<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/NCT04467047</url>
  </required_header>
  <id_info>
    <org_study_id>20200148</org_study_id>
    <nct_id>NCT04467047</nct_id>
  </id_info>
  <brief_title>Safety and Feasibility of Allogenic MSC in the Treatment of COVID-19</brief_title>
  <acronym>COVID19</acronym>
  <official_title>Safety and Feasibility of Allogenic Mesenchymal Stromal Cells in the Treatment of COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital de Clinicas de Porto Alegre</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hospital de Clinicas de Porto Alegre</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health&#xD;
      emergency of major international concern. Currently, no specific drugs or vaccines are&#xD;
      available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory&#xD;
      monocytes are rapidly activated and then producing a large number of cytokines and inducing&#xD;
      an inflammatory storm. Mesenchymal stem cells (MSCs) have been shown to possess a&#xD;
      comprehensive powerful immunomodulatory function. This study aims to investigate the safety&#xD;
      and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with&#xD;
      COVID-19.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Coronavirus-19 Disease (COVID-19), caused by the Sars-Cov-2 virus, which occurs as a growing&#xD;
      pandemic in early 2020 and currently represents an emergency state worldwide. Several reports&#xD;
      have shown that the first step in the pathogenesis of Sars-Cov-2 is the recognition of the&#xD;
      angiotensin I converting enzyme (ACE2) receptor by the virus. This ACE2 receptor is widely&#xD;
      distributed on the surface of human cells, especially as type II alveolar cells and capillary&#xD;
      endothelium, however bone marrow, lymph nodes, thymus and spleen are known as immune cells,&#xD;
      such as T and lymphocytes. B and macrophages, are negatives to ACE2. These results suggest&#xD;
      that immunotherapy can be used to treat infected patients. However, an immunomodulatory&#xD;
      capacity cannot be so strong, if just one or two major immunological factors used, as the&#xD;
      virus can cause a &quot;cytokine storm&quot;, such as IL-2, IL-6, IL-7, GSCF, IP10 , MCP1, MIP1A and&#xD;
      TNFα, followed by edema, gas exchange dysfunction, acute respiratory distress syndrome,&#xD;
      cardiac injury and secondary infection that can lead to death. Therefore, avoiding a&#xD;
      &quot;cytokine storm&quot; may be the key to treating patients infected with Sars-Cov-2. Mesenchymal&#xD;
      stem cells (MSCs), due to their potential for immunomodulatory activity, can have beneficial&#xD;
      effects in preventing or attenuating the cytokine storm. Because MSCs have been widely used&#xD;
      in cell therapy, from basic research to clinical trials. Safety and efficacy have been&#xD;
      clearly documented in several clinical trials, especially in immune-mediated inflammatory&#xD;
      diseases, such as graft versus host disease (GVHD). The objective of the study is to verify&#xD;
      the safety and feasibility of using allogeneic bone marrow mesenchymal stem cells in patients&#xD;
      with SARS-CoV-2.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 25, 2020</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall survival</measure>
    <time_frame>60 days</time_frame>
    <description>Assessment of Overall survival at 30 days post intervention</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes on inflammatory C-reactive protein</measure>
    <time_frame>60 days</time_frame>
    <description>To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of C-reactive protein (mg/dL)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital stay</measure>
    <time_frame>60 days</time_frame>
    <description>days of the patients in hospital</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Oxygenation index (PaO2/FiO2)</measure>
    <time_frame>60 days</time_frame>
    <description>Evaluation of functional respiratory changes: PaO2 / FiO2 ratio</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Improvement in Liao's score (2020)</measure>
    <time_frame>60 days</time_frame>
    <description>Improvement in Liao's score (2020)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiological improvement</measure>
    <time_frame>60 days</time_frame>
    <description>Computed tomography Chest assesment will be done to assess improvement in radiological findings of COVID-19</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of COVID19 PCR negativity</measure>
    <time_frame>28 days</time_frame>
    <description>PCR testing to check PCR negativity</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>COVID-19</condition>
  <condition>Sars-CoV2</condition>
  <arm_group>
    <arm_group_label>Intervention</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Mesenchymal Stromal Cells infusion</intervention_name>
    <description>Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion</description>
    <arm_group_label>Intervention</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Laboratory confirmation of COVID19 infection by reverse-transcription polymerase chain&#xD;
             reaction (RT-PCR)&#xD;
&#xD;
          -  The patient or legal donor agrees to participate in the study and signs the informed&#xD;
             consent.&#xD;
&#xD;
          -  Patients with orange or red criteria according to the score proposed by Liao et al&#xD;
