<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/NCT04475081</url>
  </required_header>
  <id_info>
    <org_study_id>PF-1214</org_study_id>
    <nct_id>NCT04475081</nct_id>
  </id_info>
  <brief_title>Use of a Live Attenuated Vaccine as an Immune-based Preventive Against COVID-19-associated Sepsis</brief_title>
  <official_title>Use of a Live Attenuated Vaccine Repurposed as an Innate Immune-based Preventive Against COVID-19-associated Sepsis/Inflammation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Louisiana State University Health Sciences Center in New Orleans</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parsemus Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Louisiana State University Health Sciences Center in New Orleans</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 objective of this randomized clinical trial is to test whether administration of live&#xD;
      attenuated MMR vaccine (measles mumps rubella; Merck) to eligible adults at highest risk for&#xD;
      contracting COVID-19 (healthcare workers, first responders), can induce non-specific trained&#xD;
      innate immune leukocytes that can prevent/dampen pathological inflammation and sepsis&#xD;
      associated with COVID-19-infection, if exposed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Clinical Design. Eligible healthcare workers (HCW) or first responders in the greater New&#xD;
      Orleans area (n=60) meeting eligibility criteria will be enrolled into a 12 month study by&#xD;
      the Louisiana State University Health Sciences Center Clinical &amp; Translational Research&#xD;
      Center (LSUHSC CTRC) clinical staff affiliated with the Louisiana Clinical and Translational&#xD;
      Research Science (LA CaTS) Center and blindly randomized to receive the live attenuated&#xD;
      M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection in the arm at a&#xD;
      baseline visit following informed consent. Subjects will be recruited from local hospitals&#xD;
      and EMS stations throughout the greater New Orleans area by distributing recruitment flyers&#xD;
      at the local facilities. The flyers will have contact information for HCWs and EMS first&#xD;
      responders to call for more information or to schedule an appointment. Additionally, subjects&#xD;
      may be referred to the study by other HCWs or first responders aware of study activities.&#xD;
      Subject consenting, interviewing, vaccine administration and biospecimen collection will be&#xD;
      performed by the CTRC staff, under full Personal Protective Equipment (PPE) protection.&#xD;
      Following informed consent, subjects will be asked to complete the Baseline Demographic &amp;&#xD;
      History Questionnaire disclosing their demographic information, employment, medication,&#xD;
      vaccination, and medical history. Specifically, the medical history will place emphasis on&#xD;
      the presence of diabetes, hypertension, heart disease, and their treatments/medications.&#xD;
      Subjects will then have their height, weight, body mass index (BMI), vital signs, and pulse&#xD;
      oximetry measured. Subjects will also have their body composition and fat percentage measured&#xD;
      using the BOD POD Body Composition Tracking System. Female subjects of childbearing potential&#xD;
      will be given a urine-based pregnancy test. Approximately 10cc of blood will be collected&#xD;
      along with a nasopharyngeal swab for baseline laboratory analysees (serology, RNA, flow&#xD;
      cytometry). When available, a finger prick blood sample will be obtained in addition to the&#xD;
      other biospecimens for COVID-19 serological analysis. Those subjects that satisfy the&#xD;
      inclusion and exclusion criteria (Eligibility Criteria) will be blindly randomized to receive&#xD;
      the live attenuated M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection.&#xD;
      Repeat biosampling will occur on days 14, 30, 60, and at 12 months post-vaccination. At each&#xD;
      follow-up, anthropometric measurements, vital signs measurement, and symptom assessment for&#xD;
      the presence of symptoms related to COVID-19 infection (fever, headache, myalgia, cough, loss&#xD;
      of taste or smell, breathing problems), general well-being (i.e., pain, dental concerns,&#xD;
      sleep patterns, general stress level, fatigue), and any changes in medications, medical&#xD;
      status, and employment will be collected utilizing the Follow-up Symptom &amp; History&#xD;
      Questionnaire. Telephone follow-up calls utilizing the Follow-up Symptom Assessment &amp; History&#xD;
      Questionnaire will be made on a monthly basis between the 60-day follow-up visit and the&#xD;
      12-month endpoint visit. Should a subject develop symptoms potentially associated with&#xD;
      COVID-19 infection at any point during the 12-month study period, that subject will be seen&#xD;
