
          5. History of immunodeficiency&#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 and inhaled steroids are permissible). Use of oral&#xD;
             steroids (&lt;20mg prednisone-equivalent/day) may be acceptable after review by the&#xD;
             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, Plavix, Aggrenox must be reviewed by investigator to determine&#xD;
             if this would affect the volunteer's safety.&#xD;
&#xD;
         15. Receipt of blood or blood products within the past 6 months&#xD;
&#xD;
         16. Medical or psychiatric condition or occupational responsibilities that preclude&#xD;
             subject compliance with the protocol&#xD;
&#xD;
         17. Inactivated vaccine 14 days prior to vaccination&#xD;
&#xD;
         18. Live, attenuated vaccine within 60 days of vaccination&#xD;
&#xD;
         19. History of Guillain-Barre Syndrome&#xD;
&#xD;
         20. Pregnant or lactating woman&#xD;
&#xD;
         21. Use of investigational agents within 30 days prior to enrollment&#xD;
&#xD;
         22. Donation of the equivalent of a unit of blood within 6 weeks prior to enrollment&#xD;
&#xD;
         23. 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;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 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>Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, Dekker CL, Mackey S, Maecker H, Swan GE, Davis MM, Norman PJ, Guethlein LA, Desai M, Parham P, Blish CA. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med. 2013 Oct 23;5(208):208ra145. doi: 10.1126/scitranslmed.3006702.</citation>
    <PMID>24154599</PMID>
  </reference>
  <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>Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.</citation>
    <PMID>25594173</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>
  <reference>
    <citation>Rubelt F, Bolen CR, McGuire HM, Vander Heiden JA, Gadala-Maria D, Levin M, Euskirchen GM, Mamedov MR, Swan GE, Dekker CL, Cowell LG, Kleinstein SH, Davis MM. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naive and antigen-experienced cells. Nat Commun. 2016 Mar 23;7:11112. doi: 10.1038/ncomms11112.</citation>
    <PMID>27005435</PMID>
  </reference>
  <reference>
    <citation>Horns F, Vollmers C, Croote D, Mackey SF, Swan GE, Dekker CL, Davis MM, Quake SR. Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching. Elife. 2016 Aug 2;5:e16578. doi: 10.7554/eLife.16578. Erratum In: Elife. 2016 Nov 09;5:</citation>
    <PMID>27481325</PMID>
  </reference>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>January 12, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 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>August 15, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">August 21, 2017</results_first_posted>
  <last_update_submitted>August 15, 2017</last_update_submitted>
  <last_update_submitted_qc>August 15, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 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>Identical twins</keyword>
  <keyword>Fraternal twins</keyword>
  <keyword>High-Dose influenza vaccine</keyword>
  <keyword>Elderly twins</keyword>
  <keyword>Child twins</keyword>
  <keyword>Inactivated influenza vaccine, high-dose</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>All numbers of participants reflect an individual participant, not a twin pair. All enrollment numbers reflect the number of participants, not the number of twin pairs.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Group A: Age 8-17 yo Identical Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="P2">
          <title>Group B: Age 18-30 yo Identical Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="P3">
          <title>Group C: Age 18-30 yo Fraternal Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="P4">
          <title>Group D: Age 40 - 59 yo Identical Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="P5">
          <title>Group E: Age 40 - 59 yo Fraternal Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="P6">
          <title>Group F: Age 70 - 100 yo Identical Twins</title>
          <description>Individual Twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)&#xD;
High Dose Fluzone® (intramuscular): Licensed seasonal High dose trivalent inactivated influenza&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="14"/>
                <participants group_id="P6" count="8"/>
              </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 group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>All numbers reflect the number of individual participants, not the number of twin pairs. Ie, in Group A there were 16 participants who were part of 8 twin pairs.</population>
      <group_list>
        <group group_id="B1">
          <title>Group A: Age 8-17 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B2">
          <title>Group B: Age 18-30 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B3">
          <title>Group C: Age 18-30 yo Fraternal Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B4">
          <title>Group D: Age 40 - 59 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B5">
          <title>Group E: Age 40 - 59 yo Fraternal Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B6">
          <title>Group F: Age 70 - 100 yo Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)&#xD;
High Dose Fluzone® (intramuscular): Licensed seasonal High dose trivalent inactivated influenza&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="B7">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="14"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="20"/>
            <count group_id="B5" value="14"/>
            <count group_id="B6" value="8"/>
            <count group_id="B7" value="82"/>
          </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="13.69" spread="1.88"/>
                    <measurement group_id="B2" value="23.71" spread="3.33"/>
                    <measurement group_id="B3" value="22.65" spread="2.99"/>
                    <measurement group_id="B4" value="53.44" spread="2.25"/>
                    <measurement group_id="B5" value="44.52" spread="1.68"/>
                    <measurement group_id="B6" value="75.51" spread="4.50"/>
                    <measurement group_id="B7" value="37.70" spread="19.94"/>
