<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/NCT03236090</url>
  </required_header>
  <id_info>
    <org_study_id>IIBSP-VIV-2016-109</org_study_id>
    <nct_id>NCT03236090</nct_id>
  </id_info>
  <brief_title>Effect of Vivomixx® on Neuroinflammation in Patients Withs Cirrhosis</brief_title>
  <official_title>Study of the Effect of Vivomixx® on Neuroinflammation Ans Systemic Inflammatory Response in Patients With Cirrhosis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Spanish Clinical Research Network - SCReN</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Study Design:&#xD;
&#xD;
      Double-blind randomized placebo-controlled clinical trial&#xD;
&#xD;
      Study Duration:&#xD;
&#xD;
      2 years&#xD;
&#xD;
      Study Center:&#xD;
&#xD;
      Single center Hospital de la Santa Creu i Sant Pau, Barcelona&#xD;
&#xD;
      Objectives:&#xD;
&#xD;
      To assess the effect of Vivomixx® on neuroinflammation and systemic inflammatory response in&#xD;
      patients with cirrhosis&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Study variables Main variables&#xD;
&#xD;
        -  Neuroinflammation&#xD;
&#xD;
        -  Systemic inflammatory response Secondary variables&#xD;
&#xD;
        -  Cognitive function&#xD;
&#xD;
        -  Bacterial translocation&#xD;
&#xD;
        -  Intestinal barrier&#xD;
&#xD;
        -  Systemic oxidative damage&#xD;
&#xD;
        -  Time until SBP or other bacterial infection resolution in patients with infections&#xD;
&#xD;
        -  Incidence of complications of cirrhosis and mortality during the study 40 patients, 20&#xD;
           and 30 in each of the two substudies, respectively Diagnosis and Main Inclusion Criteria&#xD;
&#xD;
        -  Decompensated patients with cirrhosis:&#xD;
&#xD;
             1. Outpatients with refractory ascites (substudy 1) (n=20)&#xD;
&#xD;
             2. Patients hospitalized because bacterial infection (substudy 2) (n=30)&#xD;
&#xD;
      Study Product:&#xD;
&#xD;
      Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)&#xD;
&#xD;
      Duration of administration:&#xD;
&#xD;
      30 days Follow up The following patients' assessments will be performed: in substudy 1 at&#xD;
      baseline and at the end of the treatment (30 days), and in substudy 2 at baseline, on day 1,&#xD;
      day 2, day 3, day 7, at infection resolution, and at discharge or day 30.&#xD;
&#xD;
      Clinical and analytical assessments will be performed every three months after the end of the&#xD;
      study Comparator Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in&#xD;
      addition to the standard of care) Statistical Methodology Fisher's exact test for categorical&#xD;
      variables and Student's &quot;t&quot; test and Mann-Whitney and Wilcoxon tests for quantitative&#xD;
      variables. Correlations will be assessed by Spearman test. A two-sided p value &lt;0.05 will be&#xD;
      considered statistically significant&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Problems to recruit patients due to exclusion criteria&#xD;
  </why_stopped>
  <start_date type="Actual">July 15, 2017</start_date>
  <completion_date type="Actual">March 9, 2018</completion_date>
  <primary_completion_date type="Actual">March 9, 2018</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>
    <intervention_model_description>Decompensated patients with cirrhosis:&#xD;
Outpatients with refractory ascites (substudy 1) (n=20)&#xD;
Patients hospitalized because bacterial infection (substudy 2) (n=30)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Single (Participant)</masking>
    <masking_description>Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in addition to the standard of care)</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in neuroinflammation</measure>
    <time_frame>Change from baseline at 30 days</time_frame>
    <description>For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in neuroinflammation</measure>
    <time_frame>Change from baseline at 3 days</time_frame>
    <description>For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Cirrhosis, Liver</condition>
  <arm_group>
    <arm_group_label>Outpatients with refractory ascites</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 consecutive outpatients with cirrhosis and refractory ascites Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Patients hospitalized because bacterial infection</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>30 consecutive patients with cirrhosis and bacterial infections. All patients will receive endovenous antibiotics and, only in the case of patients with SBP, also intravenous albumin Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Vivomixx</intervention_name>
    <description>Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)</description>
    <arm_group_label>Outpatients with refractory ascites</arm_group_label>
    <arm_group_label>Patients hospitalized because bacterial infection</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Outpatients with cirrhosis and refractory ascites according to current definition (29)&#xD;
             (substudy 1), and hospitalized patients with cirrhosis and an episode of bacterial&#xD;
             infection (substudy 2) at Hospital de la Santa Creu i Sant Pau.&#xD;
&#xD;
        Cirrhosis will be diagnosed by clinical, analytical and ultrasonographic findings or by&#xD;
        liver biopsy. SBP will be diagnosed by an ascitic fluid neutrophil count &gt; 250/mm3 with or&#xD;
        without positive culture (28). Bacteremia, urinary infections, pneumonia, cellulitis, other&#xD;
        bacterial infections and possible or suspected infections will be diagnosed according to&#xD;
        current guidelines (13,14,28). All patients with SBP, bacteremia or pneumonia will be&#xD;
        included. However patients with urinary infections, cellulitis or suspected infection these&#xD;
        non-SBP infections will be required to fulfil the following requirements: at least two&#xD;
        criteria of SIRS (systemic inflammatory response syndrome) (Annex I) (30) and CRP&#xD;
        (C-reactive protein) &gt;= 10 mg/dl (28).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Advanced hepatocellular carcinoma (beyond Milan's criteria) or any other malignancy&#xD;
             determining a poor short-term prognosis.&#xD;
&#xD;
          -  Advanced liver insufficiency [MELD (model for end-stage liver disease) &gt;25].&#xD;
&#xD;
          -  Marked symptomatic comorbidities (neurological, cardiac, pulmonary, renal,&#xD;
             psychiatric, HIV infection).&#xD;
&#xD;
          -  Septic shock, ileus, need for tracheal intubation or intensive care unit.&#xD;
&#xD;
          -  Immunomodulatory drugs.&#xD;
&#xD;
          -  In substudy 1, any infection at inclusion in the study.&#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>Hospital de la Santa Creu i Sant Pau</name>
      <address>
        <city>Barcelona</city>
        <zip>08025</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
  </location_countries>
  <verification_date>March 2018</verification_date>
  <study_first_submitted>June 29, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 1, 2017</study_first_posted>
  <last_update_submitted>March 12, 2018</last_update_submitted>
  <last_update_submitted_qc>March 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">March 13, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cirrhosis</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Systemic inflammation</keyword>
  <keyword>neuroinflammation</keyword>
  <keyword>Cognitive function</keyword>
  <keyword>Bacterial translocation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liver Cirrhosis</mesh_term>
    <mesh_term>Neuroinflammatory Diseases</mesh_term>
    <mesh_term>Fibrosis</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/NCT03236090
org study id: IIBSP-VIV-2016-109
nct id: NCT03236090
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
Study Design:

