<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/NCT01710111</url>
  </required_header>
  <id_info>
    <org_study_id>12074</org_study_id>
    <nct_id>NCT01710111</nct_id>
  </id_info>
  <brief_title>Evaluating Modes of Influenza Transmission</brief_title>
  <acronym>EMIT</acronym>
  <official_title>Evaluating Modes of Influenza Transmission Using a Human Challenge Model</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Nottingham</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Retroscreen Virology Ltd.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Wake Forest University Health Sciences</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Leeds</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Building Services Research and Information Association (BSRIA)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University College, London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Mount Sinai Hospital, New York</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Imperial College London</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Glasgow</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sydney Children's Hospitals Network</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Nottingham</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The ways in which influenza is transmitted between people are uncertain; for example, we do&#xD;
      not know if large droplets or fine particles (aerosols) matter most; both are produced by&#xD;
      coughing and sneezing. This means we cannot say what precautions work best in real life.&#xD;
      Improving our understanding is vital to allow the development of guidelines and policies to&#xD;
      help reduce the transmission of both pandemic and seasonal flu.&#xD;
&#xD;
      The aim of this study is to explore how influenza is spread, specifically by looking at the&#xD;
      importance of spread via small particles (aerosols/droplet nuclei) that are carried in&#xD;
      respiratory sprays e.g. produced by coughing and sneezing.&#xD;
&#xD;
      The primary objective of this study is:&#xD;
&#xD;
      To estimate the contribution of aerosols/droplet nuclei to influenza transmission by&#xD;
      determining the secondary attack rate (SAR) of influenza in Recipients randomised to a&#xD;
      control arm (no intervention - allowing all modes of transmission) compared to Recipients&#xD;
      randomised to an intervention arm (face shield and hand hygiene - allowing only transmission&#xD;
      by aerosols/droplet nuclei) when both groups of Recipients are exposed to Donor volunteers&#xD;
      infected with influenza via intranasal drops.&#xD;
&#xD;
      The hypothesis is that:&#xD;
&#xD;
      The SAR will be lower in Recipients exposed only to aerosols/droplet nuclei (intervention&#xD;
      arm) compared to those exposed to all modes of transmission (the control arm):&#xD;
      aerosols/droplet nuclei, droplet spray (larger respiratory droplets) and transmission through&#xD;
      contact.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The study will take place in a quarantine facility. Some volunteers (Donors) will be infected&#xD;
      with the influenza virus via droplets into the nose. Other volunteers (Recipients) will then&#xD;
      be exposed to them by occupying the same room (in the day time) and taking part in certain&#xD;
      activities e.g. playing card games. Some of the Recipients will wear face shields and clean&#xD;
      their hands regularly during the times they are with the Donors. The wearing of face shields&#xD;
      together with good hand hygiene should reduce the spread of infection through large&#xD;
      respiratory droplets and contact with contaminated surfaces but will not prevent infection&#xD;
      that occurs through aerosols in the air. Use of symptom diaries and diagnostic tests for&#xD;
      influenza will allow the presence of subsequent illness to be identified. Volunteers will be&#xD;
      required to participate in the quarantine facility for up to approximately 13 days (typically&#xD;
      9 for Donors and 13 days for Recipients), plus study screening clinics and followup.&#xD;
&#xD;
      Additionally, during the study, environmental sampling will be performed looking for the&#xD;
      presence of influenza virus. Air sampling and swabbing of surfaces and objects may provide&#xD;
      information enabling us to better understand the routes of transmission.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2013</start_date>
  <completion_date type="Actual">July 2013</completion_date>