                  </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="8"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="14"/>
                    <measurement group_id="B5" value="13"/>
                    <measurement group_id="B6" value="2"/>
                    <measurement group_id="B7" value="48"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="6"/>
                    <measurement group_id="B7" value="34"/>
                  </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="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="18"/>
                    <measurement group_id="B5" value="14"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="76"/>
                  </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 group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>The Race is inconsistent in Group D because identical twins self reported differently from each other. One identical twin reported Hispanic and American Indian and the other identical twin said Hispanic and Caucasian.</description>
          <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="1"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="6"/>
                  </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 group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </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="4"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="19"/>
                    <measurement group_id="B5" value="8"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <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="0"/>
                    <measurement group_id="B7" value="1"/>
                  </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="16"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="20"/>
                    <measurement group_id="B5" value="14"/>
                    <measurement group_id="B6" value="8"/>
                    <measurement group_id="B7" value="82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Individual Twins Who Received Influenza Vaccine</title>
        <description>All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.</description>
        <time_frame>Day 0 to 28</time_frame>
        <population>All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.</population>
        <group_list>
          <group group_id="O1">
            <title>Group A: Age 8-17 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O2">
            <title>Group B: Age 18-30 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O3">
            <title>Group C: Age 18-30 yo Fraternal Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O4">
            <title>Group D: Age 40 - 59 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O5">
            <title>Group E: Age 40 - 59 yo Fraternal Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O6">
            <title>Group F: Age 70 - 100 yo Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)&#xD;
High Dose Fluzone® (intramuscular): Licensed seasonal High dose trivalent inactivated influenza&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Individual Twins Who Received Influenza Vaccine</title>
          <description>All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.</description>
          <population>All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="20"/>
                <count group_id="O5" value="14"/>
                <count group_id="O6" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="10"/>
                    <measurement group_id="O4" value="20"/>
                    <measurement group_id="O5" value="14"/>
                    <measurement group_id="O6" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Individual Twins With Related Adverse Events</title>
        <time_frame>Day 0 to 28 post-immunization</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A: Age 8-17 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O2">
            <title>Group B: Age 18-30 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O3">
            <title>Group C: Age 18-30 yo Fraternal Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O4">
            <title>Group D: Age 40 - 59 yo Identical Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O5">
            <title>Group E: Age 40 - 59 yo Fraternal Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
          <group group_id="O6">
            <title>Group F: Age 70 - 100 yo Twins</title>
            <description>Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)&#xD;
High Dose Fluzone® (intramuscular): Licensed seasonal High dose trivalent inactivated influenza&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Individual Twins 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="16"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="20"/>
                <count group_id="O5" value="14"/>
                <count group_id="O6" value="8"/>
              </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 group_id="O6" 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 A: Age 8-17 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="E2">
          <title>Group B: Age 18-30 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="E3">
          <title>Group C: Age 18-30 yo Fraternal Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="E4">
          <title>Group D: Age 40 - 59 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="E5">
          <title>Group E: Age 40 - 59 yo Fraternal Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular)&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
        <group group_id="E6">
          <title>Group F: Age 70 - 100 yo Identical Twins</title>
          <description>Individual twins to receive Fluzone® (intramuscular) or High-Dose Fluzone® (intramuscular)&#xD;
High-Dose Fluzone® (intramuscular): Licensed seasonal High-Dose trivalent inactivated influenza&#xD;
Fluzone® (intramuscular): Licensed seasonal trivalent inactivated influenza</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>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/NCT03022396
org study id: SU-17219-2010
secondary id: 2U19AI057229-06
nct id: NCT03022396
lead sponsor: 
collaborator: 
has dmc: No
This study will investigate response to influenza vaccines in monozygotic and dizygotic twins
      of different ages.
