<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/NCT03266237</url>
  </required_header>
  <id_info>
    <org_study_id>2012/01214</org_study_id>
    <nct_id>NCT03266237</nct_id>
  </id_info>
  <brief_title>The Immune Response to Influenza Vaccinations in Elderly Individuals</brief_title>
  <official_title>Multi-parameter Immune Profile Associated With the Humoral Response to Influenza Vaccine, Vaxigrip® in Healthy and Frail Elderly Subjects Aged 65-90 Years in Singapore</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National University of Singapore</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Agency for Science, Technology and Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sanofi Pasteur, a Sanofi Company</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National University Hospital, Singapore</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to characterize the immune profile of frail and healthy aged&#xD;
      individuals and investigate their immune responsiveness including the response to influenza&#xD;
      vaccine over an 18-month period. The project will include a longitudinal study to define&#xD;
      immune signatures and multi-parameter profiles associated with frailty and may lead to the&#xD;
      identification of predictive markers of evolution to frailty and Immunosenescence in the&#xD;
      elderly.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      With better healthcare available and improved accessibility, people are living longer.&#xD;
      However, a majority of older persons cannot be considered to be aging well. Approximately 70%&#xD;
      of those aged 85 years or older require frequent long hospitalizations because of their&#xD;
      increased susceptibility to infections, cancers, dementia, and other age-related health&#xD;
      problems, along with overall loss of function and autonomy associated with old age. Previous&#xD;
      studies have shown that vaccination against influenza, which significantly reduces all-cause&#xD;
      mortality in the elderly (65 years and older), was less immunogenic and effective with age.&#xD;
      Frailty, a geriatric syndrome associated with low functional activity, weight loss,&#xD;
      exhaustion, disability, decreased resilience to stressors, has been shown to increase risk&#xD;
      for adverse outcomes and death. Better understanding the relationship between aging and&#xD;
      waning immune responsiveness will enable the development of strategies to improve response to&#xD;
      vaccination in the elderly and reduce morbidity and eventually mortality associated with age&#xD;
      related complications and outcomes such as infectious diseases or frailty. A comprehensive&#xD;
      analysis of the immune phenotype and function after antigenic challenge in older individuals&#xD;
      would be a unique approach to understand (i) the potential associations between aging,&#xD;
      impaired immune function and transition to frailty, (ii) which components of the immune&#xD;
      system are altered with aging (innate vs adaptive immunity) and (iii) if early and/or late&#xD;
      immune responses are preferentially altered with aging and frailty.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>December 2013</start_date>
  <completion_date type="Actual">May 2016</completion_date>
  <primary_completion_date type="Actual">May 2016</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The Immune Responsiveness of Elderly Subjects when Administered Influenza Vaccination as Measured by HAI</measure>
    <time_frame>18-month period</time_frame>
    <description>Hemagglutination Inhibition (HAI) titer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cellular Immune Response and Inflammatory Profile of elderly subjects when administered influenza vaccination - Flu-Specific T cells</measure>
    <time_frame>18 months</time_frame>
    <description>% Flu-specific T cells out of total PBMCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Flu-Specific B Cell Response</measure>
    <time_frame>18 months</time_frame>
    <description>No. of flu-specific B cells quantified out of 1x105 PBMCs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inflammatory Markers</measure>
    <time_frame>18 months</time_frame>
    <description>Quantitative (pg/mL analyte, picogram of analyte per milliliter of plasma)</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Clinical Assessments of the elderly subjects - Weight</measure>
    <time_frame>18 months</time_frame>
    <description>Quantitative Weight (kg, kilograms)</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical Assessments of the elderly subjects - Height</measure>
    <time_frame>18 months</time_frame>
    <description>Quantitative Height (m, meters)</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical Assessments of the elderly subjects - BMI</measure>
    <time_frame>18 months</time_frame>
    <description>Quantitative BMI (weight and height will be combined to report in kg/m2)</description>
  </other_outcome>
  <other_outcome>
    <measure>Clinical Assessments of the elderly subjects - DXA</measure>
    <time_frame>18 months</time_frame>
    <description>Quantitative Dual-Energy X-Ray Absorptiometry (DXA) scan: Standardized Muscle Index (appendicular lean mass / height-squared); T-score based on Bone Mineral Density BMD (appendicular lean mass and height will be combined to report in g/cm2)</description>
  </other_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">240</enrollment>
  <condition>Influenza</condition>
  <arm_group>
    <arm_group_label>Healthy Adult</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy adult participants aged 21-40 years will be vaccinated with Vaxigrip® influenza vaccine</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Elderly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Elderly Pre-Frail</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Elderly Frail</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vaxigrip®</intervention_name>
    <description>To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.</description>
    <arm_group_label>Healthy Adult</arm_group_label>
    <arm_group_label>Healthy Elderly</arm_group_label>
    <arm_group_label>Healthy Elderly Frail</arm_group_label>
    <arm_group_label>Healthy Elderly Pre-Frail</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Aged ≥ 65 years and &lt;90 years on the day of inclusion for the elderly group, and ≥&#xD;
             21-&lt;40 for the adult group.&#xD;
&#xD;
          2. Informed consent form has been signed and dated.&#xD;
&#xD;
          3. Able to attend all scheduled visits and to comply with all trial procedures.&#xD;
&#xD;
          4. Living at home.&#xD;
&#xD;
          5. Able to walk without personal assistance and no other physical limitations that can&#xD;
             limit participation.&#xD;
&#xD;
          6. Recruited from the cohort in Singapore Longitudinal Ageing Study-II (SLAS-II), as well&#xD;