  <primary_completion_date type="Actual">July 2013</primary_completion_date>
  <phase>N/A</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in Secondary Attack Rate (SAR)</measure>
    <time_frame>Day -2 to day 28(±3)</time_frame>
    <description>The primary endpoint is the difference in SAR of influenza in Recipients randomised to an intervention arm (face shield and hand hygiene -droplet nuclei transmission only) compared to Recipients randomised to a control arm (no intervention - all modes of transmission).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Viral parameters of infection and association with infection transmission.</measure>
    <time_frame>Day 1 to day 10</time_frame>
    <description>To evaluate and compare the incidence, duration and quantity of human virus shedding.&#xD;
To explore and compare the association of the incidence (infection rate as well as daily incidence), duration and quantity of virus shedding in Donors, with transmission to Recipients.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical parameters of infection and association with infection transmission.</measure>
    <time_frame>Day 1 to day 10</time_frame>
    <description>To explore the association and severity of self-reported influenza symptoms and pyrexia between Recipient groups (intervention vs. no intervention), both cumulatively and by individual symptom type.&#xD;
To explore the association of self-reported influenza symptoms in Donors, with transmission to Recipients, both cumulatively and by individual symptom type.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Environmental disposition of virus during infection.</measure>
    <time_frame>Day 1 to day 10</time_frame>
    <description>To determine the environmental dispersion and deposition of the virus (fomites and air) in Exposure rooms and the relationship between (a) virological findings and environmental deposition, (b) symptom scores and environmental deposition, and (c) environmental deposition and SAR in Recipients.&#xD;
To characterize the exhaled breath particle sizes and aerosolized virus copy numbers expelled by influenza inoculated and influenza exposed volunteers.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety of experimental infection in both challenged and exposed volunteers.</measure>
    <time_frame>Day 1 to day 28(±3)</time_frame>
    <description>Incidence, severity, and relationship of adverse events to challenge virus and/or study procedures.&#xD;
Changes in safety laboratory tests, vital signs and clinical tests (electrocardiogram [ECG], spirometry) from baseline</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">127</enrollment>
  <condition>Influenza, Human</condition>
  <arm_group>
    <arm_group_label>Intervention Recipients Face Shield</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Face shield and repeat hand hygiene measures</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Recipients</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>No face shield and no repeat hand hygiene measures</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Intervention Recipients Face Shield</intervention_name>
    <description>Face shield and repeat hand hygiene measures</description>
    <arm_group_label>Intervention Recipients Face Shield</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Body Weight: A total body weight ≥50 kg and a Body mass index (BMI) &gt;18 (if BMI is&#xD;
             &gt;32, a body fat percentage within WHO and NIH range for gender and age. BMI [kg/m2] =&#xD;
             Body weight [kg] ÷ Height2 [m2]&#xD;
&#xD;
          -  Contraception: Nonsterilised males must agree to refrain from fathering a child from&#xD;
             the point of entering quarantine until the Day 28 follow up visit. Use of one&#xD;
             effective form of contraception is acceptable. Sexually active females of childbearing&#xD;
             potential must agree to use 2 effective methods of avoiding pregnancy that are deemed&#xD;
             to be effective from the point of entry into the quarantine unit until the Day 28&#xD;
             follow up visit. Acceptable forms of effective contraception include:&#xD;
&#xD;
               1. Established use of oral, injected or implanted hormonal methods of contraception.&#xD;
&#xD;
               2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).&#xD;
&#xD;
               3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or&#xD;
                  cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.&#xD;
&#xD;
