<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/NCT04460638</url>
  </required_header>
  <id_info>
    <org_study_id>2020-COVID19-15</org_study_id>
    <secondary_id>2020-A01249-30</secondary_id>
    <nct_id>NCT04460638</nct_id>
  </id_info>
  <brief_title>SARS-CoV2 (COVID-19) Diagnosis in Human Saliva by MALDI-TOF MS Profiling</brief_title>
  <acronym>CoviDiagMS</acronym>
  <official_title>SARS-CoV2 (COVID-19) Diagnosis in Human Saliva by MALDI-TOF MS Profiling</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Direction Centrale du Service de Santé des Armées</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Direction Centrale du Service de Santé des Armées</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Since March 2020, SARS-CoV2 virus (nCoV19; COVID-19) is considered pandemic. Its high rate of&#xD;
      spread and infection in the human population and the lack of effective and validated&#xD;
      treatment have led the authorities of several countries to confine their populations to slow&#xD;
      the spread of COVID-19. As part of the management of this health crisis, the screening of&#xD;
      individuals is essential in order to isolate &quot;infected cases&quot;. These screening tests are&#xD;
      currently performed on nasopharyngeal swabs using RT-PCR for the detection of viral RNA.&#xD;
      Although sensitive and specific, these tests remain relatively long (2-5 hours), expensive&#xD;
      and the strong international demand for nucleic extraction kits and enzymes are factors&#xD;
      limiting the implementation of widespread screening (problem of supply of swabs, molecular&#xD;
      biology consumables).&#xD;
&#xD;
      In order to prevent the risks of a shortage of screening means, we propose to develop an&#xD;
      innovative alternative strategy, PCR-free, based on the detection of specific protein&#xD;
      signatures in human saliva by MALDI-TOF MS profiling. MALDI-TOF MS profiling is a method used&#xD;
      in routine diagnostics by microbiology laboratories for the identification of microorganisms.&#xD;
      MALDI-TOF MS profiling has been successfully used to classify individuals according to their&#xD;
      infectious status (oral pathologies) based on the analysis of their saliva, but also as a&#xD;
      tool for the identification of respiratory viruses from cell culture supernatants. In&#xD;
      addition, we have expertise and skills in the field of MALDI-TOF MS profiling and have&#xD;
      implemented new strategies to improve the quality of profiles and their analysis,&#xD;
      particularly in the context of entomological and vector identification projects. Finally,&#xD;
      recent Chinese studies have reported that COVID-19 was detectable in saliva by RT-PCR.&#xD;
&#xD;
      The main objective of this study is to develop a test based on the MALDI-TOF profiling method&#xD;
      to detect individuals infected with SARS-CoV2 from saliva sample.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 23, 2020</start_date>
  <completion_date type="Actual">August 13, 2021</completion_date>
  <primary_completion_date type="Actual">August 13, 2021</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Development of a test based on the MALDI-TOF profiling method to detect individuals infected with SARS-CoV2 from saliva sample.</measure>
    <time_frame>Day 30</time_frame>
    <description>The development of this test is based on machine learning techniques, which involve &quot;training&quot; a mathematical model, in which the results of the mass spectrometry analysis of saliva samples and clinical data will be used to determine the information needed to distinguish a saliva sample from a SARS-CoV2-infected participant from a healthy saliva sample.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of correct classification by the test (MALDI-TOF MS profiling) from saliva sample</measure>
    <time_frame>Day 30</time_frame>
    <description>For each saliva sample, the status (&quot;correct&quot; or &quot;incorrect&quot;) of the classification of the sample (&quot;infected&quot; or &quot;not infected&quot;) by the test (MALDI-TOF MS profiling) will be determined. Then the rate of correct classification will be calculated. The test will be considered efficient when it has reached a correct classification rate of more than 95%.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rate of correct classification by RT-PCR from saliva sample</measure>
    <time_frame>Day 30</time_frame>
    <description>For each saliva sample, the status (&quot;correct&quot; or &quot;incorrect&quot;) of the classification of the sample (&quot;infected&quot; or &quot;not infected&quot;) by RT-PCR will be determined. Then the rate of correct classification by RT-PCR will be calculated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Identification of proteins specific to the SARS-CoV2 infection</measure>
