<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/NCT04420676</url>
  </required_header>
  <id_info>
    <org_study_id>SynCov</org_study_id>
    <nct_id>NCT04420676</nct_id>
  </id_info>
  <brief_title>Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection</brief_title>
  <acronym>SynCov</acronym>
  <official_title>Synbiotic Therapy of Gastrointestinal Symptoms During Covid-19 Infection: A Randomized, Double-blind, Placebo Controlled, Telemedicine Study (SynCov Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Graz</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Graz</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>
      We hypothesize that the intake of Omni-Biotic® 10 AAD can reduce intestinal inflammation and&#xD;
      improves dysbiosis in Covid-19 disease. We further hypothesize that Omni-Biotic® 10 AAD can&#xD;
      reduce the duration of diarrhea, stool frequency, improve stool consistency, improve other&#xD;
      gastrointestinal symptoms of Covid-19, reduce disease duration and severity.&#xD;
&#xD;
      The investigators aim to perform a randomized, double blind, placebo-controlled study using&#xD;
      telemedicine in patients with Covid-19 disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in&#xD;
      Wuhan, Hubei province in December 2019, spread throughout China in early 2020 and developed&#xD;
      as a pandemic thereafter. Although the virus mainly causes respiratory symptoms, GI&#xD;
      (gastrointestinal) presentations have been reported in and outside of China. Patients may&#xD;
      present with anorexia, nausea, vomiting, diarrhea and abdominal discomfort. Also, faecal-oral&#xD;
      transmission of the virus is currently discussed. Preliminary, unpublished data from China&#xD;
      suggest that patients with GI symptoms may suffer more frequently from severe courses of the&#xD;
      disease. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases.&#xD;
      It may precede or trail respiratory symptoms. A pooled analysis revealed an overall&#xD;
      percentage of diarrhea onset of 10.4%. SARS-CoV-2 uses the angiotensin-converting enzyme 2&#xD;
      (ACE2) for cellular entry. ACE2 is expressed in the small intestinal epithelia as well as in&#xD;
      the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly&#xD;
      higher (10-20 times) compared with SARS-CoV. Diarrhea is associated with prolonged symptoms&#xD;
      and viral carriage.&#xD;
&#xD;
      Clinical information on the characteristics of Covid-19 diarrhea is scarce. The duration of&#xD;
      diarrhea is around 4 days with 3-4 loose stools per day. Faecal calprotectin is elevated in&#xD;
      stool of patients with Covid-19 diarrhea, indicating a relation between gastrointestinal&#xD;
      symptoms and this well-established inflammation biomarker.&#xD;
&#xD;
      So far, no therapy is available for Covid-19 infection in general or for Covid-19 induced&#xD;
      diarrhea. Rehydration and potassium monitoring should be performed as in all patients with&#xD;
      diarrhea. It is important to underline that antivirals and antibiotics are often used for&#xD;
      COVID-19 treatment or treatment of bacterial superinfections, involving a likely alteration&#xD;
      of the gut microbiota and causing diarrhea. It is therefore plausible that the gut microbiota&#xD;
      could be a new therapeutic target and that probiotics or synbiotics (combination of&#xD;
      probiotics with prebiotics) could have a role in the management of these patients. The&#xD;
      China's National Health Commission recommended the use of probiotics for the treatment of&#xD;
      patients with severe COVID-19 in order to preserve intestinal balance and to prevent&#xD;
      secondary bacterial infections without any available clinical studies to support this and&#xD;
      probiotics apparently were used in Zhejiang during the Covid-19 pandemic. Although there is&#xD;
      no specific data on the effects of probiotics on SARS-CoV2 infections, meta-analyses show&#xD;
      that probiotics are effective in the treatment of upper respiratory tract infections and&#xD;
      viral gastroenteritis of other origins. Furthermore, Enterococcus faecium has been shown to&#xD;
      have antiviral effects in enteropathogenic coronavirus transmissible gastroenteritis virus&#xD;
      infections in piglets. We therefore aim to assess the role of synbiotics in the therapy of&#xD;
      Covid-19 infection with gastrointestinal symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 24, 2020</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Actual">December 1, 2021</primary_completion_date>
  <phase>N/A</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>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Stool calprotectin</measure>
    <time_frame>30 days</time_frame>
    <description>measured by ELISA</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stool frequency</measure>
    <time_frame>30 days</time_frame>
    <description>stool evacuations per days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool consistency</measure>
    <time_frame>30 days</time_frame>