      in the clinic by the Infectious Disease (ID) Co-investigator, and a repeat collection of&#xD;
      blood and nasopharyngeal biospecimens will be performed for analysis, and the subject will be&#xD;
      asked to complete the Follow-up Symptom &amp; History Questionnaire and get another body&#xD;
      composition analysis via BOD POD. Subjects will be asked to report the development of any&#xD;
      potential COVID-19 infection-related symptoms or positive COVID-19 infection testing outside&#xD;
      of the study, as well as any symptoms potentially related to MMR vaccination. Should a&#xD;
      subject become admitted to the hospital related to COVID-19 infection, in-patient information&#xD;
      will be obtained via the electronic medical record (EMR) when available.&#xD;
&#xD;
      Primary outcome measures will be peripheral blood monocytic MDSCs (M-MDSC) and/or&#xD;
      granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples.&#xD;
      Specifically, documented increases in the MDSCs per subject from baseline through 30-60 days&#xD;
      post-vaccination is expected in the MMR group compared to placebo group. Measles antibody are&#xD;
      also expected to increase in the MMR group and will serve as a control for the MMR&#xD;
      vaccination. Stationary levels of MDSCs and measles antibodies are expected in the MMR group&#xD;
      over the 12-month period.&#xD;
&#xD;
      The investigators will perform the COVID-19 RNA testing at baseline, 14, 30, and 60 days&#xD;
      post-vaccination, and at any point over the 12-month period that symptoms arise. All patients&#xD;
      that are COVID-19+ at baseline or become COVID-19+ through the study will be included for&#xD;
      secondary outcome analyses. The Secondary outcome measures will be COVID-19 antibodies&#xD;
      (seropositive) as evidence of infection, sepsis/lung inflammation, ICU/ventilator usage,&#xD;
      in-patient health related co-morbidities and self-reporting mental status (such as general&#xD;
      fatigue/stress level) over the 12-month period post-vaccination. In-patient information will&#xD;
      be obtained through the EMR when available. Out-patient information will be obtained via&#xD;
      self-reporting utilizing the Follow-up Symptom &amp; History Questionnaire.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 22, 2020</start_date>
  <completion_date type="Actual">May 15, 2022</completion_date>
  <primary_completion_date type="Actual">May 15, 2022</primary_completion_date>
  <phase>Phase 3</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>
    <intervention_model_description>MMR vaccine vs placebo</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Randomized by study nurse</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Induction of myeloid-derived suppressor cells (MDSCs)</measure>
    <time_frame>14 days post-vaccination</time_frame>
    <description>peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Induction of MDSCs</measure>
    <time_frame>30 days post vaccination</time_frame>
    <description>peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Induction of MDSCs</measure>
    <time_frame>60 days post vaccination</time_frame>
    <description>peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Induction of MDSCs</measure>
    <time_frame>12 months post vaccination</time_frame>
    <description>peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>COVID-19 infection positive</measure>
    <time_frame>14 days post-vaccination</time_frame>
    <description>COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COVID-19 infection positive</measure>
    <time_frame>30 days post-vaccination</time_frame>
    <description>COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COVID-19 infection positive</measure>
    <time_frame>60 days post-vaccination</time_frame>
    <description>COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>COVID-19 infection positive</measure>
    <time_frame>12 months post-vaccination</time_frame>
    <description>COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>14 days post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>30 days post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>60 days post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>3 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>4 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>5 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>6 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>7 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>8 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>9 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>10 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>11 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health questionnaire</measure>
    <time_frame>12 months post-vaccination</time_frame>
    <description>Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">35</enrollment>
  <condition>Sepsis Syndrome</condition>
  <arm_group>