    <time_frame>Day 30</time_frame>
    <description>On each saliva sample, the expression of proteins will be determined using mass spectrometry. By comparison between SARS-CoV2 infected saliva samples and non-infected saliva samples, the presence of proteins that are specifically expressed in SARS-CoV2 infected saliva samples will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Presence of a positive anti-SARS-CoV2 antibody response by RT-PCR</measure>
    <time_frame>Day 30</time_frame>
    <description>On each SARS-CoV2 infected saliva sample, the presence of anti-SARS-CoV2 antibodies, by RT-PCR, will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Correlation between the identified protein markers and the clinical course of the participants.</measure>
    <time_frame>Day 30</time_frame>
    <description>In SARS-CoV2 infected participants (Covid+ hospitalization group and Covid+ outpatient group), the presence of a correlation between the presence of proteins specific to the SARS-CoV2 infection and the clinical evolution of patients will be determined.</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">779</enrollment>
  <condition>SARS-CoV 2</condition>
  <arm_group>
    <arm_group_label>Covid+ hospitalization group</arm_group_label>
    <description>Patients hospitalized with SARS-CoV2 infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Covid+ outpatient group</arm_group_label>
    <description>Patients or caregivers followed on an outpatient basis for an SARS-CoV2 infection</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Covid- group</arm_group_label>
    <description>Caregivers not infected with an SARS-CoV2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-SARS pathology group</arm_group_label>
    <description>Individuals not infected with SARS-CoV2 but with another acute and/or infectious non-SARS pathology</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Saliva collection</intervention_name>
    <description>Saliva samples are regularly collected over a period of up to 30 consecutive days.</description>
    <arm_group_label>Covid+ hospitalization group</arm_group_label>
    <arm_group_label>Covid+ outpatient group</arm_group_label>
    <arm_group_label>Covid- group</arm_group_label>
    <arm_group_label>Non-SARS pathology group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Clinical assessment</intervention_name>
    <description>The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.</description>
    <arm_group_label>Covid+ hospitalization group</arm_group_label>
    <arm_group_label>Covid+ outpatient group</arm_group_label>
    <arm_group_label>Covid- group</arm_group_label>
    <arm_group_label>Non-SARS pathology group</arm_group_label>
  </intervention>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Saliva samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        The study population consists of patients and caregivers infected and uninfected with&#xD;
        CoV2-SARS.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age;&#xD;
&#xD;
          -  screened for SARS-CoV2 by RT-PCR from a nasopharyngeal swab within 96 hours prior to&#xD;
             inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient admitted to intensive care;&#xD;
&#xD;
          -  Pregnant woman.&#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>
  <location>
    <facility>
      <name>Hôpital d'Instruction des Armées Laveran</name>
      <address>
        <city>Marseille</city>
        <zip>13013</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>July 6, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>September 4, 2023</last_update_submitted>
  <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MALDI-TOF MS</keyword>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04460638
org study id: 2020-COVID19-15
secondary id: 2020-A01249-30
nct id: NCT04460638
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Since March 2020, SARS-CoV2 virus (nCoV19; COVID-19) is considered pandemic. Its high rate of
      spread and infection in the human population and the lack of effective and validated
      treatment have led the authorities of several countries to confine their populations to slow
      the spread of COVID-19. As part of the management of this health crisis, the screening of
      individuals is essential in order to isolate "infected cases". These screening tests are
      currently performed on nasopharyngeal swabs using RT-PCR for the detection of viral RNA.
      Although sensitive and specific, these tests remain relatively long (2-5 hours), expensive
      and the strong international demand for nucleic extraction kits and enzymes are factors
      limiting the implementation of widespread screening (problem of supply of swabs, molecular
      biology consumables).

