<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/NCT02200276</url>
  </required_header>
  <id_info>
    <org_study_id>NA_00092365</org_study_id>
    <nct_id>NCT02200276</nct_id>
  </id_info>
  <brief_title>Influenza Immunization in Adults Over Age 75</brief_title>
  <official_title>Influenza Immunization in Adults Over Age 75</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Johns Hopkins University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The immune system is the part of the body that protects against infection. The immune system&#xD;
      often doesn't work as effectively as people get older. This research is being done to find&#xD;
      out how the immune systems in older people who are over age 75 respond to influenza vaccine&#xD;
      (flu shot). We also want to find out if chronic cytomegalovirus (CMV) infection, a common&#xD;
      virus infection in older persons affects the immune response in people older than 75 years of&#xD;
      age who receive a flu shot. The Flu Shot is a vaccine approved for the prevention of&#xD;
      influenza (&quot;Flu&quot;) infections and is recommended every year for all persons 50 years and&#xD;
      older. People who are older than 75 years of age are considered healthy or frail may join. A&#xD;
      total of 1025 persons will be participating in this study.&#xD;
&#xD;
      In order to determine if you are qualified for the study, we would ask you to answer a few&#xD;
      questions over the phone that will take approximately 5 minutes. If you qualify and agree to&#xD;
      proceed, you will be asked to come to Johns Hopkins Bayview Medical Center or, if you are&#xD;
      unable to come to Bayview, one of our staff can visit you at your home. During that visit we&#xD;
      obtain consent, review your medical history, and measure your vital signs, walking speed and&#xD;
      grip strength. We will also administer a few brief questionnaires and collect urine and blood&#xD;
      samples. We will then give you the Influenza vaccine for free. 7 days post receiving your&#xD;
      Influenza Vaccine we will collect a small blood sample for further immune system testing.&#xD;
      also, you will be asked to complete a 12-question survey which will assess your symptoms over&#xD;
      the past 7 days (post receiving the Influenza vaccine). Also 4 weeks post receiving your&#xD;
      Influenza vaccine you will be asked to complete a third visit that will include follow up&#xD;
      health questionnaires and an influenza symptoms assessment questionnaire and vital signs. A&#xD;
      third blood draw will be collected (approximately 10 teaspoons) to measure immune responses&#xD;
      to the influenza vaccine. In addition, you will receive your test result (CBC/w/Diff.) from&#xD;
      visit #1. Throughout the influenza study season, we will call you once a week to ask about&#xD;
      your general health and any Flu-like symptoms. These calls will be made throughout the Flu&#xD;
      season which typically lasts through May. If you begin to have any influenza like symptoms at&#xD;
      any time during the study, we ask that you call our office to report these symptoms so that&#xD;
      we may perform vital signs, nasal swab to confirm influenza, and a fourth blood draw to look&#xD;
      at the immune response and protection of influenza vaccine.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Seasonal influenza causes significant morbidity and mortality and is the fourth leading cause&#xD;
      of death for older Americans. Annual immunization with a trivalent inactivated influenza&#xD;
      vaccine (TIV) is recommended for all adults 50 years and older. However, despite improved&#xD;
      vaccination coverage in older adults over time, influenza-related mortality has actually&#xD;
      increased. While many TIV studies indicate its benefit for older adults as a whole, these&#xD;
      studies lacked representation of the older and frail subset of the elderly who suffer over&#xD;
      three-quarters of influenza-related mortality. Our pilot study funded by a Beeson K23 award&#xD;
      showed significant vaccine failures in both antibody response to TIV and clinical protection&#xD;
      in the frail elderly. Our preliminary data also suggest that chronic cytomegalovirus (CMV)&#xD;
      infection as defined by the presence of CMV viral DNA in peripheral monocytes using a highly&#xD;
      sensitive and specific nested PCR-based assay developed in our laboratory, rather than&#xD;
      anti-CMV IgG serology, is associated with poor antibody and T-cell responses to TIV&#xD;
      immunization as well as poor clinical protection. This is likely because anti-CMV IgG&#xD;
      serology, the conventional diagnostic measure for chronic CMV infection, is a crude measure&#xD;