               4. Male sterilisation (with the appropriate postvasectomy documentation of the&#xD;
                  absence of sperm in the ejaculate). [For female subjects on the study, the&#xD;
                  vasectomised male partner should be the sole partner for that subject].&#xD;
&#xD;
               5. True abstinence: When this is in line with the preferred and usual lifestyle of&#xD;
                  the subject. [Periodic abstinence (e.g., calendar, ovulation, symptothermal,&#xD;
                  postovulation methods) and withdrawal are not acceptable methods of&#xD;
                  contraception].&#xD;
&#xD;
          -  Informed Consent: An informed consent document signed and dated by the subject and&#xD;
             investigator&#xD;
&#xD;
          -  Serosuitability: Serosuitable for challenge virus&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Smoking: Significant history of any tobacco use at any time (≥ total 10 pack year&#xD;
             history, eg. one pack a day for 10 yrs)&#xD;
&#xD;
          -  Pregnancy/Lactation: Subjects who are pregnant or nursing, or who have a positive&#xD;
             pregnancy test at any point in study&#xD;
&#xD;
          -  Previous Medical History: Presence of significant acute or chronic, uncontrolled&#xD;
             medical illness, that in the view of Investigator(s)is associated with increased risk&#xD;
             of complications of respiratory viral illness&#xD;
&#xD;
          -  Pulmonary Function: Abnormal pulmonary function in the opinion of the investigator&#xD;
             evidenced by clinically significant abnormalities in spirometry&#xD;
&#xD;
          -  Immune: History or evidence of autoimmune disease or known impaired immune&#xD;
             responsiveness (of any cause)&#xD;
&#xD;
          -  Asthma: History of asthma, COPD, pulmonary hypertension, reactive airway disease, or&#xD;
             any chronic lung condition of any aetiology.History of childhood asthma until and&#xD;
             including the age of 12 is acceptable.&#xD;
&#xD;
          -  HIV &amp; Hepatitis: Positive HIV, hepatitis B (HBV), or hepatitis C (HCV) antibody&#xD;
             screen.&#xD;
&#xD;
          -  Anatomic abnormalites of nasopharynx:Significant abnormality altering anatomy of nose&#xD;
             or nasopharynx&#xD;
&#xD;
          -  Epistaxis: Clinically significant history of epistaxis&#xD;
&#xD;
          -  Nasal Surgery: Any nasal or sinus surgery within 6 months of inoculation&#xD;
&#xD;
          -  Fainting: Recent (within the last 3 years of the screening visit) and/or recurrent&#xD;
             history of clinically significant autonomic dysfunction (e.g. recurrent episodes of&#xD;
             fainting, palpitations, etc)&#xD;
&#xD;
          -  Lab Test/ECG: Laboratory test or ECG which is abnormal and deemed by investigator(s)&#xD;
             to be clinically significant.&#xD;
&#xD;
          -  Drugs of abuse etc: Confirmed Positive test for class A drugs or alcohol that cannot&#xD;
             be satisfactorily explained&#xD;
&#xD;
          -  Venous Access: Venous access deemed inadequate for phlebotomy (and IV infusion)&#xD;
             demands of study&#xD;
&#xD;
          -  Hayfever: Subjects symptomatic with hayfever on admission or prior to inoculation.&#xD;
&#xD;
          -  Allergies: Any known allergies to excipients in challenge virus inoculum&#xD;
&#xD;
          -  Healthcare workers: Health care workers (including doctors, nurses, medical students&#xD;
             and allied healthcare professionals) anticipated to have patient contact within two&#xD;
             weeks of viral challenge. Healthcare workers should not work with patients until 14&#xD;
             days after challenge or until symptoms are fully resolved (whichever is longer). In&#xD;
             particular, health care workers who work in units housing, elderly, disabled or&#xD;
             severely immunocompromised patients (e.g. bone marrow transplant units) will be&#xD;
             excluded.&#xD;
&#xD;
          -  Household members: Presence of household member or close contact (for an additional 2&#xD;
             weeks after discharge from the isolation facility) who is:&#xD;
&#xD;
               1. less than 3 years of age&#xD;
&#xD;
               2. any person with any known immunodeficiency&#xD;
&#xD;
               3. any person receiving immunosuppressant medications&#xD;
&#xD;
               4. any person undergoing or soon to undergo cancer chemotherapy within 28 days of&#xD;
                  viral inoculation&#xD;
&#xD;
