<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/NCT03004040</url>
  </required_header>
  <id_info>
    <org_study_id>Protection from Influenza</org_study_id>
    <nct_id>NCT03004040</nct_id>
  </id_info>
  <brief_title>Protection From Influenza: Determining the Impact of Prior Infection</brief_title>
  <sponsors>
    <lead_sponsor>
      <agency>Health Sciences North Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>NOAMA NORTHERN ONTARIO ACADEMIC MEDICINE ASSOCIATION</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Health Sciences North Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators propose a unique methodology of studying infection and vaccination history&#xD;
      and immune responses. As most studies in infection history are conducted on mice, limitations&#xD;
      are inherent on their applicability to humans. A longitudinal comparison study following&#xD;
      older adults (over the age of 65) hospitalized for influenza are followed through to their&#xD;
      hospital discharge and vaccination in the following season. This will allow for the&#xD;
      investigation of the course of infection, as well as impact on the response to vaccination.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Significance: This study will provide critical information on the best technique in vaccine&#xD;
      candidate testing and improve influenza treatment approaches. The long-term goal of this&#xD;
      research is to identify the T-cell responses that are surrogates (biomarkers) of serious&#xD;
      complications of influenza in older adults and predict vaccine efficacy (prevention of&#xD;
      influenza illness) and vaccine effectiveness (prevention of serious complications). Further,&#xD;
      translating new insights into age-related immune dysfunction to the design of new influenza&#xD;
      vaccines is critical to addressing this unmet need in the population aged 65 and older.&#xD;
&#xD;
      Innovation: The study will help in the validation of clinical tools and biomarkers as&#xD;
      prognostic indicators of influenza illness severity in vaccinated older adults, point-of-care&#xD;
      diagnostics that would direct other preventive strategies to reduce the impact of influenza&#xD;
      illness in vaccinated older adults, and correlates of protection to evaluate the potential of&#xD;
      new influenza vaccines to enhance protection against the serious complications of influenza&#xD;
      illness. The investigators have established that GrzB activity and the IFNg: IL-10 ratio in&#xD;
      influenza-stimulated PBMC correlate with protection against influenza, and preliminary data&#xD;
      to show that low GrzB activity in influenza-stimulated PBMC correlates with more severe&#xD;
      disease and higher levels of frailty. The innovations of this project are the established&#xD;
      methods for developing correlates of protection, the clinical insights into how frailty&#xD;
      affects immune-mediated protection against influenza, and the direct translation of this&#xD;
      research to provide a reasonable method for primary care clinicians to estimate vaccine&#xD;
      effectiveness in an individual older person. These results will translate to the practical&#xD;
      design of clinical trials to evaluate the potential for new influenza vaccines to better&#xD;
      protect against the serious complications of influenza and complement those based on antibody&#xD;
      titers and/or clinical outcomes alone.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date>December 2016</start_date>
  <completion_date type="Anticipated">January 2019</completion_date>
  <primary_completion_date type="Anticipated">January 2019</primary_completion_date>
  <study_type>Observational [Patient Registry]</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <target_duration>1 Year</target_duration>
  <primary_outcome>
    <measure>High expression of CTL associated cytokines and granzymes in PBMC's are predictors of influenza infection severity.</measure>
    <time_frame>2 years</time_frame>
    <description>PBMCs from adults hospitalized for laboratory confirmed influenza illness (LCII) will be collected at admission and 30 days post hospitalization. These samples will be matched with hospitalized non-LCII adult controls. T-cells will be isolated from whole blood samples and gene expression of IFNg, IL10 and GrzB will be measured and compared between time points and subjects. These levels do not have a separate unit of measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vaccination in previously infected individuals increases the protection provided by subsequent vaccination and will be higher than those receiving vaccination alone (with no previous infection)</measure>
    <time_frame>2 years</time_frame>
    <description>Older adults hospitalized for influenza illness the previous season will be compared to matched, hospitalized older adults with influenza-like illness (non-LCII). PBMCs will be collected from each group, before receiving influenza vaccination and 4 weeks after vaccination. PBMCs will be challenged ex vivo with influenza virus and gene expression of CTL related genes will be measured and compared between each group.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Case</arm_group_label>
    <description>older adult patients (over the age of 65) admitted to Health Sciences North with laboratory confirmed influenza illness (LCII)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <description>matched control subjects (non-LCII)</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Flu Vaccine</intervention_name>
    <arm_group_label>Case</arm_group_label>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        Older adult patients (over the age of 65) admitted to Health Sciences North with laboratory&#xD;
        confirmed influenza illness (LCII) and matched control subjects (non-LCII).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent provided by the participant.&#xD;
&#xD;
          2. Age 65 years of age or older admitted to Health Sciences North with at least one the&#xD;
             following:&#xD;
&#xD;
               -  Laboratory confirmed influenza illness&#xD;
&#xD;
               -  Acute exacerbation of chronic obstructive pulmonary disease (AECOPD).&#xD;
&#xD;
               -  Any respiratory or influenza-like symptoms (dyspnea, cough, sore throat, myalgia,&#xD;
                  arthralgia, fever, delirium/altered level of consciousness) that a test for&#xD;
                  influenza was negative.&#xD;
&#xD;
          3. Willing to receive influenza vaccination in the subsequent flu season&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients whose reason for hospital admission was unrelated to influenza or (for&#xD;
             example patients admitted due to trauma, elective surgery, or patients who have an&#xD;
             alternative diagnosis that is clearly not respiratory).&#xD;