      that merely indicates prior exposure to CMV and does not distinguish chronic (persistent)&#xD;
      from past (resolved) infections. Mechanistically, precipitous immune functional decline has&#xD;
      been observed in those over 75 and chronic CMV infection may contribute significantly to&#xD;
      age-related immune senescent remodeling, termed immunosenescence. In order to improve our&#xD;
      assessment of the effectiveness of TIV immunization and understanding of risk factors and&#xD;
      underlying immune mechanisms that determine vaccine failure in adults over age 75, the frail,&#xD;
      oldest old adult subset, this study is designed to conduct prospective, 4-year TIV&#xD;
      immunization and post-vaccination influenza surveillance in adults over 75 years. We will&#xD;
      first assess chronic CMV infection defined by detectable CMV DNA in peripheral blood&#xD;
      monocytes and frailty status of the study participants and administer the Fluzone High-Dose&#xD;
      TIV vaccine. Influenza-like illness (ILI) cases will be identified through post-vaccination&#xD;
      influenza surveillance as previously done in the Beeson project and respiratory specimens&#xD;
      obtained from ILI cases will be tested using the cutting edge PCR-based IBIS assay which can&#xD;
      accurately subtype influenza and other respiratory viruses in the laboratory of Dr. Charlotte&#xD;
      Gaydos in Division of Infectious Disease, a co-investigator of this project. Strain-specific&#xD;
      antibody responses to TIV immunization will be measured by the standard hemogglutination&#xD;
      inhibition (HI) assay. We will also evaluate T-cell responses to influenza viruses at&#xD;
      baseline and after TIV immunization. Taken together, these studies will provide more accurate&#xD;
      assessment of the clinical effectiveness of TIV immunization in real world geriatric&#xD;
      population over age 75 and its underlying humoral and cell-mediated immune mechanisms.&#xD;
      Moreover, we investigate the role of chronic CMV infection as defined by the presence of CMV&#xD;
      viral DNA in peripheral monocytes as a risk factor for vaccine failure in the elderly over&#xD;
      age 75. Because this oldest old subset is growing most rapidly in numbers and is at greatest&#xD;
      risk for influenza-related morbidity and mortality. The long-term goal of this research is to&#xD;
      strengthen immune protection against influenza for vulnerable older Americans through more&#xD;
      effective and targeted immunization strategies as well as possibly through prevention and&#xD;
      mitigation of chronic CMV infection.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Anticipated">June 2026</completion_date>
  <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Presence of CMV Viral DNA in Peripheral Blood Monocytes</measure>
    <time_frame>At the end of each flu season for the next 4 years</time_frame>
    <description>To assess the role of chronic CMV infection as defined by presence of CMV viral DNA in peripheral monocytes as a risk factor for vaccine failure in this oldest old subset.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Immune Responses to High Dose TIV Immunization</measure>
    <time_frame>At the end of the study-5th year</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Effectiveness of High Dose TIV Immunization</measure>
    <time_frame>At the end of the study, 5th year</time_frame>
    <description>To assess clinical effectiveness of High Dose TIV immunization in real world geriatric population over age 75 through post-vaccination influenza detection</description>
  </other_outcome>
  <other_outcome>
    <measure>Influence of Frailty and Chronic CMV Infection on Vaccine-Induced Influenza Strain-Specific Antibody Titers and T-Cell Responses</measure>
    <time_frame>At the end of the study, 5th year</time_frame>
    <description>To assess potential interaction between chronic CMV infection as defined above and frailty in their impact on antibody and T-cell responses to as well as clinical protection of High Dose TIV immunization in the study population.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">1025</enrollment>
  <condition>Influenza</condition>
  <condition>Immunization</condition>
  <condition>Older Adults</condition>
  <condition>Over Age 75</condition>
  <arm_group>
    <arm_group_label>Influenza Immunization</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Influenza immunization in adults over age 75</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Influenza</intervention_name>
    <arm_group_label>Influenza Immunization</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adults over age 75 years&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Allergies to egg or vaccine&#xD;
&#xD;
          -  Active malignancies&#xD;
