<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/NCT04487041</url>
  </required_header>
  <id_info>
    <org_study_id>20200752</org_study_id>
    <nct_id>NCT04487041</nct_id>
  </id_info>
  <brief_title>Tfh Dysfunction in HIV and Aging</brief_title>
  <official_title>Tfh Dysfunction in HIV and Aging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Miami</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Miami</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this research is to evaluate blood samples from HIV infected and non-HIV&#xD;
      infected people to understand how aging and HIV infection affect the immune responses (body&#xD;
      defenses against infection) to the flu vaccine.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 30, 2020</start_date>
  <completion_date type="Anticipated">September 30, 2025</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2025</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>Sequential Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in HAI antibody response</measure>
    <time_frame>Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)</time_frame>
    <description>Change in mean titers of Hemagglutination inhibition (HAI) antibody response will be measured using serum sample.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in neutralization antibody response</measure>
    <time_frame>Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)</time_frame>
    <description>Change in mean titers of neutralization antibody response will be measured using serum sample.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants with Vaccine Response</measure>
    <time_frame>Month 13 (1 month post high-dose flu vaccination)</time_frame>
    <description>Percentage of participants that are vaccine responders and non-responders will be reported. Response is evaluated using seroconversion to the flu vaccine using serum sample.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of T-follicular helper (Tfh) cells</measure>
    <time_frame>Month 13 (1 month post high-dose flu vaccination)</time_frame>
    <description>Percentage of Tfh cells as measured using peripheral blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of B cells</measure>
    <time_frame>Month 13 (1 month post high-dose flu vaccination)</time_frame>
    <description>Percentage of B cells as measured using peripheral blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of monocytes</measure>
    <time_frame>Month 13 (1 month post high-dose flu vaccination)</time_frame>
    <description>Percentage of monocytes as measured using peripheral blood samples</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Tfh cells producing cytokines</measure>
    <time_frame>Month 13 (1 month post high-dose flu vaccination)</time_frame>
    <description>Percentage of Tfh cells producing cytokines as measured using peripheral blood samples</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">400</enrollment>
  <condition>Human Influenza</condition>
  <arm_group>
    <arm_group_label>Young HIV negative group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>HIV uninfected participants that are 18-35 years of age will receive the standard dose flu vaccine. Participants who did not respond to the standard dose flu vaccination, as defined by less than a four-fold increase in flu antibody titer from baseline, will then receive the high dose flu vaccination 1 year after initial standard dose flu vaccination. Participants who respond to the standard dose flu vaccination will not receive the high dose flu vaccination.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Young HIV positive group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 18-35 years of age, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Old HIV negative group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV uninfected participants that are 65 years and older will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Old HIV positive group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 65 years and older, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Standard dose influenza vaccination</intervention_name>
    <description>Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle</description>
    <arm_group_label>Old HIV negative group</arm_group_label>
    <arm_group_label>Old HIV positive group</arm_group_label>
    <arm_group_label>Young HIV negative group</arm_group_label>
    <arm_group_label>Young HIV positive group</arm_group_label>
    <other_name>Fluzone quadrivalent</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>High dose influenza vaccination</intervention_name>
    <description>4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle</description>
    <arm_group_label>Old HIV negative group</arm_group_label>
    <arm_group_label>Old HIV positive group</arm_group_label>
    <arm_group_label>Young HIV negative group</arm_group_label>
    <arm_group_label>Young HIV positive group</arm_group_label>
    <other_name>Fluzone high dose quadrivalent</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. For HIV positive participants:&#xD;
&#xD;
               -  HIV infection, as documented by any licensed ELISA test kit. Participants on ART&#xD;
                  as a result of prior HIV documented infection will not be required to provide&#xD;
                  proof of diagnosis of HIV infection.&#xD;
&#xD;
               -  Additional criteria for HIV positive&#xD;
&#xD;
                    1. on ART for at least 1 year. Occasional viral blips up to 1000 copies/ml also&#xD;
                       acceptable provided the patients are on continuing treatment,&#xD;
&#xD;
                    2. Cluster of differentiation 4 (CD4) count available in the prior 6 months and&#xD;
                       &gt;200/mm3&#xD;
&#xD;
                    3. Undetectable viral load (&lt; 40 copies/mL). Blips of &lt;1000 copies/mL will be&#xD;
                       allowed.&#xD;
&#xD;
          2. For HIV negative participants:&#xD;
&#xD;
               -  Documented negative HIV test at the time of study entry, either by any licensed&#xD;
                  ELISA.&#xD;
&#xD;
          3. For all participants:&#xD;
&#xD;
               1. Individuals age: ≤35 years and ≥65 years.&#xD;
&#xD;
               2. No history of other immunodeficiency disorders&#xD;
&#xD;
               3. Not on steroid or other immunosuppressive/immunomodulators medications.&#xD;
&#xD;
               4. No active malignancies.&#xD;
&#xD;
