<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/NCT03815786</url>
  </required_header>
  <id_info>
    <org_study_id>XUANRO4-NATURE 3.1</org_study_id>
    <nct_id>NCT03815786</nct_id>
  </id_info>
  <brief_title>NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins</brief_title>
  <acronym>NATURE31</acronym>
  <official_title>XUANRO4 - NATURE 3.1 - Nuovo Approccio Per la Riduzione Delle Tossine Uremiche Renali, REGIONE PUGLIA FSC 2007-2013 Ricerca. Intervento Cluster Tecnologici Regionali</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Bari Aldo Moro</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari</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>
      The objective of the pilot study is to validate the clinical use of an innovative symbiotic&#xD;
      in patients with chronic kidney disease (CKD) stage 3b-4 and in healthy subjects.&#xD;
&#xD;
      The study aims at evaluating the effects of a symbiotic, consisting of a mixture of&#xD;
      probiotics (Lactobacilli and Bifidobacteria), prebiotics (fructooligosaccharides and inulin)&#xD;
      and natural antioxidants (a mix of quercetin, resveratrol and proanthocyanidins), by&#xD;
      achieving two objectives:&#xD;
&#xD;
        1. Reduction of the serum levels of microbiota-derived uremic toxins, involved in a variety&#xD;
           of cardiovascular complications in CKD&#xD;
&#xD;
        2. Reduction of intestinal permeability, inflammatory markers and oxidative stress&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 24, 2017</start_date>
  <completion_date type="Actual">October 17, 2017</completion_date>
  <primary_completion_date type="Actual">October 17, 2017</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change of serum concentration of pCS</measure>
    <time_frame>3 months</time_frame>
    <description>Change of p-cresyl sulfate (pCS) serum concentrations assessed by liquid chromatography/mass spectrometry</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change of serum concentration of IS</measure>
    <time_frame>3 months</time_frame>
    <description>Change of indoxyl sulfate (IS) serum concentrations assessed by liquid chromatography/mass spectrometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of serum concentration of D-lactate</measure>
    <time_frame>3 months</time_frame>
    <description>Change of D-lactate serum concentration (uM)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of serum concentration of LPS</measure>
    <time_frame>3 months</time_frame>
    <description>Change of lipopolysaccharide (LPS) serum concentration (EU/ml)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of percentage of sugar urinary recovery</measure>
    <time_frame>3 months</time_frame>
    <description>Change of percentage (%) of urinary recovery of 4 sugars (lactulose, mannitol, sucrose and sucralose)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of serum concentration of inflammatory markers</measure>
    <time_frame>3 months</time_frame>
    <description>Change of interleukin (IL)6, IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change of serum concentration of NO</measure>
    <time_frame>3 months</time_frame>
    <description>Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Gut microbiota</measure>
    <time_frame>3 months</time_frame>
    <description>Change of the relative abundance (%) of Operational Taxonomic Units (OTUs) of Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Synergistetes, Cyanobacteria, Euryarchaeota, Chloroflexi, Nitrospirae, Tenericutes, Fusobacteria, Thermotogae, Acidobacteria evaluated by fecal bacterial DNA genome sequencing.</description>
  </other_outcome>
  <other_outcome>
    <measure>Change of GI symptoms</measure>
    <time_frame>3 months</time_frame>
    <description>Change of gastrointestinal symptoms evaluated by Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire (15 items scored 0-3 each, 0 representing the best and 3 the worse outcome for each item)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change of stool type</measure>
    <time_frame>3 months</time_frame>
    <description>Change of stool type evaluated by BRISTOL Stool Scale (range 1-7, lower and higher values representing worse outcome, middle values representing better outcome)</description>
  </other_outcome>
  <other_outcome>
    <measure>Change of serum concentration of TMAO</measure>
    <time_frame>3 months</time_frame>
    <description>Change of trimethylamine-N-oxide (TMAO) serum concentrations assessed by liquid chromatography/mass spectrometry</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">50</enrollment>
  <condition>Chronic Kidney Diseases</condition>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>CKD patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>CKD patients stage 3b-4 will follow a 2-months supplementation of either symbiotic or placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Controls</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Healthy volunteers will follow a 2-months supplementation of either symbiotic or placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Symbiotic</intervention_name>
    <description>2-months oral administration of the symbiotic supplement (2 bags/day) + 1 month washout</description>
    <arm_group_label>CKD patients</arm_group_label>
    <arm_group_label>Controls</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>2-months oral administration of the placebo (2 bags/day) + 1 month washout</description>
    <arm_group_label>CKD patients</arm_group_label>
    <arm_group_label>Controls</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        CKD patients&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  CKD patients stage 3b-4 not on dialysis&#xD;
&#xD;
          -  Aged between 30 to 65&#xD;
&#xD;
          -  BMI between 18.5 and 29.9&#xD;
&#xD;
          -  Controlled diet&#xD;
&#xD;
          -  Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes mellitus&#xD;
&#xD;
          -  Use of antibiotics or probiotics up to 30 days prior to recruitment&#xD;
&#xD;
          -  Chronic gastrointestinal disorders&#xD;
&#xD;
          -  Systemic inflammatory diseases&#xD;
&#xD;
          -  Suspicion or clinical diagnosis of malignancy&#xD;
&#xD;
          -  Chronic liver disease&#xD;
&#xD;
          -  Treatment with corticosteroids or immunosuppressive drugs&#xD;
&#xD;
          -  Previous acute cardiovascular diseases (myocardial infarction, stroke)&#xD;
&#xD;
          -  Psychiatric conditions reducing the compliance to treatment protocols&#xD;
&#xD;
        Healthy volunteers&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy subjects&#xD;
&#xD;
          -  Aged between 35 to 60&#xD;
&#xD;
          -  BMI between 18.5 and 29.9&#xD;
&#xD;
          -  Medium score of adherence to Mediterranean Diet (PREDIMED score between 6 and 9)&#xD;
&#xD;
          -  Informed consent signed&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Type 2 diabetes mellitus&#xD;
&#xD;
          -  Use of antibiotics or probiotics up to 30 days prior to recruitment&#xD;
&#xD;
          -  Chronic gastrointestinal disorders&#xD;
&#xD;
          -  Systemic inflammatory diseases&#xD;
&#xD;
          -  Suspicion or clinical diagnosis of malignancy&#xD;
&#xD;
          -  Chronic liver disease&#xD;
&#xD;
          -  Treatment with corticosteroids or immunosuppressive drugs&#xD;
&#xD;
          -  Previous acute cardiovascular diseases (myocardial infarction, stroke)&#xD;
&#xD;
          -  Psychiatric conditions reducing the compliance to treatment protocols&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Loreto Gesualdo, MD Full Prof</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nephrology, Dialysis and Transplantation Unit &quot;Aldo Moro&quot; University of Bari</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>AUO Policlinico Consorziale</name>
      <address>
        <city>Bari</city>
        <state>BA</state>
        <zip>70125</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 23, 2018</study_first_submitted>
  <study_first_submitted_qc>January 21, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>February 1, 2022</last_update_submitted>
  <last_update_submitted_qc>February 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 15, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>gut microbiota dysbiosis</keyword>
  <keyword>uremic toxins</keyword>
  <keyword>symbiotic</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Renal Insufficiency, Chronic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03815786
org study id: XUANRO4-NATURE 3.1
nct id: NCT03815786
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The objective of the pilot study is to validate the clinical use of an innovative symbiotic
      in patients with chronic kidney disease (CKD) stage 3b-4 and in healthy subjects.