&#xD;
          -  On radiation or chemotherapy&#xD;
&#xD;
          -  Active systemic inflammatory diseases including rheumatoid arthritis, Crohn's disease,&#xD;
             and ulcerative colitis&#xD;
&#xD;
          -  Acute exacerbation of chronic cardiopulmonary conditions including decompensated CHF&#xD;
             or COPD&#xD;
&#xD;
          -  Taking oral steroids (such as prednisone) or immune modulating drugs (such as&#xD;
             methotrexate).&#xD;
&#xD;
          -  Lacking the capacity to consent (individuals who do not understand what Flu shot is or&#xD;
             need someone else to decide if s/he should get the Flu shot)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>75 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sean Leng</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Engle Abrams</last_name>
    <phone>410-550-2061</phone>
    <email>eabrams3@jhmi.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Janna Shapiro</last_name>
    <phone>410-550-2061</phone>
    <email>jshapi30@jh.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Johns Hopkins University; JHAAC 5501 Hopkins Bayview Circle, 1B84</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Engle Abrams</last_name>
      <phone>410-550-2061</phone>
      <email>eabrams3@jhmi.edu</email>
    </contact>
    <contact_backup>
      <last_name>Trudymae Agboka, M.S. Biology</last_name>
      <phone>410-550-6763</phone>
      <email>Tagboka1@jhmi.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Sean Leng, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 11, 2014</study_first_submitted>
  <study_first_submitted_qc>July 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 25, 2014</study_first_posted>
  <last_update_submitted>April 19, 2023</last_update_submitted>
  <last_update_submitted_qc>April 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Influenza, Human</mesh_term>
  </condition_browse>
  <!-- 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/NCT02200276
org study id: NA_00092365
nct id: NCT02200276
lead sponsor: 
has dmc: No
The immune system is the part of the body that protects against infection. The immune system
      often doesn't work as effectively as people get older. This research is being done to find
      out how the immune systems in older people who are over age 75 respond to influenza vaccine
      (flu shot). We also want to find out if chronic cytomegalovirus (CMV) infection, a common
      virus infection in older persons affects the immune response in people older than 75 years of
      age who receive a flu shot. The Flu Shot is a vaccine approved for the prevention of
      influenza ("Flu") infections and is recommended every year for all persons 50 years and
      older. People who are older than 75 years of age are considered healthy or frail may join. A
      total of 1025 persons will be participating in this study.

      In order to determine if you are qualified for the study, we would ask you to answer a few
      questions over the phone that will take approximately 5 minutes. If you qualify and agree to
      proceed, you will be asked to come to Johns Hopkins Bayview Medical Center or, if you are
      unable to come to Bayview, one of our staff can visit you at your home. During that visit we
      obtain consent, review your medical history, and measure your vital signs, walking speed and
      grip strength. We will also administer a few brief questionnaires and collect urine and blood
      samples. We will then give you the Influenza vaccine for free. 7 days post receiving your
      Influenza Vaccine we will collect a small blood sample for further immune system testing.
      also, you will be asked to complete a 12-question survey which will assess your symptoms over
      the past 7 days (post receiving the Influenza vaccine). Also 4 weeks post receiving your
      Influenza vaccine you will be asked to complete a third visit that will include follow up
      health questionnaires and an influenza symptoms assessment questionnaire and vital signs. A
      third blood draw will be collected (approximately 10 teaspoons) to measure immune responses
      to the influenza vaccine. In addition, you will receive your test result (CBC/w/Diff.) from
      visit #1. Throughout the influenza study season, we will call you once a week to ask about
      your general health and any Flu-like symptoms. These calls will be made throughout the Flu
      season which typically lasts through May. If you begin to have any influenza like symptoms at
      any time during the study, we ask that you call our office to report these symptoms so that
      we may perform vital signs, nasal swab to confirm influenza, and a fourth blood draw to look
      at the immune response and protection of influenza vaccine.
