<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/NCT04427865</url>
  </required_header>
  <id_info>
    <org_study_id>CUKA-002</org_study_id>
    <nct_id>NCT04427865</nct_id>
  </id_info>
  <brief_title>Utility of Lactoferrin as a Preventive Agent for Healthcare Workers Exposed to COVID-19</brief_title>
  <official_title>Efficacy of Lactoferrin as a Preventive Agent for Healthcare Workers Exposed to COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cairo University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cairo University</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>
      COVID 19, which probably started from zoonotic transmission related to crowded markets in&#xD;
      China was announced as a pandemic by the WHO on 11 March 2020.&#xD;
&#xD;
      There is currently no clinically proven specific antiviral agents available for SARS-CoV-2&#xD;
      infection. Supportive treatment, including oxygen therapy, fluid management, and&#xD;
      broad-spectrum antibiotics to cover secondary bacterial infection, remains the most important&#xD;
      management strategy.&#xD;
&#xD;
      Since its discovery, lactoferrin and its related peptides are considered non-specific host&#xD;
      defense molecules against a broad range of viruses including SARS-CoV, which is closely&#xD;
      related to SARS-CoV-2 that causes COVID-19. Besides reducing viral entry, lactoferrin can&#xD;
      also suppress virus replication after the viral entry and has an immunomodulatory effect that&#xD;
      can prevent the cytokine storm associated with COVID-19.&#xD;
&#xD;
      The aim of our study is to assess the safety and efficacy of lactoferrin within the context&#xD;
      of SARS-CoV-2 and propose the possibility of supplemental lactoferrin as a potential&#xD;
      preventive drug for healthcare workers exposed to SARS-CoV-2.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In December, 2019, an outbreak of pneumonia with unknown cause occurred in Wuhan city, in&#xD;
      China. On January 7th, the scientists succeeded to isolate a novel coronavirus, severe acute&#xD;
      respiratory syndrome coronavirus 2 (SARS-CoV-2). WHO nominated it as coronavirus disease 2019&#xD;
      (COVID-19) in February, 2020. COVID-19 has a wide clinical spectrum ranging between&#xD;
      asymptomatic infection, mild upper respiratory tract symptoms, and severe viral pneumonia&#xD;
      that may result in respiratory failure and finally death. There is currently no clinically&#xD;
      proven specific antiviral agent available for SARS-CoV-2 infection. Supportive treatment,&#xD;
      including oxygen therapy, conservation fluid management, and broad-spectrum antibiotics to&#xD;
      cover secondary bacterial infection, remains the most important management strategy.&#xD;
&#xD;
      Lactoferrin is a highly conserved pleiotropic iron-binding 80-kDa glycoprotein of the&#xD;
      transferrin family that is expressed and secreted by glandular cells and found in most body&#xD;
      fluids with especially high concentrations in mammalian milk. Since its discovery,&#xD;
      lactoferrin and its related peptides are mainly considered to be important non-specific host&#xD;
      defense molecules against a broad range of viruses including SARS-CoV, which is closely&#xD;
      related to SARS-CoV-2 that causes COVID-19. Lactoferrin has been found to experimentally&#xD;
      inhibit viral entry in murine coronavirus, and human coronaviruses hCOV-NL63 and pseudotyped&#xD;
      SARS-CoV. Given the homology of SARS-CoV and SARS-CoV-2 spike protein structures, as well as&#xD;
      both viruses depending on the same ACE2 receptor for cell entry, it is likely that&#xD;
      lactoferrin can inhibit SARS-CoV-2 invasion as in the case of SARS-CoV. Besides reducing&#xD;
      viral entry, lactoferrin can also suppress virus replication after the viral entry as in the&#xD;
      case of HIV.&#xD;
&#xD;
      Another major aspect of lactoferrin bioactivity relates to its immunomodulatory and&#xD;
      anti-inflammatory functions. Current thinking suggests that mortality from COVID-19 is not&#xD;
      simply due to viral infection but is a result of a cytokine storm associated with&#xD;
      hyper-inflammation leading to acute respiratory distress and subsequent mortality. A cytokine&#xD;
      profile in severe COVID-19 cases is characterized by increases in cytokines and acute phase&#xD;
      reactants such as interleukin IL-6, tumor necrosis factor-a (TNFa) and ferritin. In this&#xD;
      regard, lactoferrin was demonstrated to reduce IL-6, TNF a, and downregulate ferritin in&#xD;
      experimental settings simulating sepsis.&#xD;
&#xD;
      In this study, we aim to study the antiviral properties and immunomodulatory mechanisms of&#xD;
      lactoferrin within the context of its potential applications against SARS-CoV-2 and propose&#xD;
      the possibility of supplemental lactoferrin as a potential preventive agent for COVID-19.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 2020</start_date>
  <completion_date type="Anticipated">November 2020</completion_date>
  <primary_completion_date type="Anticipated">September 2020</primary_completion_date>
  <phase>Phase 2/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>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of SARS-CoV-2</measure>
    <time_frame>28 days</time_frame>
    <description>Number of confirmed infections of SARS-CoV-2 in healthcare workers</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Severity of disease in confirmed infected participants</measure>
    <time_frame>28 days</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>COVID-19</condition>
  <arm_group>
    <arm_group_label>Lactoferrin prophylaxis</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>200 mg oral lactoferrin daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>prophylactic lactoferrin daily</intervention_name>
    <description>200 mg oral lactoferrin daily</description>
    <arm_group_label>Lactoferrin prophylaxis</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  health care workers at risk of SARS-CoV-2 transmission with no previous diagnosis of&#xD;
             SARS-CoV-2 infection&#xD;
&#xD;
          -  No symptoms compatible with SARS-CoV-2 (COVID-19) until the date of enrolment in the&#xD;
             study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known allergy or hypersensitivity to the used medications&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 11, 2020</study_first_posted>
  <last_update_submitted>June 11, 2020</last_update_submitted>
  <last_update_submitted_qc>June 11, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Cairo University</investigator_affiliation>
    <investigator_full_name>Gamal Esmat</investigator_full_name>
    <investigator_title>Professor of Endemic Medicine</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lactoferrin</mesh_term>
  </intervention_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/NCT04427865
org study id: CUKA-002
nct id: NCT04427865
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
COVID 19, which probably started from zoonotic transmission related to crowded markets in
      China was announced as a pandemic by the WHO on 11 March 2020.

