<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/NCT03800277</url>
  </required_header>
  <id_info>
    <org_study_id>GASTRO-Phenulin (2016-317)</org_study_id>
    <nct_id>NCT03800277</nct_id>
  </id_info>
  <brief_title>Effect of Cranberry and Agaves Extract on Microbiota and Intestinal Health</brief_title>
  <acronym>Phenulin</acronym>
  <official_title>Prebiotic Supplementation and Metabolic Endotoxemia and Modulation of the Gut Microbiota: Double-blind and Randomized Parallel Clinical Study of the Efficacy and Synergistical Effect of Cranberry Polyphenols and Inulin From Agaves</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laval University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Ministry of Agriculture, Fisheries and Food, Quebec</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ministry of economic development, innovation and export trade, Quebec</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Diana Food, Symrise</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Atrium Innovations</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>NutriAgaves, Mexico</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Société des Produits Nestlé (SPN)</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Laval University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The growing prevalence of obesity and type 2 diabetes (T2D) is a major public health problem.&#xD;
      Recent studies have clearly established that the gut microbiota plays a key role in the&#xD;
      investigator's propensity to develop obesity and associated metabolic health disorders. The&#xD;
      gut microbiota compositions plays a decisive role in glucose metabolism and the chronic&#xD;
      inflammatory state associated with insulin resistance. Consuming prebiotic rich diet,&#xD;
      including polyphenol and inulin rich food could help modulate favorably the gut microbiota&#xD;
      which could lead to a reduction of endotoxemia and beneficial metabolic health effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is now recognized that overweight individuals have altered microbiota which could lead to&#xD;
      intestinal barrier defects and chronic inflammation disorders. Polyphenols such as&#xD;
      Proanthocyanidins may modulate the gut microbiota thereby providing beneficial effects on&#xD;
      metabolic health. Inulin is a well known prebiotic that could stimulate growth of favorable&#xD;
      bacteria in the gut.&#xD;
&#xD;
      The overall goal is to determine the efficacy and synergy of a supplement of polyphenols from&#xD;
      cranberry extract with or without a supplement of inulin from agaves to reduce chronic&#xD;
      inflammation and endotoxemia and to improve glucose metabolism and insulin sensitivity by&#xD;
      modulating microbiota of overweight human subjects with metabolic syndrome symptoms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 5, 2018</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</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>Prevention</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in metabolic endotoxemia: Measure concentration of Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP) in plasma</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on variation in plasma concentration of LPS and LBP</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in intestinal permeability: Measure concentration of zonulin in plasma</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on plasma concentration of zonulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in inflammation state of the tissue: Measure concentration of calprotectin and lactoferrin in feces</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on fecal calprotectin and lactoferrin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in systemic inflammation: Measure concentration of inflammation biomarkers in the serum</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on chronic inflammation (serum concentration of hsCRP, Il-6, TNF-alpha, IL-1 beta, IL-23)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in glucose serum concentration</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on serum concentration of glucose</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in insulin and C-peptide serum concentration</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>effect of the supplements on serum concentration of insulin and C-peptide</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in microbiota diversity: growth of Akkermancia muciniphila, Lactobacillus, Prevotella, Bifdobacterium and inhibition of Clostridium perfringens, C. difficile, Bacteroides spp.)</measure>
    <time_frame>At the beginning and the end of treatment (10 weeks)</time_frame>
    <description>Global variation of the fecal microbiota and gut microbiota profiling</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">122</enrollment>
  <condition>Endotoxemia</condition>
  <condition>Metabolic Syndrome</condition>
  <condition>Glucose Metabolism Disorders</condition>
  <condition>Insulin Resistance</condition>
  <arm_group>
    <arm_group_label>Cranberry and Agaves</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cranberry extract (2 capsules) + Agaves powder (1 single-dose packet)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cranberry and placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cranberry extract (2 capsules) + Placebo powder (1 single-dose packet)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and Agaves</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Placebo (2 capsules) + Agaves powder (1 single-dose packet)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo (2 capsules) + Placebo powder (1 single-dose packet)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Cranberry</intervention_name>
    <description>Supplementation of polyphenols from cranberry extract</description>
    <arm_group_label>Cranberry and Agaves</arm_group_label>
    <arm_group_label>Cranberry and placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Agaves</intervention_name>
    <description>Supplementation of inulin from Agaves powder</description>
    <arm_group_label>Cranberry and Agaves</arm_group_label>
    <arm_group_label>Placebo and Agaves</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Supplementation with placebo</description>
    <arm_group_label>Cranberry and placebo</arm_group_label>
    <arm_group_label>Placebo and Agaves</arm_group_label>
    <arm_group_label>Placebo and placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  overweight (BMI 25-39.9 kg/m2) or waist circumference ≥ 80 cm (women) and ≥94 cm (men)&#xD;
&#xD;
          -  fasting insulin over 60 pmol/L or fasting glucose 5.6 - 6.9 mmol/L&#xD;
&#xD;
          -  at least one of the following criteria: Tg ≥ 1.7 mmol/L; blood pressure ≥ 130/85 mmHg;&#xD;
             HDL &lt; 0,9 mmol/L; hsCRP 1-10 mg/L&#xD;
&#xD;
          -  non-smoking&#xD;
&#xD;
          -  eating fruits and vegetables less then 5 portions/day&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chronic disease&#xD;
&#xD;
          -  taking drugs or natural health products that could affect glucose or lipid metabolism&#xD;
&#xD;
          -  taking anti-inflammatory, antiacids&#xD;
&#xD;
          -  taking pre or probiotics&#xD;
&#xD;
          -  inflammatory bowel disease&#xD;
&#xD;
          -  antibiotics in the past 3 months&#xD;
&#xD;
          -  allergy or intolerance to cranberries or agaves&#xD;
&#xD;
          -  Major surgery in the past 3 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Hélène Jacques, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of nutrition and functional foods, Laval University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Yves Desjardins, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Institute of nutrition and functional foods, Laval University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of nutrition and functional foods, Laval University</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <zip>G1V 0A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>December 6, 2018</study_first_submitted>
  <study_first_submitted_qc>January 8, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 11, 2019</study_first_posted>
  <last_update_submitted>March 17, 2023</last_update_submitted>
  <last_update_submitted_qc>March 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laval University</investigator_affiliation>
    <investigator_full_name>Helene Jacques</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Endotoxemia</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Metabolic Diseases</mesh_term>
    <mesh_term>Glucose Metabolism Disorders</mesh_term>
  </condition_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/NCT03800277
org study id: GASTRO-Phenulin (2016-317)
nct id: NCT03800277
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
The growing prevalence of obesity and type 2 diabetes (T2D) is a major public health problem.
