<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/NCT04468139</url>
  </required_header>
  <id_info>
    <org_study_id>20-95M</org_study_id>
    <nct_id>NCT04468139</nct_id>
  </id_info>
  <brief_title>The Study of Quadruple Therapy Zinc, Quercetin, Bromelain and Vitamin C on the Clinical Outcomes of Patients Infected With COVID-19</brief_title>
  <official_title>The Study of Quadruple Therapy Zinc, Quercetin, Bromelain and Vitamin C on the Clinical Outcomes of Patients Infected With COVID-19</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Ministry of Health, Saudi Arabia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Ministry of Health, Saudi Arabia</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      There are currently no antiviral drugs with proven efficacy nor are there vaccines for its&#xD;
      prevention. Unfortunately, the scientific community has little knowledge of the molecular&#xD;
      details of SARS-CoV-2 infection. The drugs we are chosen are used as clinical trials for&#xD;
      antiviral and there is no proven guide for specificity and effectiveness against the virus so&#xD;
      the results are different Now the clinical trials and research authorities are work speedily&#xD;
      to target the most proven treatment for the virus so anything is infantile until now. the&#xD;
      covid-19 with time be more explained by scientists it is steroid response disease and cause&#xD;
      thromosis and cytokine storm , the aim of the study to inhibit viral replication and decrease&#xD;
      the severity of the disease as antiviral and anticytokine storm , antithrombosis Zinc is a&#xD;
      mineral element needed to regulate adaptive immune cells' functions. Higher level of&#xD;
      intracellular zinc showed to increase intracellular pH; which affect on RNA-dependent RNA&#xD;
      polymerase and decrease replication mechanism of RNA viruses. Therefore, drugs that described&#xD;
      as zinc ionophores could be used with zinc supplement to act as antiviral against many RNA&#xD;
      viruses including SARS-CoV-2 Quercetin is natural compound act as zinc ionophore to cause&#xD;
      zinc influx intracellular.&#xD;
&#xD;
      Quercetin is a safe natural anti-oxidant and anti-inflammatory polyphenolic compound that&#xD;
      found in various natural sources include onion, red grapes, honey and citrus fruits. It was&#xD;
      shown that quercetin has the ability to chelate zinc ions and act as zinc ionophore.&#xD;
      Therefore, quercetin could have antiviral activity against many RNA viruses . Quercetin, a&#xD;
      flavonoid found in fruits and vegetables, has unique biological properties that may improve&#xD;
      mental/physical performance and reduce infection risk ; These properties form the basis for&#xD;
      potential benefits to overall health and disease resistance, including anti-carcinogenic,&#xD;
      anti-inflammatory, antiviral, antioxidant, and psychostimulant activities, as well as the&#xD;
      ability to inhibit lipid peroxidation, platelet aggregation and capillary permeability, and&#xD;
      to stimulate mitochondrial biogenesis .There are various studies that report the&#xD;
      immunomodulatory effect of bromelain . Bromelain activates natural killer cells and augments&#xD;
      the production of granulocyte-macrophage-colony stimulating factor, IL-2, IL-6 and decreases&#xD;
      the activation of Thelper cells. Thus, bromelain decreases the majority of inflammatory&#xD;
      mediators and has demonstrated a significant role as an anti-inflammatory agent in various&#xD;
      conditions Vitamin C is known as an essential anti-oxidant.,and enzymatic co-factor for&#xD;
      physiological reactions such as hormone production, collagen synthesis and immune&#xD;
      potentiation . Naturally, an insufficiency of vitamin C leads to severe injuries to multiple&#xD;
      organs, especially to the heart and brain, since they are both highly aerobic organs that&#xD;
      produce more oxygen radicals. In fact, studies of in vivo effect on vitamin C are difficult&#xD;
      since most animals, except human and some primate, are capable of synthesizing vitamin C&#xD;
      endogenously&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">June 20, 2020</start_date>
  <completion_date type="Anticipated">July 30, 2020</completion_date>
  <primary_completion_date type="Anticipated">July 20, 2020</primary_completion_date>
  <phase>Phase 4</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>days of stay at hospital after treatment and discharge</measure>
    <time_frame>28 days</time_frame>
    <description>speed the days of recovery and discharge from hospital</description>
  </primary_outcome>
  <primary_outcome>
    <measure>serum zinc before and after treatment</measure>
    <time_frame>5-10 days</time_frame>
    <description>the level of serum zinc is very important especially at chronic diseases</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>questionnaire including parameters like BMI,,smoking , underling diseases, immunological treatment ,</measure>
    <time_frame>28 days</time_frame>