      Double-blind randomized placebo-controlled clinical trial

      Study Duration:

      2 years

      Study Center:

      Single center Hospital de la Santa Creu i Sant Pau, Barcelona

      Objectives:

      To assess the effect of Vivomixx® on neuroinflammation and systemic inflammatory response in
      patients with cirrhosis
Study variables Main variables

        -  Neuroinflammation

        -  Systemic inflammatory response Secondary variables

        -  Cognitive function

        -  Bacterial translocation

        -  Intestinal barrier

        -  Systemic oxidative damage

        -  Time until SBP or other bacterial infection resolution in patients with infections

        -  Incidence of complications of cirrhosis and mortality during the study 40 patients, 20
           and 30 in each of the two substudies, respectively Diagnosis and Main Inclusion Criteria

        -  Decompensated patients with cirrhosis:

             1. Outpatients with refractory ascites (substudy 1) (n=20)

             2. Patients hospitalized because bacterial infection (substudy 2) (n=30)

      Study Product:

      Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)

      Duration of administration:

      30 days Follow up The following patients' assessments will be performed: in substudy 1 at
      baseline and at the end of the treatment (30 days), and in substudy 2 at baseline, on day 1,
      day 2, day 3, day 7, at infection resolution, and at discharge or day 30.

      Clinical and analytical assessments will be performed every three months after the end of the
      study Comparator Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in
      addition to the standard of care) Statistical Methodology Fisher's exact test for categorical
      variables and Student's "t" test and Mann-Whitney and Wilcoxon tests for quantitative
      variables. Correlations will be assessed by Spearman test. A two-sided p value <0.05 will be
      considered statistically significant
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Decompensated patients with cirrhosis:
Outpatients with refractory ascites (substudy 1) (n=20)
Patients hospitalized because bacterial infection (substudy 2) (n=30)
primary purpose: Treatment
masking: Single (Participant)
masking description: Placebo (we evaluate the probiotic Vivomixx® vs placebo as adjunctive in addition to the standard of care)
measure: Change in neuroinflammation
time frame: Change from baseline at 30 days
description: For substudy 1, neuroinflammation will be measured by MRI at baseline and 30 days
measure: Change in neuroinflammation
time frame: Change from baseline at 3 days
description: For substudy 2, neuroinflammation will be measured by MRI at baseline and 3 days
arm group label: Outpatients with refractory ascites
arm group type: Active Comparator
description: 20 consecutive outpatients with cirrhosis and refractory ascites Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)
arm group label: Patients hospitalized because bacterial infection
arm group type: Active Comparator
description: 30 consecutive patients with cirrhosis and bacterial infections. All patients will receive endovenous antibiotics and, only in the case of patients with SBP, also intravenous albumin Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)
intervention type: Dietary Supplement
intervention name: Vivomixx
description: Vivomixx®sachets containing 450 x 109 bacteria, 2 every 12 hours (n=25), or placebo (n=25)
arm group label: Outpatients with refractory ascites
arm group label: Patients hospitalized because bacterial infection
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Spain
responsible party type: Sponsor
mesh term: Liver Cirrhosis
mesh term: Neuroinflammatory Diseases
mesh term: Fibrosis
sharing ipd: No