             as from sites in West Jurong and from Outpatient clinics at National University&#xD;
             Hospital (NUH).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participation at the time of study enrollment (or in the 4 weeks preceding trial&#xD;
             vaccination) or planned participation during the present trial period in another&#xD;
             clinical trial investigating vaccine, drug, medical device, or medical procedure.&#xD;
&#xD;
          2. Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned&#xD;
             receipt of any vaccine in the 4 weeks following trial vaccination, including influenza&#xD;
             vaccination. However, 23-valent pneumococcal vaccine and tetanus vaccine will be&#xD;
             allowed during this time window.&#xD;
&#xD;
          3. Receipt of an influenza vaccine within the 6 months preceding the trial vaccination or&#xD;
             planned influenza vaccination during the trial.&#xD;
&#xD;
          4. Known or suspected congenital or acquired immunodeficiency or receipt of&#xD;
             immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy,&#xD;
             within the preceding 6 months; or long-term systemic corticosteroid therapy&#xD;
             (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).&#xD;
&#xD;
          5. Systemic hypersensitivity to eggs, chicken proteins, or any of the vaccine components&#xD;
             or a history of a life-threatening reaction to Vaxigrip® or to a vaccine containing&#xD;
             any of the same substances.&#xD;
&#xD;
          6. Deprived of freedom by an administrative or court order, or in an emergency setting,&#xD;
             or hospitalized involuntarily.&#xD;
&#xD;
          7. Current alcohol or drug addiction.&#xD;
&#xD;
          8. Chronic illness that, in the opinion of the investigator, is at a stage where it might&#xD;
             interfere with trial conduct or completion.&#xD;
&#xD;
          9. Identified as an Investigator or employee of the Investigator or study centre with&#xD;
             direct involvement in the proposed study, or identified as an immediate family member&#xD;
             (i.e. parent, spouse) of the Investigator or employee with direct involvement in the&#xD;
             proposed study.&#xD;
&#xD;
         10. Severe audio-visual impairment.&#xD;
&#xD;
         11. Dementia, severe cognitive impairment (MMSE &lt;18), major depression or other psychotic&#xD;
             disorders.&#xD;
&#xD;
         12. Progressive, degenerative neurologic disease: e.g. Alzheimer's disease.&#xD;
&#xD;
         13. Rapidly progressive or terminal illness under palliative care with life expectancy&#xD;
             less than 12 months.&#xD;
&#xD;
         14. Primary severely muscle/joint disorders resulting in physical disability interfering&#xD;
             with the physical performance tests needed for the study.&#xD;
&#xD;
         15. Hospital admission in the past 6 weeks.&#xD;
&#xD;
         16. (Relevant for the healthy young adults subjects group). Subject is pregnant (or&#xD;
             positive urine pregnancy test), or lactating, or of childbearing potential (to be&#xD;
             considered of non-childbearing potential, a female must be postmenopausal for at least&#xD;
             1 year, surgically sterile, or using an effective method of contraception or&#xD;
             abstinence from at least 4 weeks prior to vaccination and until at least 4 weeks after&#xD;
             vaccination).&#xD;
&#xD;
         17. Self-reported thrombocytopenia, contraindicating intramuscular vaccination&#xD;
&#xD;
         18. Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding vaccination,&#xD;
             contraindicating intramuscular vaccination upon investigator's judgement.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Professor Paul Anantharajah Tambyah, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University of Singapore</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Moral Neighbourhood Link @ Telok Blangah</name>
      <address>
        <city>Singapore</city>
        <zip>090003</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119228</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>THK Seniors Activity Centre @ Henderson (Satellite 93)</name>
      <address>
        <city>Singapore</city>
        <zip>150093</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Moral Neighbourhood Link (Bukit Merah View)</name>
      <address>
        <city>Singapore</city>
        <zip>150118</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>THK Seniors Activity Centre @ Beo Crescent</name>
      <address>
        <city>Singapore</city>
        <zip>160044</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SARAH Senior Activity Centre</name>
      <address>
        <city>Singapore</city>
        <zip>160105</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>THK Seniors Service @ Taman Jurong</name>
      <address>
        <city>Singapore</city>
        <zip>610337</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>TaRa @ Jurong Point, Jurong West Central 2</name>
      <address>
        <city>Singapore</city>
        <zip>648886</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Outpatient Clinic, St Luke's Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>659674</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>September 20, 2016</study_first_submitted>
  <study_first_submitted_qc>August 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 30, 2017</study_first_posted>
  <last_update_submitted>August 27, 2017</last_update_submitted>
  <last_update_submitted_qc>August 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 30, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Influenza</keyword>
  <keyword>Influenza Virus Vaccines</keyword>
  <keyword>Vaxigrip</keyword>
  <keyword>Respiratory Tract Infections</keyword>
  <keyword>Orthomyxoviridae Infections</keyword>
  <keyword>Frailty</keyword>
  <keyword>Aging</keyword>
  <keyword>Safety</keyword>
  <keyword>Immunogenicity</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>Yes</sharing_ipd>
    <ipd_description>Publication of the data in peer-reviewed journals</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>five years approx</ipd_time_frame>
    <ipd_access_criteria>through a research agreement</ipd_access_criteria>
  </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/NCT03266237
org study id: 2012/01214
nct id: NCT03266237
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The aim of this study is to characterize the immune profile of frail and healthy aged
      individuals and investigate their immune responsiveness including the response to influenza
      vaccine over an 18-month period. The project will include a longitudinal study to define
      immune signatures and multi-parameter profiles associated with frailty and may lead to the
      identification of predictive markers of evolution to frailty and Immunosenescence in the
      elderly.