    <description>according to questionnaire including BMI, smoking , underlying diseases like hypertension, diabetes , asthmatic , ..etc</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>day of negative conversion for nasopharyngeal swab for rt-PCR FOR covid-19</measure>
    <time_frame>28 days</time_frame>
    <description>day of negative conversion for nasopharyngeal swab for rt-PCR FOR covid-19</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Covid-19</condition>
  <arm_group>
    <arm_group_label>Quercetin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Quercetin 500 g of quercetin Quercetin will be administered orally once daily, in the morning before breakfast for 5-10 days or patient improves or discharged</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Quercetin</intervention_name>
    <description>Dietary Supplement: Quercetin Treatment a daily dose of quercetin (500 mg) will be taken orally by proven COVID-19 cases intervention</description>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>bromelain</intervention_name>
    <description>Dietary Supplement:Bromealin Treatment a daily dose of bromelain(500 mg) will be taken orally by proven COVID-19 cases intervention</description>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Zinc</intervention_name>
    <description>zinc 50 mg orally daily dose will be taken orally by proven COVID-19 cases intervention</description>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin C</intervention_name>
    <description>vitamin c 1000 mg orally daily by proven COVID-19 cases intervention</description>
    <arm_group_label>Quercetin</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 years&#xD;
&#xD;
          2. positive confirmed PCR covid-19&#xD;
&#xD;
          3. moderate to severe cases&#xD;
&#xD;
          4. obtained consent&#xD;
&#xD;
          5. must be able to swallow tablets&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who live outside Saudia Arabia&#xD;
&#xD;
          2. Pregnant women: Current known pregnancy positive pregnancy test.&#xD;
&#xD;
          3. Lactating women.&#xD;
&#xD;
          4. Documented allergy to pineapple or to quercetin&#xD;
&#xD;
          5. Documented history of mental illnesses&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hiba Hamadelnil elsaeed</last_name>
    <role>Study Director</role>
    <affiliation>Netherlands: Ministry of Health, Welfare and Sports</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>amr ahmed</last_name>
    <phone>00966597310032</phone>
    <email>drmedahmed@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>abdullah Alqattan</last_name>
    <phone>00966540745588</phone>
    <email>abdullahalkattan@gmail.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ministry of health.First health cluster ,Riaydh</name>
      <address>
        <city>Riyadh</city>
        <country>Saudi Arabia</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>yousef albalawi</last_name>
      <phone>00966542460550</phone>
      <email>dryousef37@gmail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Saudi Arabia</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 5, 2020</study_first_submitted>
  <study_first_submitted_qc>July 9, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 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 13, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Ministry of Health, Saudi Arabia</investigator_affiliation>
    <investigator_full_name>Amr kamel khalil Ahmed</investigator_full_name>
    <investigator_title>director of mobile team tuberculosis ghubera, tuberculosis control program</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>Quercetin</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/NCT04468139
org study id: 20-95M
nct id: NCT04468139
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
There are currently no antiviral drugs with proven efficacy nor are there vaccines for its
      prevention. Unfortunately, the scientific community has little knowledge of the molecular
      details of SARS-CoV-2 infection. The drugs we are chosen are used as clinical trials for
      antiviral and there is no proven guide for specificity and effectiveness against the virus so
      the results are different Now the clinical trials and research authorities are work speedily
      to target the most proven treatment for the virus so anything is infantile until now. the
      covid-19 with time be more explained by scientists it is steroid response disease and cause
      thromosis and cytokine storm , the aim of the study to inhibit viral replication and decrease
      the severity of the disease as antiviral and anticytokine storm , antithrombosis Zinc is a
      mineral element needed to regulate adaptive immune cells' functions. Higher level of
      intracellular zinc showed to increase intracellular pH; which affect on RNA-dependent RNA
      polymerase and decrease replication mechanism of RNA viruses. Therefore, drugs that described
      as zinc ionophores could be used with zinc supplement to act as antiviral against many RNA
      viruses including SARS-CoV-2 Quercetin is natural compound act as zinc ionophore to cause
      zinc influx intracellular.