The investigators plan to study the response to influenza vaccines much more broadly and
      deeply across different age groups and with different vaccine formulations and to probe the
      influence of genetics on these responses using monozygotic and dizygotic twins. On an
      investigational basis, 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 Groups A-E will receive a single administration of the 2010-2011 formulation of seasonal
      trivalent inactivated influenza vaccine (TIV). Group F, elderly monozygotic twin
      participants, will be randomly assigned to receive a single dose of inactivated vaccine,
      either the usual 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. Each twin is counted
      as a single participant. All reporting numbers reflect the number of participants, not the
      number of twin pairs.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Number of Individual Twins Who Received Influenza Vaccine
time frame: Day 0 to 28
description: All numbers reported are the number of participants, not the number of twin pairs. Each member of a twin was counted individually as a participant.
measure: Number of Individual Twins With Related Adverse Events
time frame: Day 0 to 28 post-immunization
arm group label: Group A: age 8-17 yo identical twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular)
arm group label: Group B: age 18-30 yo identical twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular)
arm group label: Group C: age 18-30 yo fraternal twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular)
arm group label: Group D: age 40 - 59 yo identical twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular)
arm group label: Group E: age 40 - 59 yo fraternal twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular)
arm group label: Group F: age 70 - 100 yo identical twins
arm group type: Other
description: Individual twins to receive Fluzone® (intramuscular) or High Dose Fluzone® (intramuscular)
intervention type: Biological
intervention name: High Dose Fluzone® (intramuscular)
description: Licensed seasonal High dose trivalent inactivated influenza
arm group label: Group F: age 70 - 100 yo identical twins
other name: High Dose TIV
intervention type: Biological
intervention name: Fluzone® (intramuscular)
description: Licensed seasonal trivalent inactivated influenza
arm group label: Group A: age 8-17 yo identical twins
arm group label: Group B: age 18-30 yo identical twins
arm group label: Group C: age 18-30 yo fraternal twins
arm group label: Group D: age 40 - 59 yo identical twins
arm group label: Group E: age 40 - 59 yo fraternal twins
arm group label: Group F: age 70 - 100 yo identical twins
other name: TIV
criteria: 
gender: All
minimum age: 8 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: Horowitz A, Strauss-Albee DM, Leipold M, Kubo J, Nemat-Gorgani N, Dogan OC, Dekker CL, Mackey S, Maecker H, Swan GE, Davis MM, Norman PJ, Guethlein LA, Desai M, Parham P, Blish CA. Genetic and environmental determinants of human NK cell diversity revealed by mass cytometry. Sci Transl Med. 2013 Oct 23;5(208):208ra145. doi: 10.1126/scitranslmed.3006702.
PMID: 24154599
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: Brodin P, Jojic V, Gao T, Bhattacharya S, Angel CJ, Furman D, Shen-Orr S, Dekker CL, Swan GE, Butte AJ, Maecker HT, Davis MM. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015 Jan 15;160(1-2):37-47. doi: 10.1016/j.cell.2014.12.020.
PMID: 25594173
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
citation: Rubelt F, Bolen CR, McGuire HM, Vander Heiden JA, Gadala-Maria D, Levin M, Euskirchen GM, Mamedov MR, Swan GE, Dekker CL, Cowell LG, Kleinstein SH, Davis MM. Individual heritable differences result in unique cell lymphocyte receptor repertoires of naive and antigen-experienced cells. Nat Commun. 2016 Mar 23;7:11112. doi: 10.1038/ncomms11112.
PMID: 27005435
citation: Horns F, Vollmers C, Croote D, Mackey SF, Swan GE, Dekker CL, Davis MM, Quake SR. Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching. Elife. 2016 Aug 2;5:e16578. doi: 10.7554/eLife.16578. Erratum In: Elife. 2016 Nov 09;5:
PMID: 27481325
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: 