    <arm_group_label>MMR vaccination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will be randomized to receive the MMR Vaccine subcutaneously</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects will be randomized to receive sterile saline given subcutaneously</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>MMR vaccine</intervention_name>
    <description>Merck MMR-II vaccine</description>
    <arm_group_label>MMR vaccination</arm_group_label>
    <arm_group_label>Placebo control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18-70 years of age&#xD;
&#xD;
          -  Employed as a HCW (hospital, outpatient clinic, private office or 1st responder (EMS)&#xD;
             in the greater New Orleans region&#xD;
&#xD;
          -  Able to provide a signed and dated informed consent&#xD;
&#xD;
          -  Able to provide pre-randomized blood specimen&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any known MMR vaccine contraindication&#xD;
&#xD;
          -  Fever&#xD;
&#xD;
          -  Weakened resistance toward infections due to a disease in/of the immune system&#xD;
&#xD;
          -  Individuals receiving medical treatment that affects the immune response or other&#xD;
             immunosuppressive therapy in the last year (see excluded medications).&#xD;
&#xD;
          -  Individuals with a congenital cellular immunodeficiency&#xD;
&#xD;
          -  Individuals with a malignancy involving bone marrow or lymphoid systems&#xD;
&#xD;
          -  Individuals with any serious underlying illness (such as malignancy). People with&#xD;
             cardiovascular disease, hypertension, diabetes, and/or chronic respiratory disease are&#xD;
             eligible if not immunocompromised (at the discretion of the ID Co-investigator)&#xD;
&#xD;
          -  Individuals with known or suspected HIV infection, even if asymptomatic or has normal&#xD;
             immune function. (Due to the risk of disseminated MMR infection)&#xD;
&#xD;
          -  Individuals with an active skin disease such as eczema, dermatitis or psoriasis at or&#xD;
             near the site of vaccination. A different site can be chosen if necessary&#xD;
&#xD;
          -  Pregnant or women who think they may test positive for pregnancy in this next month&#xD;
             following MMR vaccine administration.&#xD;
&#xD;
          -  Individuals who have received a MMR or another live vaccine (i.e., Zostavax, nasal flu&#xD;
             vaccine) within the last year&#xD;
&#xD;
          -  Individuals with known anaphylactic reaction to any of the ingredients present in the&#xD;
             MMR vaccine&#xD;
&#xD;
          -  Individuals previously testing positive for SARS-CoV-2 or documented seropositive for&#xD;
             SARS-CoV-2 antibodies prior to enrollment in this study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paul L Fidel, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Louisiana State University Health Sciences Center - New Orleans</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Clinical and Translational Research Center</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Fidel PL Jr, Noverr MC. Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection? mBio. 2020 Jun 19;11(3):e00907-20. doi: 10.1128/mBio.00907-20.</citation>
    <PMID>32561657</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Louisiana State University Health Sciences Center in New Orleans</investigator_affiliation>
    <investigator_full_name>Paul Fidel</investigator_full_name>
    <investigator_title>Professor and Associate Dean</investigator_title>
  </responsible_party>
  <keyword>MMR vaccine</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Sepsis</keyword>
  <keyword>trained innate immunity</keyword>
  <keyword>myeloid-derived suppressor cells</keyword>
  <keyword>inflammation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Sepsis</mesh_term>
    <mesh_term>Toxemia</mesh_term>
    <mesh_term>Systemic Inflammatory Response Syndrome</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We plan to share de-identified participant data to other researchers at their request and with justification. Primary and secondary outcome measures will be shared</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_time_frame>2 years</ipd_time_frame>
    <ipd_access_criteria>If fully justified for additional research purposes</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/NCT04475081
org study id: PF-1214
nct id: NCT04475081
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The objective of this randomized clinical trial is to test whether administration of live
      attenuated MMR vaccine (measles mumps rubella; Merck) to eligible adults at highest risk for
      contracting COVID-19 (healthcare workers, first responders), can induce non-specific trained
      innate immune leukocytes that can prevent/dampen pathological inflammation and sepsis
      associated with COVID-19-infection, if exposed.