With better healthcare available and improved accessibility, people are living longer.
      However, a majority of older persons cannot be considered to be aging well. Approximately 70%
      of those aged 85 years or older require frequent long hospitalizations because of their
      increased susceptibility to infections, cancers, dementia, and other age-related health
      problems, along with overall loss of function and autonomy associated with old age. Previous
      studies have shown that vaccination against influenza, which significantly reduces all-cause
      mortality in the elderly (65 years and older), was less immunogenic and effective with age.
      Frailty, a geriatric syndrome associated with low functional activity, weight loss,
      exhaustion, disability, decreased resilience to stressors, has been shown to increase risk
      for adverse outcomes and death. Better understanding the relationship between aging and
      waning immune responsiveness will enable the development of strategies to improve response to
      vaccination in the elderly and reduce morbidity and eventually mortality associated with age
      related complications and outcomes such as infectious diseases or frailty. A comprehensive
      analysis of the immune phenotype and function after antigenic challenge in older individuals
      would be a unique approach to understand (i) the potential associations between aging,
      impaired immune function and transition to frailty, (ii) which components of the immune
      system are altered with aging (innate vs adaptive immunity) and (iii) if early and/or late
      immune responses are preferentially altered with aging and frailty.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: The Immune Responsiveness of Elderly Subjects when Administered Influenza Vaccination as Measured by HAI
time frame: 18-month period
description: Hemagglutination Inhibition (HAI) titer
measure: Cellular Immune Response and Inflammatory Profile of elderly subjects when administered influenza vaccination - Flu-Specific T cells
time frame: 18 months
description: % Flu-specific T cells out of total PBMCs
measure: Flu-Specific B Cell Response
time frame: 18 months
description: No. of flu-specific B cells quantified out of 1x105 PBMCs
measure: Inflammatory Markers
time frame: 18 months
description: Quantitative (pg/mL analyte, picogram of analyte per milliliter of plasma)
measure: Clinical Assessments of the elderly subjects - Weight
time frame: 18 months
description: Quantitative Weight (kg, kilograms)
measure: Clinical Assessments of the elderly subjects - Height
time frame: 18 months
description: Quantitative Height (m, meters)
measure: Clinical Assessments of the elderly subjects - BMI
time frame: 18 months
description: Quantitative BMI (weight and height will be combined to report in kg/m2)
measure: Clinical Assessments of the elderly subjects - DXA
time frame: 18 months
description: Quantitative Dual-Energy X-Ray Absorptiometry (DXA) scan: Standardized Muscle Index (appendicular lean mass / height-squared); T-score based on Bone Mineral Density BMD (appendicular lean mass and height will be combined to report in g/cm2)
arm group label: Healthy Adult
arm group type: Experimental
description: Healthy adult participants aged 21-40 years will be vaccinated with Vaxigrip® influenza vaccine
arm group label: Healthy Elderly
arm group type: Experimental
description: Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
arm group label: Healthy Elderly Pre-Frail
arm group type: Experimental
description: Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
arm group label: Healthy Elderly Frail
arm group type: Experimental
description: Healthy Elderly participants aged 65-90 years will be vaccinated with Vaxigrip® influenza vaccine.
intervention type: Drug
intervention name: Vaxigrip®
description: To describe the humoral immune response to Vaxigrip (IM) vaccination at Day 0 (baseline) and Day 28 according to the age and frailty status at baseline (i.e. in each study group) for each Influenza strain.
arm group label: Healthy Adult
arm group label: Healthy Elderly
arm group label: Healthy Elderly Frail
arm group label: Healthy Elderly Pre-Frail
criteria: 
gender: All
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Professor Paul Anantharajah Tambyah, MD
role: Principal Investigator
affiliation: National University of Singapore
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Singapore
responsible party type: Sponsor
mesh term: Influenza, Human
sharing ipd: Yes
ipd description: Publication of the data in peer-reviewed journals
ipd info type: Study Protocol
ipd time frame: five years approx
ipd access criteria: through a research agreement