      The study aims at evaluating the effects of a symbiotic, consisting of a mixture of
      probiotics (Lactobacilli and Bifidobacteria), prebiotics (fructooligosaccharides and inulin)
      and natural antioxidants (a mix of quercetin, resveratrol and proanthocyanidins), by
      achieving two objectives:

        1. Reduction of the serum levels of microbiota-derived uremic toxins, involved in a variety
           of cardiovascular complications in CKD

        2. Reduction of intestinal permeability, inflammatory markers and oxidative stress
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Change of serum concentration of pCS
time frame: 3 months
description: Change of p-cresyl sulfate (pCS) serum concentrations assessed by liquid chromatography/mass spectrometry
measure: Change of serum concentration of IS
time frame: 3 months
description: Change of indoxyl sulfate (IS) serum concentrations assessed by liquid chromatography/mass spectrometry
measure: Change of serum concentration of D-lactate
time frame: 3 months
description: Change of D-lactate serum concentration (uM)
measure: Change of serum concentration of LPS
time frame: 3 months
description: Change of lipopolysaccharide (LPS) serum concentration (EU/ml)
measure: Change of percentage of sugar urinary recovery
time frame: 3 months
description: Change of percentage (%) of urinary recovery of 4 sugars (lactulose, mannitol, sucrose and sucralose)
measure: Change of serum concentration of inflammatory markers
time frame: 3 months
description: Change of interleukin (IL)6, IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA
measure: Change of serum concentration of NO
time frame: 3 months
description: Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry
measure: Gut microbiota
time frame: 3 months
description: Change of the relative abundance (%) of Operational Taxonomic Units (OTUs) of Firmicutes, Bacteroidetes, Proteobacteria, Verrucomicrobia, Actinobacteria, Synergistetes, Cyanobacteria, Euryarchaeota, Chloroflexi, Nitrospirae, Tenericutes, Fusobacteria, Thermotogae, Acidobacteria evaluated by fecal bacterial DNA genome sequencing.
measure: Change of GI symptoms
time frame: 3 months
description: Change of gastrointestinal symptoms evaluated by Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire (15 items scored 0-3 each, 0 representing the best and 3 the worse outcome for each item)
measure: Change of stool type
time frame: 3 months
description: Change of stool type evaluated by BRISTOL Stool Scale (range 1-7, lower and higher values representing worse outcome, middle values representing better outcome)
measure: Change of serum concentration of TMAO
time frame: 3 months
description: Change of trimethylamine-N-oxide (TMAO) serum concentrations assessed by liquid chromatography/mass spectrometry
arm group label: CKD patients
arm group type: Experimental
description: CKD patients stage 3b-4 will follow a 2-months supplementation of either symbiotic or placebo
arm group label: Controls
arm group type: Other
description: Healthy volunteers will follow a 2-months supplementation of either symbiotic or placebo
intervention type: Dietary Supplement
intervention name: Symbiotic
description: 2-months oral administration of the symbiotic supplement (2 bags/day) + 1 month washout
arm group label: CKD patients
arm group label: Controls
intervention type: Dietary Supplement
intervention name: Placebo
description: 2-months oral administration of the placebo (2 bags/day) + 1 month washout
arm group label: CKD patients
arm group label: Controls
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Loreto Gesualdo, MD Full Prof
role: Principal Investigator
affiliation: Nephrology, Dialysis and Transplantation Unit "Aldo Moro" University of Bari
facility: 
country: Italy
responsible party type: Sponsor
mesh term: Kidney Diseases
mesh term: Renal Insufficiency, Chronic
sharing ipd: Undecided