Clinical Design. Eligible healthcare workers (HCW) or first responders in the greater New
      Orleans area (n=60) meeting eligibility criteria will be enrolled into a 12 month study by
      the Louisiana State University Health Sciences Center Clinical & Translational Research
      Center (LSUHSC CTRC) clinical staff affiliated with the Louisiana Clinical and Translational
      Research Science (LA CaTS) Center and blindly randomized to receive the live attenuated
      M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection in the arm at a
      baseline visit following informed consent. Subjects will be recruited from local hospitals
      and EMS stations throughout the greater New Orleans area by distributing recruitment flyers
      at the local facilities. The flyers will have contact information for HCWs and EMS first
      responders to call for more information or to schedule an appointment. Additionally, subjects
      may be referred to the study by other HCWs or first responders aware of study activities.
      Subject consenting, interviewing, vaccine administration and biospecimen collection will be
      performed by the CTRC staff, under full Personal Protective Equipment (PPE) protection.
      Following informed consent, subjects will be asked to complete the Baseline Demographic &
      History Questionnaire disclosing their demographic information, employment, medication,
      vaccination, and medical history. Specifically, the medical history will place emphasis on
      the presence of diabetes, hypertension, heart disease, and their treatments/medications.
      Subjects will then have their height, weight, body mass index (BMI), vital signs, and pulse
      oximetry measured. Subjects will also have their body composition and fat percentage measured
      using the BOD POD Body Composition Tracking System. Female subjects of childbearing potential
      will be given a urine-based pregnancy test. Approximately 10cc of blood will be collected
      along with a nasopharyngeal swab for baseline laboratory analysees (serology, RNA, flow
      cytometry). When available, a finger prick blood sample will be obtained in addition to the
      other biospecimens for COVID-19 serological analysis. Those subjects that satisfy the
      inclusion and exclusion criteria (Eligibility Criteria) will be blindly randomized to receive
      the live attenuated M-M-R® II vaccine or placebo (sterile saline) via subcutaneous injection.
      Repeat biosampling will occur on days 14, 30, 60, and at 12 months post-vaccination. At each
      follow-up, anthropometric measurements, vital signs measurement, and symptom assessment for
      the presence of symptoms related to COVID-19 infection (fever, headache, myalgia, cough, loss
      of taste or smell, breathing problems), general well-being (i.e., pain, dental concerns,
      sleep patterns, general stress level, fatigue), and any changes in medications, medical
      status, and employment will be collected utilizing the Follow-up Symptom & History
      Questionnaire. Telephone follow-up calls utilizing the Follow-up Symptom Assessment & History
      Questionnaire will be made on a monthly basis between the 60-day follow-up visit and the
      12-month endpoint visit. Should a subject develop symptoms potentially associated with
      COVID-19 infection at any point during the 12-month study period, that subject will be seen
      in the clinic by the Infectious Disease (ID) Co-investigator, and a repeat collection of
      blood and nasopharyngeal biospecimens will be performed for analysis, and the subject will be
      asked to complete the Follow-up Symptom & History Questionnaire and get another body
      composition analysis via BOD POD. Subjects will be asked to report the development of any
      potential COVID-19 infection-related symptoms or positive COVID-19 infection testing outside
      of the study, as well as any symptoms potentially related to MMR vaccination. Should a
      subject become admitted to the hospital related to COVID-19 infection, in-patient information
      will be obtained via the electronic medical record (EMR) when available.

      Primary outcome measures will be peripheral blood monocytic MDSCs (M-MDSC) and/or
      granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples.