    <description>Stool consistency according to Bristol stool scale for each evacuation, score 1-7, a higher score means a lower stool consistancy</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gastrointestinal symptoms</measure>
    <time_frame>30 days</time_frame>
    <description>presence of anorexia, nausea, vomiting, abdominal pain, bloating (yes/no)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Covid-19 disease</measure>
    <time_frame>30 days</time_frame>
    <description>days patients feel sick, are not able to work or are on sick leave</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of Covid-19 disease</measure>
    <time_frame>30 days</time_frame>
    <description>mild/moderate/severe</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Diarrhea</measure>
    <time_frame>30 days</time_frame>
    <description>3 or more stool evacuations, consistency Bristol stool scale 5-7</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stool Zonulin</measure>
    <time_frame>30 days</time_frame>
    <description>measured by ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiome composition</measure>
    <time_frame>30 days</time_frame>
    <description>16S RNA sequencing</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>COVID</condition>
  <arm_group>
    <arm_group_label>Probiotic</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Group 1: receiving a probiotic mixture (Omni-Biotic® 10 AAD) twice a day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Group 2: receiving a similar looking and tasting placebo without bacteria twice a day</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Omnibiotic AAD</intervention_name>
    <description>Bacterial strains in Omni-Biotic® 10 AAD are Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus plantarum W1, Lactobacillus plantarum W62, Lactobacillus rhamnosus W71 and Lactobacillus salivarius W24 which are embedded in a matrix containing maize starch, maltodextrin, inulin, potassium chloride, hydrolysed rice protein, magnesium sulphate, fructooligosaccharide (FOS), enzymes (amylases), vanilla flavour and manganese sulphate</description>
    <arm_group_label>Probiotic</arm_group_label>
    <other_name>Ecologic AAD</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>matrix containing maize starch, maltodextrin, inulin, potassium chloride, hydrolysed rice protein, magnesium sulphate, fructooligosaccharide (FOS), enzymes (amylases), vanilla flavour and manganese sulphate.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  Covid-19 infection diagnosed by a positive SARS-Cov-2 PCR (Polymerase chain reaction)&#xD;
             result from a nasopharyngeal swab&#xD;
&#xD;
          -  Informed (tele)consent Exclusion criteria&#xD;
&#xD;
          -  Pre-existing diarrhoea (including but not restricted to chronic inflammatory bowel&#xD;
             disease, chronic diarrhea of other causes, acute diarrheal illness -4 to -1 week&#xD;
             before inclusion)&#xD;
&#xD;
          -  Antibiotic therapy -4 to -1 week before inclusion&#xD;
&#xD;
          -  Probiotic treatment -4 to -1 week before inclusion&#xD;
&#xD;
          -  Technical difficulties to perform telemedicine study visits&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Department of Internal Medicine, Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <zip>8010</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 4, 2020</study_first_submitted>
  <study_first_submitted_qc>June 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>January 23, 2023</last_update_submitted>
  <last_update_submitted_qc>January 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>Yes</sharing_ipd>
    <ipd_description>Upload of microbiome sequences and metadata to a repository</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_time_frame>1 year after completion</ipd_time_frame>
    <ipd_access_criteria>free</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/NCT04420676
org study id: SynCov
nct id: NCT04420676
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
We hypothesize that the intake of Omni-Biotic® 10 AAD can reduce intestinal inflammation and
      improves dysbiosis in Covid-19 disease. We further hypothesize that Omni-Biotic® 10 AAD can
      reduce the duration of diarrhea, stool frequency, improve stool consistency, improve other
      gastrointestinal symptoms of Covid-19, reduce disease duration and severity.

      The investigators aim to perform a randomized, double blind, placebo-controlled study using
      telemedicine in patients with Covid-19 disease.
The outbreak of the novel coronavirus (SARS-CoV-2)-infected disease (COVID-19) began in
      Wuhan, Hubei province in December 2019, spread throughout China in early 2020 and developed
      as a pandemic thereafter. Although the virus mainly causes respiratory symptoms, GI
      (gastrointestinal) presentations have been reported in and outside of China. Patients may
      present with anorexia, nausea, vomiting, diarrhea and abdominal discomfort. Also, faecal-oral
      transmission of the virus is currently discussed. Preliminary, unpublished data from China
      suggest that patients with GI symptoms may suffer more frequently from severe courses of the
      disease. Clinical studies show an incidence rate of diarrhea ranging from 2% to 50% of cases.