               5. any person with diagnosed emphysema or chronic obstructive pulmonary disease&#xD;
                  (COPD), is elderly residing in a nursing home, or with severe lung disease or&#xD;
                  medical condition that may include but not exclusive to conditions listed&#xD;
                  (detailed in protocol); or&#xD;
&#xD;
               6. any person who has received a transplant (bone marrow or solid organ)&#xD;
&#xD;
          -  Travel: Intending to travel within next 3 months (to countries for which travel&#xD;
             vaccinations are recommended).&#xD;
&#xD;
          -  Employers: Those employed or immediate relatives of those employed at RVL or staff/&#xD;
             students working directly for any unit in which CI works.&#xD;
&#xD;
          -  Blood loss/receipt: Receipt of blood or blood products, or loss (including blood&#xD;
             donations) of 450 mL or more of blood, during the 3 months prior to inoculations.&#xD;
&#xD;
          -  Use of nasal congestion products - acute/chronic: Acute use i.e. within 7 days prior&#xD;
             to viral challenge of any medication or other product (prescription or OTC), for&#xD;
             symptoms of hayfever, rhinitis, nasal congestion or respiratory tract infection.&#xD;
&#xD;
          -  Other IMP or virus challenges: Receipt of any investigational drug within 3 months&#xD;
             prior inoculation. Receipt of more than 4 investigational drugs within the previous 12&#xD;
             months. Prior participation in a clinical trial with same strain of respiratory virus.&#xD;
             Participation in other respiratory virus challenge within 1 year prior to challenge&#xD;
&#xD;
          -  Chemotherapy: Receipt of systemic glucocorticoids, antiviral drugs, and&#xD;
             immunoglobulin's (Igs) or other cytotoxic or immunosuppressive drug within 6 months&#xD;
             prior to dosing. Receipt of any systemic chemotherapy agent at any time.&#xD;
&#xD;
          -  Current or recent respiratory infection: Presence of significant respiratory symptoms&#xD;
             on day of challenge or between admission for challenge and challenge with/exposure to&#xD;
             virus. History suggestive of respiratory infection within 14 days prior to admission&#xD;
             for challenge exposure.&#xD;
&#xD;
          -  General screening: Any other finding in medical interview, physical exam, or screening&#xD;
             investigations that, in the opinion of the investigator, GP or sponsor, deem subject&#xD;
             unsuitable for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jonathan S Nguyen-Van-Tam, BM, BS, DM</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Nottingham</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Retroscreen Virology Ltd</name>
      <address>
        <city>London</city>
        <zip>E1 2AX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2014</verification_date>
  <study_first_submitted>October 9, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <last_update_submitted>January 14, 2014</last_update_submitted>
  <last_update_submitted_qc>January 14, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 15, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Human challenge model</keyword>
  <keyword>Quarantine study</keyword>
  <keyword>Influenza virus</keyword>
  <keyword>Modes of transmission</keyword>
  <keyword>Droplet spray</keyword>
  <keyword>Droplet nuclei</keyword>
  <keyword>Secondary attack rate</keyword>
  <keyword>Face shield</keyword>
  <keyword>Hand hygiene</keyword>
  <keyword>Fomites</keyword>
  <keyword>Environmental deposition</keyword>
  <keyword>Environmental dispersion</keyword>
  <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/NCT01710111
org study id: 12074
nct id: NCT01710111
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The ways in which influenza is transmitted between people are uncertain; for example, we do
      not know if large droplets or fine particles (aerosols) matter most; both are produced by
      coughing and sneezing. This means we cannot say what precautions work best in real life.
      Improving our understanding is vital to allow the development of guidelines and policies to
      help reduce the transmission of both pandemic and seasonal flu.

      The aim of this study is to explore how influenza is spread, specifically by looking at the
      importance of spread via small particles (aerosols/droplet nuclei) that are carried in
      respiratory sprays e.g. produced by coughing and sneezing.