      Specifically, documented increases in the MDSCs per subject from baseline through 30-60 days
      post-vaccination is expected in the MMR group compared to placebo group. Measles antibody are
      also expected to increase in the MMR group and will serve as a control for the MMR
      vaccination. Stationary levels of MDSCs and measles antibodies are expected in the MMR group
      over the 12-month period.

      The investigators will perform the COVID-19 RNA testing at baseline, 14, 30, and 60 days
      post-vaccination, and at any point over the 12-month period that symptoms arise. All patients
      that are COVID-19+ at baseline or become COVID-19+ through the study will be included for
      secondary outcome analyses. The Secondary outcome measures will be COVID-19 antibodies
      (seropositive) as evidence of infection, sepsis/lung inflammation, ICU/ventilator usage,
      in-patient health related co-morbidities and self-reporting mental status (such as general
      fatigue/stress level) over the 12-month period post-vaccination. In-patient information will
      be obtained through the EMR when available. Out-patient information will be obtained via
      self-reporting utilizing the Follow-up Symptom & History Questionnaire.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: MMR vaccine vs placebo
primary purpose: Prevention
masking: Single (Participant)
masking description: Randomized by study nurse
measure: Induction of myeloid-derived suppressor cells (MDSCs)
time frame: 14 days post-vaccination
description: peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline
measure: Induction of MDSCs
time frame: 30 days post vaccination
description: peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline
measure: Induction of MDSCs
time frame: 60 days post vaccination
description: peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline
measure: Induction of MDSCs
time frame: 12 months post vaccination
description: peripheral blood monocytic MDSCs (M-MDSC) and/or granulocytic MDSCs (G-MDSC) determined by flow cytometry from whole blood samples as percentage/fold increase over baseline
measure: COVID-19 infection positive
time frame: 14 days post-vaccination
description: COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection
measure: COVID-19 infection positive
time frame: 30 days post-vaccination
description: COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection
measure: COVID-19 infection positive
time frame: 60 days post-vaccination
description: COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection
measure: COVID-19 infection positive
time frame: 12 months post-vaccination
description: COVID-19 antibodies (seropositive) or COVID-19 RNA+ as evidence of infection
measure: Health questionnaire
time frame: 14 days post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 30 days post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 60 days post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 3 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 4 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 5 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 6 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 7 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 8 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 9 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 10 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 11 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
measure: Health questionnaire
time frame: 12 months post-vaccination
description: Sepsis/lung inflammation, ICU/ventilator usage, in-patient health related co-morbidities and self-reporting mental status (such as general fatigue/stress level)
arm group label: MMR vaccination
arm group type: Experimental
description: Subjects will be randomized to receive the MMR Vaccine subcutaneously
arm group label: Placebo control
arm group type: Placebo Comparator
description: Subjects will be randomized to receive sterile saline given subcutaneously
intervention type: Biological
intervention name: MMR vaccine
description: Merck MMR-II vaccine
arm group label: MMR vaccination
arm group label: Placebo control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Paul L Fidel, PhD
role: Principal Investigator
affiliation: Louisiana State University Health Sciences Center - New Orleans
facility: 
country: United States
citation: Fidel PL Jr, Noverr MC. Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection? mBio. 2020 Jun 19;11(3):e00907-20. doi: 10.1128/mBio.00907-20.
PMID: 32561657
responsible party type: Principal Investigator
investigator affiliation: Louisiana State University Health Sciences Center in New Orleans
investigator full name: Paul Fidel
investigator title: Professor and Associate Dean
mesh term: COVID-19
mesh term: Sepsis
mesh term: Toxemia
mesh term: Systemic Inflammatory Response Syndrome
sharing ipd: Yes
ipd description: We plan to share de-identified participant data to other researchers at their request and with justification. Primary and secondary outcome measures will be shared
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Informed Consent Form (ICF)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd time frame: 2 years
ipd access criteria: If fully justified for additional research purposes