      It may precede or trail respiratory symptoms. A pooled analysis revealed an overall
      percentage of diarrhea onset of 10.4%. SARS-CoV-2 uses the angiotensin-converting enzyme 2
      (ACE2) for cellular entry. ACE2 is expressed in the small intestinal epithelia as well as in
      the upper esophagus, liver, and colon. SARS-CoV-2 binding affinity to ACE2 is significantly
      higher (10-20 times) compared with SARS-CoV. Diarrhea is associated with prolonged symptoms
      and viral carriage.

      Clinical information on the characteristics of Covid-19 diarrhea is scarce. The duration of
      diarrhea is around 4 days with 3-4 loose stools per day. Faecal calprotectin is elevated in
      stool of patients with Covid-19 diarrhea, indicating a relation between gastrointestinal
      symptoms and this well-established inflammation biomarker.

      So far, no therapy is available for Covid-19 infection in general or for Covid-19 induced
      diarrhea. Rehydration and potassium monitoring should be performed as in all patients with
      diarrhea. It is important to underline that antivirals and antibiotics are often used for
      COVID-19 treatment or treatment of bacterial superinfections, involving a likely alteration
      of the gut microbiota and causing diarrhea. It is therefore plausible that the gut microbiota
      could be a new therapeutic target and that probiotics or synbiotics (combination of
      probiotics with prebiotics) could have a role in the management of these patients. The
      China's National Health Commission recommended the use of probiotics for the treatment of
      patients with severe COVID-19 in order to preserve intestinal balance and to prevent
      secondary bacterial infections without any available clinical studies to support this and
      probiotics apparently were used in Zhejiang during the Covid-19 pandemic. Although there is
      no specific data on the effects of probiotics on SARS-CoV2 infections, meta-analyses show
      that probiotics are effective in the treatment of upper respiratory tract infections and
      viral gastroenteritis of other origins. Furthermore, Enterococcus faecium has been shown to
      have antiviral effects in enteropathogenic coronavirus transmissible gastroenteritis virus
      infections in piglets. We therefore aim to assess the role of synbiotics in the therapy of
      Covid-19 infection with gastrointestinal symptoms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Stool calprotectin
time frame: 30 days
description: measured by ELISA
measure: Stool frequency
time frame: 30 days
description: stool evacuations per days
measure: Stool consistency
time frame: 30 days
description: Stool consistency according to Bristol stool scale for each evacuation, score 1-7, a higher score means a lower stool consistancy
measure: Gastrointestinal symptoms
time frame: 30 days
description: presence of anorexia, nausea, vomiting, abdominal pain, bloating (yes/no)
measure: Duration of Covid-19 disease
time frame: 30 days
description: days patients feel sick, are not able to work or are on sick leave
measure: Severity of Covid-19 disease
time frame: 30 days
description: mild/moderate/severe
measure: Diarrhea
time frame: 30 days
description: 3 or more stool evacuations, consistency Bristol stool scale 5-7
measure: Stool Zonulin
time frame: 30 days
description: measured by ELISA
measure: Microbiome composition
time frame: 30 days
description: 16S RNA sequencing
arm group label: Probiotic
arm group type: Active Comparator
description: Group 1: receiving a probiotic mixture (Omni-Biotic® 10 AAD) twice a day
arm group label: Placebo
arm group type: Placebo Comparator
description: Group 2: receiving a similar looking and tasting placebo without bacteria twice a day
intervention type: Dietary Supplement
intervention name: Omnibiotic AAD
description: Bacterial strains in Omni-Biotic® 10 AAD are Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W37, Lactobacillus acidophilus W55, Lactobacillus paracasei W20, Lactobacillus plantarum W1, Lactobacillus plantarum W62, Lactobacillus rhamnosus W71 and Lactobacillus salivarius W24 which are embedded in a matrix containing maize starch, maltodextrin, inulin, potassium chloride, hydrolysed rice protein, magnesium sulphate, fructooligosaccharide (FOS), enzymes (amylases), vanilla flavour and manganese sulphate
arm group label: Probiotic
other name: Ecologic AAD
intervention type: Dietary Supplement
intervention name: Placebo
description: matrix containing maize starch, maltodextrin, inulin, potassium chloride, hydrolysed rice protein, magnesium sulphate, fructooligosaccharide (FOS), enzymes (amylases), vanilla flavour and manganese sulphate.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Austria
responsible party type: Sponsor
mesh term: COVID-19
sharing ipd: Yes
ipd description: Upload of microbiome sequences and metadata to a repository
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd time frame: 1 year after completion
ipd access criteria: free