             (2020)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patient with pregnancy, are planning to become pregnant or breastfeeding&#xD;
&#xD;
          -  Patients with malignant blood-borne diseases such as HIV or syphilis&#xD;
&#xD;
          -  Not consenting for clinical trial&#xD;
&#xD;
          -  Patients with other than orange or red criteria according to the score proposed by&#xD;
             Liao et al (2020)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lucia Silla, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital de Clinicas de Porto Alegre</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Lucia Silla, MD, PhD</last_name>
    <phone>55 51 33598371</phone>
    <email>lsilla@hcpa.edu.br</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Annelise Pezzi, PhD</last_name>
    <email>annepezzi@gmail.com</email>
  </overall_contact_backup>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 7, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 10, 2020</study_first_posted>
  <last_update_submitted>July 9, 2020</last_update_submitted>
  <last_update_submitted_qc>July 9, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 10, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Mesenchymal Stromal Cells</keyword>
  <keyword>COVID-19</keyword>
  <keyword>Sars-CoV2</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04467047
org study id: 20200148
nct id: NCT04467047
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Coronavirus Disease 2019 (COVID-19) is spreading worldwide and has become a public health
      emergency of major international concern. Currently, no specific drugs or vaccines are
      available. For severe cases, it was found that aberrant pathogenic T cells and inflammatory
      monocytes are rapidly activated and then producing a large number of cytokines and inducing
      an inflammatory storm. Mesenchymal stem cells (MSCs) have been shown to possess a
      comprehensive powerful immunomodulatory function. This study aims to investigate the safety
      and efficacy of intravenous infusion of mesenchymal stem cells in severe patients with
      COVID-19.
Coronavirus-19 Disease (COVID-19), caused by the Sars-Cov-2 virus, which occurs as a growing
      pandemic in early 2020 and currently represents an emergency state worldwide. Several reports
      have shown that the first step in the pathogenesis of Sars-Cov-2 is the recognition of the
      angiotensin I converting enzyme (ACE2) receptor by the virus. This ACE2 receptor is widely
      distributed on the surface of human cells, especially as type II alveolar cells and capillary
      endothelium, however bone marrow, lymph nodes, thymus and spleen are known as immune cells,
      such as T and lymphocytes. B and macrophages, are negatives to ACE2. These results suggest
      that immunotherapy can be used to treat infected patients. However, an immunomodulatory
      capacity cannot be so strong, if just one or two major immunological factors used, as the
      virus can cause a "cytokine storm", such as IL-2, IL-6, IL-7, GSCF, IP10 , MCP1, MIP1A and
      TNFα, followed by edema, gas exchange dysfunction, acute respiratory distress syndrome,
      cardiac injury and secondary infection that can lead to death. Therefore, avoiding a
      "cytokine storm" may be the key to treating patients infected with Sars-Cov-2. Mesenchymal
      stem cells (MSCs), due to their potential for immunomodulatory activity, can have beneficial
      effects in preventing or attenuating the cytokine storm. Because MSCs have been widely used
      in cell therapy, from basic research to clinical trials. Safety and efficacy have been
      clearly documented in several clinical trials, especially in immune-mediated inflammatory
      diseases, such as graft versus host disease (GVHD). The objective of the study is to verify
      the safety and feasibility of using allogeneic bone marrow mesenchymal stem cells in patients
      with SARS-CoV-2.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall survival
time frame: 60 days
description: Assessment of Overall survival at 30 days post intervention
measure: Changes on inflammatory C-reactive protein
time frame: 60 days
description: To assess the anti-inflammatory effect of the proposed treatment with assessment of the levels of C-reactive protein (mg/dL)
measure: Hospital stay
time frame: 60 days
description: days of the patients in hospital
measure: Oxygenation index (PaO2/FiO2)
time frame: 60 days
description: Evaluation of functional respiratory changes: PaO2 / FiO2 ratio
measure: Improvement in Liao's score (2020)
time frame: 60 days
description: Improvement in Liao's score (2020)
measure: Radiological improvement
time frame: 60 days
description: Computed tomography Chest assesment will be done to assess improvement in radiological findings of COVID-19
measure: Time of COVID19 PCR negativity
time frame: 28 days
description: PCR testing to check PCR negativity
arm group label: Intervention
arm group type: Experimental
description: Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion
intervention type: Biological
intervention name: Mesenchymal Stromal Cells infusion
description: Intravenous 1*10E6 MSCs/kg body weight Mesenchymal Stromal Cells infusion
arm group label: Intervention
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Lucia Silla, MD, PhD
role: Principal Investigator
affiliation: Hospital de Clinicas de Porto Alegre
last name: Lucia Silla, MD, PhD
phone: 55 51 33598371
email: lsilla@hcpa.edu.br
last name: Annelise Pezzi, PhD
email: annepezzi@gmail.com
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: No