Seasonal influenza causes significant morbidity and mortality and is the fourth leading cause
      of death for older Americans. Annual immunization with a trivalent inactivated influenza
      vaccine (TIV) is recommended for all adults 50 years and older. However, despite improved
      vaccination coverage in older adults over time, influenza-related mortality has actually
      increased. While many TIV studies indicate its benefit for older adults as a whole, these
      studies lacked representation of the older and frail subset of the elderly who suffer over
      three-quarters of influenza-related mortality. Our pilot study funded by a Beeson K23 award
      showed significant vaccine failures in both antibody response to TIV and clinical protection
      in the frail elderly. Our preliminary data also suggest that chronic cytomegalovirus (CMV)
      infection as defined by the presence of CMV viral DNA in peripheral monocytes using a highly
      sensitive and specific nested PCR-based assay developed in our laboratory, rather than
      anti-CMV IgG serology, is associated with poor antibody and T-cell responses to TIV
      immunization as well as poor clinical protection. This is likely because anti-CMV IgG
      serology, the conventional diagnostic measure for chronic CMV infection, is a crude measure
      that merely indicates prior exposure to CMV and does not distinguish chronic (persistent)
      from past (resolved) infections. Mechanistically, precipitous immune functional decline has
      been observed in those over 75 and chronic CMV infection may contribute significantly to
      age-related immune senescent remodeling, termed immunosenescence. In order to improve our
      assessment of the effectiveness of TIV immunization and understanding of risk factors and
      underlying immune mechanisms that determine vaccine failure in adults over age 75, the frail,
      oldest old adult subset, this study is designed to conduct prospective, 4-year TIV
      immunization and post-vaccination influenza surveillance in adults over 75 years. We will
      first assess chronic CMV infection defined by detectable CMV DNA in peripheral blood
      monocytes and frailty status of the study participants and administer the Fluzone High-Dose
      TIV vaccine. Influenza-like illness (ILI) cases will be identified through post-vaccination
      influenza surveillance as previously done in the Beeson project and respiratory specimens
      obtained from ILI cases will be tested using the cutting edge PCR-based IBIS assay which can
      accurately subtype influenza and other respiratory viruses in the laboratory of Dr. Charlotte
      Gaydos in Division of Infectious Disease, a co-investigator of this project. Strain-specific
      antibody responses to TIV immunization will be measured by the standard hemogglutination
      inhibition (HI) assay. We will also evaluate T-cell responses to influenza viruses at
      baseline and after TIV immunization. Taken together, these studies will provide more accurate
      assessment of the clinical effectiveness of TIV immunization in real world geriatric
      population over age 75 and its underlying humoral and cell-mediated immune mechanisms.
      Moreover, we investigate the role of chronic CMV infection as defined by the presence of CMV
      viral DNA in peripheral monocytes as a risk factor for vaccine failure in the elderly over
      age 75. Because this oldest old subset is growing most rapidly in numbers and is at greatest
      risk for influenza-related morbidity and mortality. The long-term goal of this research is to
      strengthen immune protection against influenza for vulnerable older Americans through more
      effective and targeted immunization strategies as well as possibly through prevention and
      mitigation of chronic CMV infection.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Presence of CMV Viral DNA in Peripheral Blood Monocytes
time frame: At the end of each flu season for the next 4 years
description: To assess the role of chronic CMV infection as defined by presence of CMV viral DNA in peripheral monocytes as a risk factor for vaccine failure in this oldest old subset.
measure: Immune Responses to High Dose TIV Immunization
time frame: At the end of the study-5th year
measure: Effectiveness of High Dose TIV Immunization
time frame: At the end of the study, 5th year
description: To assess clinical effectiveness of High Dose TIV immunization in real world geriatric population over age 75 through post-vaccination influenza detection
measure: Influence of Frailty and Chronic CMV Infection on Vaccine-Induced Influenza Strain-Specific Antibody Titers and T-Cell Responses
time frame: At the end of the study, 5th year
description: To assess potential interaction between chronic CMV infection as defined above and frailty in their impact on antibody and T-cell responses to as well as clinical protection of High Dose TIV immunization in the study population.
arm group label: Influenza Immunization
arm group type: Other
description: Influenza immunization in adults over age 75
intervention type: Biological
intervention name: Influenza
arm group label: Influenza Immunization
criteria: 
gender: All
minimum age: 75 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Sean Leng
role: Principal Investigator
affiliation: Johns Hopkins University
last name: Engle Abrams
phone: 410-550-2061
email: eabrams3@jhmi.edu
last name: Janna Shapiro
phone: 410-550-2061
email: jshapi30@jh.edu
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Influenza, Human