      There is currently no clinically proven specific antiviral agents available for SARS-CoV-2
      infection. Supportive treatment, including oxygen therapy, fluid management, and
      broad-spectrum antibiotics to cover secondary bacterial infection, remains the most important
      management strategy.

      Since its discovery, lactoferrin and its related peptides are considered non-specific host
      defense molecules against a broad range of viruses including SARS-CoV, which is closely
      related to SARS-CoV-2 that causes COVID-19. Besides reducing viral entry, lactoferrin can
      also suppress virus replication after the viral entry and has an immunomodulatory effect that
      can prevent the cytokine storm associated with COVID-19.

      The aim of our study is to assess the safety and efficacy of lactoferrin within the context
      of SARS-CoV-2 and propose the possibility of supplemental lactoferrin as a potential
      preventive drug for healthcare workers exposed to SARS-CoV-2.
In December, 2019, an outbreak of pneumonia with unknown cause occurred in Wuhan city, in
      China. On January 7th, the scientists succeeded to isolate a novel coronavirus, severe acute
      respiratory syndrome coronavirus 2 (SARS-CoV-2). WHO nominated it as coronavirus disease 2019
      (COVID-19) in February, 2020. COVID-19 has a wide clinical spectrum ranging between
      asymptomatic infection, mild upper respiratory tract symptoms, and severe viral pneumonia
      that may result in respiratory failure and finally death. There is currently no clinically
      proven specific antiviral agent available for SARS-CoV-2 infection. Supportive treatment,
      including oxygen therapy, conservation fluid management, and broad-spectrum antibiotics to
      cover secondary bacterial infection, remains the most important management strategy.

      Lactoferrin is a highly conserved pleiotropic iron-binding 80-kDa glycoprotein of the
      transferrin family that is expressed and secreted by glandular cells and found in most body
      fluids with especially high concentrations in mammalian milk. Since its discovery,
      lactoferrin and its related peptides are mainly considered to be important non-specific host
      defense molecules against a broad range of viruses including SARS-CoV, which is closely
      related to SARS-CoV-2 that causes COVID-19. Lactoferrin has been found to experimentally
      inhibit viral entry in murine coronavirus, and human coronaviruses hCOV-NL63 and pseudotyped
      SARS-CoV. Given the homology of SARS-CoV and SARS-CoV-2 spike protein structures, as well as
      both viruses depending on the same ACE2 receptor for cell entry, it is likely that
      lactoferrin can inhibit SARS-CoV-2 invasion as in the case of SARS-CoV. Besides reducing
      viral entry, lactoferrin can also suppress virus replication after the viral entry as in the
      case of HIV.

      Another major aspect of lactoferrin bioactivity relates to its immunomodulatory and
      anti-inflammatory functions. Current thinking suggests that mortality from COVID-19 is not
      simply due to viral infection but is a result of a cytokine storm associated with
      hyper-inflammation leading to acute respiratory distress and subsequent mortality. A cytokine
      profile in severe COVID-19 cases is characterized by increases in cytokines and acute phase
      reactants such as interleukin IL-6, tumor necrosis factor-a (TNFa) and ferritin. In this
      regard, lactoferrin was demonstrated to reduce IL-6, TNF a, and downregulate ferritin in
      experimental settings simulating sepsis.

      In this study, we aim to study the antiviral properties and immunomodulatory mechanisms of
      lactoferrin within the context of its potential applications against SARS-CoV-2 and propose
      the possibility of supplemental lactoferrin as a potential preventive agent for COVID-19.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: None (Open Label)
measure: Incidence of SARS-CoV-2
time frame: 28 days
description: Number of confirmed infections of SARS-CoV-2 in healthcare workers
measure: Severity of disease in confirmed infected participants
time frame: 28 days
arm group label: Lactoferrin prophylaxis
arm group type: Experimental
description: 200 mg oral lactoferrin daily
arm group label: Control group
arm group type: No Intervention
intervention type: Drug
intervention name: prophylactic lactoferrin daily
description: 200 mg oral lactoferrin daily
arm group label: Lactoferrin prophylaxis
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
responsible party type: Principal Investigator
investigator affiliation: Cairo University
investigator full name: Gamal Esmat
investigator title: Professor of Endemic Medicine
mesh term: COVID-19
mesh term: Lactoferrin