&#xD;
          2. Chest x-ray positive for pneumonia.&#xD;
&#xD;
          3. Study participants who cannot be vaccinated due to previous severe reaction to&#xD;
             influenza vaccine, egg, latex, or thimerosol allergies, or refusal of vaccination.&#xD;
&#xD;
          4. Immunosuppressive disorders or medications (including oral prednisone in doses &gt;10 mg&#xD;
             daily).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Amanda Axler, BSc.</last_name>
    <phone>7055237300</phone>
    <phone_ext>1924</phone_ext>
    <email>aaxler@hsnri.ca</email>
  </overall_contact>
  <location>
    <facility>
      <name>Health Sciences North Research Institute</name>
      <address>
        <city>Sudbury</city>
        <state>Ontario</state>
        <zip>P3E 5J1</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Amanda l Axler, BSc</last_name>
      <phone>705-523-7300</phone>
      <phone_ext>1924</phone_ext>
      <email>aaxler@amric.ca</email>
    </contact>
    <contact_backup>
      <last_name>Beth Gentleman, BSc</last_name>
      <phone>705-523-7300</phone>
      <phone_ext>2631</phone_ext>
      <email>bgentleman@amric.ca</email>
    </contact_backup>
    <investigator>
      <last_name>Janet E McElhaney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 22, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>February 22, 2018</last_update_submitted>
  <last_update_submitted_qc>February 22, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 23, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Health Sciences North Research Institute</investigator_affiliation>
    <investigator_full_name>Janet McElhaney</investigator_full_name>
    <investigator_title>Vice President of Research and Scientific Director, HSN Volunteer Association Chair in Healthy Aging, Medical Lead for Seniors Care and Consulting Geriatrician</investigator_title>
  </responsible_party>
  <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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03004040
org study id: Protection from Influenza
nct id: NCT03004040
lead sponsor: 
collaborator: 
has dmc: No
The investigators propose a unique methodology of studying infection and vaccination history
      and immune responses. As most studies in infection history are conducted on mice, limitations
      are inherent on their applicability to humans. A longitudinal comparison study following
      older adults (over the age of 65) hospitalized for influenza are followed through to their
      hospital discharge and vaccination in the following season. This will allow for the
      investigation of the course of infection, as well as impact on the response to vaccination.
Significance: This study will provide critical information on the best technique in vaccine
      candidate testing and improve influenza treatment approaches. The long-term goal of this
      research is to identify the T-cell responses that are surrogates (biomarkers) of serious
      complications of influenza in older adults and predict vaccine efficacy (prevention of
      influenza illness) and vaccine effectiveness (prevention of serious complications). Further,
      translating new insights into age-related immune dysfunction to the design of new influenza
      vaccines is critical to addressing this unmet need in the population aged 65 and older.

      Innovation: The study will help in the validation of clinical tools and biomarkers as
      prognostic indicators of influenza illness severity in vaccinated older adults, point-of-care
      diagnostics that would direct other preventive strategies to reduce the impact of influenza
      illness in vaccinated older adults, and correlates of protection to evaluate the potential of
      new influenza vaccines to enhance protection against the serious complications of influenza
      illness. The investigators have established that GrzB activity and the IFNg: IL-10 ratio in
      influenza-stimulated PBMC correlate with protection against influenza, and preliminary data
      to show that low GrzB activity in influenza-stimulated PBMC correlates with more severe
      disease and higher levels of frailty. The innovations of this project are the established
      methods for developing correlates of protection, the clinical insights into how frailty
      affects immune-mediated protection against influenza, and the direct translation of this
      research to provide a reasonable method for primary care clinicians to estimate vaccine
      effectiveness in an individual older person. These results will translate to the practical
      design of clinical trials to evaluate the potential for new influenza vaccines to better
      protect against the serious complications of influenza and complement those based on antibody
      titers and/or clinical outcomes alone.
observational model: Case-Control
time perspective: Prospective
measure: High expression of CTL associated cytokines and granzymes in PBMC's are predictors of influenza infection severity.
time frame: 2 years
description: PBMCs from adults hospitalized for laboratory confirmed influenza illness (LCII) will be collected at admission and 30 days post hospitalization. These samples will be matched with hospitalized non-LCII adult controls. T-cells will be isolated from whole blood samples and gene expression of IFNg, IL10 and GrzB will be measured and compared between time points and subjects. These levels do not have a separate unit of measure.
measure: Vaccination in previously infected individuals increases the protection provided by subsequent vaccination and will be higher than those receiving vaccination alone (with no previous infection)
time frame: 2 years
description: Older adults hospitalized for influenza illness the previous season will be compared to matched, hospitalized older adults with influenza-like illness (non-LCII). PBMCs will be collected from each group, before receiving influenza vaccination and 4 weeks after vaccination. PBMCs will be challenged ex vivo with influenza virus and gene expression of CTL related genes will be measured and compared between each group.
arm group label: Case
description: older adult patients (over the age of 65) admitted to Health Sciences North with laboratory confirmed influenza illness (LCII)
arm group label: Control
description: matched control subjects (non-LCII)
intervention type: Biological
intervention name: Flu Vaccine
arm group label: Case
arm group label: Control
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Amanda Axler, BSc.
phone: 7055237300
phone ext: 1924
email: aaxler@hsnri.ca
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Health Sciences North Research Institute
investigator full name: Janet McElhaney
investigator title: Vice President of Research and Scientific Director, HSN Volunteer Association Chair in Healthy Aging, Medical Lead for Seniors Care and Consulting Geriatrician
mesh term: Influenza, Human
sharing ipd: No