               5. Agreeable to receive both regular standard (STD-TIV) and high dose (HD-TIV)&#xD;
                  influenza vaccination.&#xD;
&#xD;
               6. Agreeable to participate in study for a complete course of study full visits&#xD;
                  including 2 consecutive flu seasons.&#xD;
&#xD;
               7. Able to provide informed consent.&#xD;
&#xD;
        Exclusion criteria&#xD;
&#xD;
          1. Contraindication to receive influenza vaccination.&#xD;
&#xD;
          2. Non-adherence to ART for HIV positive&#xD;
&#xD;
          3. Unable to provide informed consent.&#xD;
&#xD;
          4. Influenza vaccination already given during the current vaccination season.&#xD;
&#xD;
          5. Known drug abuse including cocaine by history&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Savita Pahwa, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Miami</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Suresh Pallikkuth, PhD</last_name>
    <phone>3052435315</phone>
    <email>spallikkuth@med.miami.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Suresh Pallikkuth, PhD</last_name>
      <phone>305-243-5315</phone>
      <email>spallikkuth@med.miami.edu</email>
    </contact>
    <investigator>
      <last_name>Savita Pahwa, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Suresh Pallikkuth, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>July 22, 2020</study_first_submitted>
  <study_first_submitted_qc>July 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 27, 2020</study_first_posted>
  <last_update_submitted>October 17, 2022</last_update_submitted>
  <last_update_submitted_qc>October 17, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 19, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Miami</investigator_affiliation>
    <investigator_full_name>Savita Pahwa</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>HIV</keyword>
  <keyword>Aging</keyword>
  <keyword>flu vaccination</keyword>
  <keyword>high dose vaccination</keyword>
  <keyword>immune function</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>
  <!-- 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/NCT04487041
org study id: 20200752
nct id: NCT04487041
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this research is to evaluate blood samples from HIV infected and non-HIV
      infected people to understand how aging and HIV infection affect the immune responses (body
      defenses against infection) to the flu vaccine.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in HAI antibody response
time frame: Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)
description: Change in mean titers of Hemagglutination inhibition (HAI) antibody response will be measured using serum sample.
measure: Change in neutralization antibody response
time frame: Baseline to Month 6 (post standard dose flu vaccination), Baseline to Month 18 (post high-dose flu vaccination)
description: Change in mean titers of neutralization antibody response will be measured using serum sample.
measure: Percentage of Participants with Vaccine Response
time frame: Month 13 (1 month post high-dose flu vaccination)
description: Percentage of participants that are vaccine responders and non-responders will be reported. Response is evaluated using seroconversion to the flu vaccine using serum sample.
measure: Percentage of T-follicular helper (Tfh) cells
time frame: Month 13 (1 month post high-dose flu vaccination)
description: Percentage of Tfh cells as measured using peripheral blood samples
measure: Percentage of B cells
time frame: Month 13 (1 month post high-dose flu vaccination)
description: Percentage of B cells as measured using peripheral blood samples
measure: Percentage of monocytes
time frame: Month 13 (1 month post high-dose flu vaccination)
description: Percentage of monocytes as measured using peripheral blood samples
measure: Percentage of Tfh cells producing cytokines
time frame: Month 13 (1 month post high-dose flu vaccination)
description: Percentage of Tfh cells producing cytokines as measured using peripheral blood samples
arm group label: Young HIV negative group
arm group type: Active Comparator
description: HIV uninfected participants that are 18-35 years of age will receive the standard dose flu vaccine. Participants who did not respond to the standard dose flu vaccination, as defined by less than a four-fold increase in flu antibody titer from baseline, will then receive the high dose flu vaccination 1 year after initial standard dose flu vaccination. Participants who respond to the standard dose flu vaccination will not receive the high dose flu vaccination.
arm group label: Young HIV positive group
arm group type: Experimental
description: HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 18-35 years of age, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.
arm group label: Old HIV negative group
arm group type: Experimental
description: HIV uninfected participants that are 65 years and older will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.
arm group label: Old HIV positive group
arm group type: Experimental
description: HIV infected viral suppressed participants, who are on anti-retroviral therapy (ART) aged 65 years and older, will receive the standard dose flu vaccine first followed by the high dose flu vaccine 1 year after initial standard dose.
intervention type: Biological
intervention name: Standard dose influenza vaccination
description: Single 0.5 ml injection administered intramuscularly into participant's deltoid muscle
arm group label: Old HIV negative group
arm group label: Old HIV positive group
arm group label: Young HIV negative group
arm group label: Young HIV positive group
other name: Fluzone quadrivalent
intervention type: Biological
intervention name: High dose influenza vaccination
description: 4 times more concentrated single 0.7 ml injection administered intramuscularly into participant's deltoid muscle
arm group label: Old HIV negative group
arm group label: Old HIV positive group
arm group label: Young HIV negative group
arm group label: Young HIV positive group
other name: Fluzone high dose quadrivalent
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Savita Pahwa, MD
role: Principal Investigator
affiliation: University of Miami
last name: Suresh Pallikkuth, PhD
phone: 3052435315
email: spallikkuth@med.miami.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Miami
investigator full name: Savita Pahwa
investigator title: Professor
mesh term: Influenza, Human
sharing ipd: No