      In order to prevent the risks of a shortage of screening means, we propose to develop an
      innovative alternative strategy, PCR-free, based on the detection of specific protein
      signatures in human saliva by MALDI-TOF MS profiling. MALDI-TOF MS profiling is a method used
      in routine diagnostics by microbiology laboratories for the identification of microorganisms.
      MALDI-TOF MS profiling has been successfully used to classify individuals according to their
      infectious status (oral pathologies) based on the analysis of their saliva, but also as a
      tool for the identification of respiratory viruses from cell culture supernatants. In
      addition, we have expertise and skills in the field of MALDI-TOF MS profiling and have
      implemented new strategies to improve the quality of profiles and their analysis,
      particularly in the context of entomological and vector identification projects. Finally,
      recent Chinese studies have reported that COVID-19 was detectable in saliva by RT-PCR.

      The main objective of this study is to develop a test based on the MALDI-TOF profiling method
      to detect individuals infected with SARS-CoV2 from saliva sample.
observational model: Cohort
time perspective: Prospective
measure: Development of a test based on the MALDI-TOF profiling method to detect individuals infected with SARS-CoV2 from saliva sample.
time frame: Day 30
description: The development of this test is based on machine learning techniques, which involve "training" a mathematical model, in which the results of the mass spectrometry analysis of saliva samples and clinical data will be used to determine the information needed to distinguish a saliva sample from a SARS-CoV2-infected participant from a healthy saliva sample.
measure: Rate of correct classification by the test (MALDI-TOF MS profiling) from saliva sample
time frame: Day 30
description: For each saliva sample, the status ("correct" or "incorrect") of the classification of the sample ("infected" or "not infected") by the test (MALDI-TOF MS profiling) will be determined. Then the rate of correct classification will be calculated. The test will be considered efficient when it has reached a correct classification rate of more than 95%.
measure: Rate of correct classification by RT-PCR from saliva sample
time frame: Day 30
description: For each saliva sample, the status ("correct" or "incorrect") of the classification of the sample ("infected" or "not infected") by RT-PCR will be determined. Then the rate of correct classification by RT-PCR will be calculated.
measure: Identification of proteins specific to the SARS-CoV2 infection
time frame: Day 30
description: On each saliva sample, the expression of proteins will be determined using mass spectrometry. By comparison between SARS-CoV2 infected saliva samples and non-infected saliva samples, the presence of proteins that are specifically expressed in SARS-CoV2 infected saliva samples will be determined.
measure: Presence of a positive anti-SARS-CoV2 antibody response by RT-PCR
time frame: Day 30
description: On each SARS-CoV2 infected saliva sample, the presence of anti-SARS-CoV2 antibodies, by RT-PCR, will be determined.
measure: Correlation between the identified protein markers and the clinical course of the participants.
time frame: Day 30
description: In SARS-CoV2 infected participants (Covid+ hospitalization group and Covid+ outpatient group), the presence of a correlation between the presence of proteins specific to the SARS-CoV2 infection and the clinical evolution of patients will be determined.
arm group label: Covid+ hospitalization group
description: Patients hospitalized with SARS-CoV2 infection
arm group label: Covid+ outpatient group
description: Patients or caregivers followed on an outpatient basis for an SARS-CoV2 infection
arm group label: Covid- group
description: Caregivers not infected with an SARS-CoV2
arm group label: Non-SARS pathology group
description: Individuals not infected with SARS-CoV2 but with another acute and/or infectious non-SARS pathology
intervention type: Biological
intervention name: Saliva collection
description: Saliva samples are regularly collected over a period of up to 30 consecutive days.
arm group label: Covid+ hospitalization group
arm group label: Covid+ outpatient group
arm group label: Covid- group
arm group label: Non-SARS pathology group
intervention type: Other
intervention name: Clinical assessment
description: The participant's clinical data will be collected regularly over a period of up to 30 consecutive days.
arm group label: Covid+ hospitalization group
arm group label: Covid+ outpatient group
arm group label: Covid- group
arm group label: Non-SARS pathology group
Saliva samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: France
responsible party type: Sponsor
sharing ipd: Undecided