      Recent studies have clearly established that the gut microbiota plays a key role in the
      investigator's propensity to develop obesity and associated metabolic health disorders. The
      gut microbiota compositions plays a decisive role in glucose metabolism and the chronic
      inflammatory state associated with insulin resistance. Consuming prebiotic rich diet,
      including polyphenol and inulin rich food could help modulate favorably the gut microbiota
      which could lead to a reduction of endotoxemia and beneficial metabolic health effects.
It is now recognized that overweight individuals have altered microbiota which could lead to
      intestinal barrier defects and chronic inflammation disorders. Polyphenols such as
      Proanthocyanidins may modulate the gut microbiota thereby providing beneficial effects on
      metabolic health. Inulin is a well known prebiotic that could stimulate growth of favorable
      bacteria in the gut.

      The overall goal is to determine the efficacy and synergy of a supplement of polyphenols from
      cranberry extract with or without a supplement of inulin from agaves to reduce chronic
      inflammation and endotoxemia and to improve glucose metabolism and insulin sensitivity by
      modulating microbiota of overweight human subjects with metabolic syndrome symptoms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in metabolic endotoxemia: Measure concentration of Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP) in plasma
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on variation in plasma concentration of LPS and LBP
measure: Change in intestinal permeability: Measure concentration of zonulin in plasma
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on plasma concentration of zonulin
measure: Change in inflammation state of the tissue: Measure concentration of calprotectin and lactoferrin in feces
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on fecal calprotectin and lactoferrin
measure: Change in systemic inflammation: Measure concentration of inflammation biomarkers in the serum
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on chronic inflammation (serum concentration of hsCRP, Il-6, TNF-alpha, IL-1 beta, IL-23)
measure: Change in glucose serum concentration
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on serum concentration of glucose
measure: Change in insulin and C-peptide serum concentration
time frame: At the beginning and the end of treatment (10 weeks)
description: effect of the supplements on serum concentration of insulin and C-peptide
measure: Change in microbiota diversity: growth of Akkermancia muciniphila, Lactobacillus, Prevotella, Bifdobacterium and inhibition of Clostridium perfringens, C. difficile, Bacteroides spp.)
time frame: At the beginning and the end of treatment (10 weeks)
description: Global variation of the fecal microbiota and gut microbiota profiling
arm group label: Cranberry and Agaves
arm group type: Experimental
description: Cranberry extract (2 capsules) + Agaves powder (1 single-dose packet)
arm group label: Cranberry and placebo
arm group type: Experimental
description: Cranberry extract (2 capsules) + Placebo powder (1 single-dose packet)
arm group label: Placebo and Agaves
arm group type: Experimental
description: Placebo (2 capsules) + Agaves powder (1 single-dose packet)
arm group label: Placebo and placebo
arm group type: Placebo Comparator
description: Placebo (2 capsules) + Placebo powder (1 single-dose packet)
intervention type: Dietary Supplement
intervention name: Cranberry
description: Supplementation of polyphenols from cranberry extract
arm group label: Cranberry and Agaves
arm group label: Cranberry and placebo
intervention type: Dietary Supplement
intervention name: Agaves
description: Supplementation of inulin from Agaves powder
arm group label: Cranberry and Agaves
arm group label: Placebo and Agaves
intervention type: Dietary Supplement
intervention name: Placebo
description: Supplementation with placebo
arm group label: Cranberry and placebo
arm group label: Placebo and Agaves
arm group label: Placebo and placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Hélène Jacques, PhD
role: Principal Investigator
affiliation: Institute of nutrition and functional foods, Laval University
last name: Yves Desjardins, PhD
role: Study Director
affiliation: Institute of nutrition and functional foods, Laval University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Laval University
investigator full name: Helene Jacques
investigator title: Professor
mesh term: Endotoxemia
mesh term: Metabolic Syndrome
mesh term: Insulin Resistance
mesh term: Metabolic Diseases
mesh term: Glucose Metabolism Disorders