      The primary objective of this study is:

      To estimate the contribution of aerosols/droplet nuclei to influenza transmission by
      determining the secondary attack rate (SAR) of influenza in Recipients randomised to a
      control arm (no intervention - allowing all modes of transmission) compared to Recipients
      randomised to an intervention arm (face shield and hand hygiene - allowing only transmission
      by aerosols/droplet nuclei) when both groups of Recipients are exposed to Donor volunteers
      infected with influenza via intranasal drops.

      The hypothesis is that:

      The SAR will be lower in Recipients exposed only to aerosols/droplet nuclei (intervention
      arm) compared to those exposed to all modes of transmission (the control arm):
      aerosols/droplet nuclei, droplet spray (larger respiratory droplets) and transmission through
      contact.
The study will take place in a quarantine facility. Some volunteers (Donors) will be infected
      with the influenza virus via droplets into the nose. Other volunteers (Recipients) will then
      be exposed to them by occupying the same room (in the day time) and taking part in certain
      activities e.g. playing card games. Some of the Recipients will wear face shields and clean
      their hands regularly during the times they are with the Donors. The wearing of face shields
      together with good hand hygiene should reduce the spread of infection through large
      respiratory droplets and contact with contaminated surfaces but will not prevent infection
      that occurs through aerosols in the air. Use of symptom diaries and diagnostic tests for
      influenza will allow the presence of subsequent illness to be identified. Volunteers will be
      required to participate in the quarantine facility for up to approximately 13 days (typically
      9 for Donors and 13 days for Recipients), plus study screening clinics and followup.

      Additionally, during the study, environmental sampling will be performed looking for the
      presence of influenza virus. Air sampling and swabbing of surfaces and objects may provide
      information enabling us to better understand the routes of transmission.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Difference in Secondary Attack Rate (SAR)
time frame: Day -2 to day 28(±3)
description: The primary endpoint is the difference in SAR of influenza in Recipients randomised to an intervention arm (face shield and hand hygiene -droplet nuclei transmission only) compared to Recipients randomised to a control arm (no intervention - all modes of transmission).
measure: Viral parameters of infection and association with infection transmission.
time frame: Day 1 to day 10
description: To evaluate and compare the incidence, duration and quantity of human virus shedding.
To explore and compare the association of the incidence (infection rate as well as daily incidence), duration and quantity of virus shedding in Donors, with transmission to Recipients.
measure: Clinical parameters of infection and association with infection transmission.
time frame: Day 1 to day 10
description: To explore the association and severity of self-reported influenza symptoms and pyrexia between Recipient groups (intervention vs. no intervention), both cumulatively and by individual symptom type.
To explore the association of self-reported influenza symptoms in Donors, with transmission to Recipients, both cumulatively and by individual symptom type.
measure: Environmental disposition of virus during infection.
time frame: Day 1 to day 10
description: To determine the environmental dispersion and deposition of the virus (fomites and air) in Exposure rooms and the relationship between (a) virological findings and environmental deposition, (b) symptom scores and environmental deposition, and (c) environmental deposition and SAR in Recipients.
To characterize the exhaled breath particle sizes and aerosolized virus copy numbers expelled by influenza inoculated and influenza exposed volunteers.
measure: Safety of experimental infection in both challenged and exposed volunteers.
time frame: Day 1 to day 28(±3)
description: Incidence, severity, and relationship of adverse events to challenge virus and/or study procedures.
Changes in safety laboratory tests, vital signs and clinical tests (electrocardiogram [ECG], spirometry) from baseline
arm group label: Intervention Recipients Face Shield
arm group type: Experimental
description: Face shield and repeat hand hygiene measures
arm group label: Control Recipients
arm group type: No Intervention
description: No face shield and no repeat hand hygiene measures
intervention type: Device
intervention name: Intervention Recipients Face Shield
description: Face shield and repeat hand hygiene measures
arm group label: Intervention Recipients Face Shield
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jonathan S Nguyen-Van-Tam, BM, BS, DM
role: Principal Investigator
affiliation: University of Nottingham
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Influenza, Human