      Quercetin is a safe natural anti-oxidant and anti-inflammatory polyphenolic compound that
      found in various natural sources include onion, red grapes, honey and citrus fruits. It was
      shown that quercetin has the ability to chelate zinc ions and act as zinc ionophore.
      Therefore, quercetin could have antiviral activity against many RNA viruses . Quercetin, a
      flavonoid found in fruits and vegetables, has unique biological properties that may improve
      mental/physical performance and reduce infection risk ; These properties form the basis for
      potential benefits to overall health and disease resistance, including anti-carcinogenic,
      anti-inflammatory, antiviral, antioxidant, and psychostimulant activities, as well as the
      ability to inhibit lipid peroxidation, platelet aggregation and capillary permeability, and
      to stimulate mitochondrial biogenesis .There are various studies that report the
      immunomodulatory effect of bromelain . Bromelain activates natural killer cells and augments
      the production of granulocyte-macrophage-colony stimulating factor, IL-2, IL-6 and decreases
      the activation of Thelper cells. Thus, bromelain decreases the majority of inflammatory
      mediators and has demonstrated a significant role as an anti-inflammatory agent in various
      conditions Vitamin C is known as an essential anti-oxidant.,and enzymatic co-factor for
      physiological reactions such as hormone production, collagen synthesis and immune
      potentiation . Naturally, an insufficiency of vitamin C leads to severe injuries to multiple
      organs, especially to the heart and brain, since they are both highly aerobic organs that
      produce more oxygen radicals. In fact, studies of in vivo effect on vitamin C are difficult
      since most animals, except human and some primate, are capable of synthesizing vitamin C
      endogenously
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: days of stay at hospital after treatment and discharge
time frame: 28 days
description: speed the days of recovery and discharge from hospital
measure: serum zinc before and after treatment
time frame: 5-10 days
description: the level of serum zinc is very important especially at chronic diseases
measure: questionnaire including parameters like BMI,,smoking , underling diseases, immunological treatment ,
time frame: 28 days
description: according to questionnaire including BMI, smoking , underlying diseases like hypertension, diabetes , asthmatic , ..etc
measure: day of negative conversion for nasopharyngeal swab for rt-PCR FOR covid-19
time frame: 28 days
description: day of negative conversion for nasopharyngeal swab for rt-PCR FOR covid-19
arm group label: Quercetin
arm group type: Experimental
description: Quercetin 500 g of quercetin Quercetin will be administered orally once daily, in the morning before breakfast for 5-10 days or patient improves or discharged
intervention type: Drug
intervention name: Quercetin
description: Dietary Supplement: Quercetin Treatment a daily dose of quercetin (500 mg) will be taken orally by proven COVID-19 cases intervention
arm group label: Quercetin
intervention type: Dietary Supplement
intervention name: bromelain
description: Dietary Supplement:Bromealin Treatment a daily dose of bromelain(500 mg) will be taken orally by proven COVID-19 cases intervention
arm group label: Quercetin
intervention type: Drug
intervention name: Zinc
description: zinc 50 mg orally daily dose will be taken orally by proven COVID-19 cases intervention
arm group label: Quercetin
intervention type: Drug
intervention name: Vitamin C
description: vitamin c 1000 mg orally daily by proven COVID-19 cases intervention
arm group label: Quercetin
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Hiba Hamadelnil elsaeed
role: Study Director
affiliation: Netherlands: Ministry of Health, Welfare and Sports
last name: amr ahmed
phone: 00966597310032
email: drmedahmed@gmail.com
last name: abdullah Alqattan
phone: 00966540745588
email: abdullahalkattan@gmail.com
facility: 
status: Recruiting
contact: 
country: Saudi Arabia
responsible party type: Principal Investigator
investigator affiliation: Ministry of Health, Saudi Arabia
investigator full name: Amr kamel khalil Ahmed
investigator title: director of mobile team tuberculosis ghubera, tuberculosis control program
mesh term: COVID-19
mesh term: Quercetin