<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/NCT03754504</url>
  </required_header>
  <id_info>
    <org_study_id>MICA 2018-146</org_study_id>
    <nct_id>NCT03754504</nct_id>
  </id_info>
  <brief_title>Effects of Cranberry Powder Supplements on Gut Microbiota Diversity and Metabolic Syndrome</brief_title>
  <acronym>MICA</acronym>
  <official_title>Evaluation of the Effect of Cranberry Whole Fruit Powder on Gut Microbiota Diversity, Intestinal Health and Metabolic Syndrome in Overweight Individuals: a Proof-of-concept Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laval University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Naturex</agency>
      <agency_class>Other</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      It is of major importance to refine prevention strategies in order to alleviate inflammation,&#xD;
      insulin resistance and metabolic syndrome and it appear that improving gut health and&#xD;
      microbiota represent a promising strategy. Cranberry-enriched diets may help prevent&#xD;
      metabolic syndrome and its associated chronic diseases by a protective effect of gut health&#xD;
      and microbiota. It is therefore highly relevant to test the hypothesis that a whole cranberry&#xD;
      powder supplements (which include a mixture of polyphenols, free and fiber-associated&#xD;
      proanthocyanidins, and fruits fibers) is associated with changes on the gut health and&#xD;
      microbiota playing a major role in alleviating inflammation and obesity-associated metabolic&#xD;
      disorders.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Over the past decade it has become clear that the gut microbiota is a key determinant of&#xD;
      obesity and that its perturbations by nutritional insults play a significant role in the&#xD;
      development of metabolic complications such as insulin resistance, type 2 diabetes,&#xD;
      cardiovascular diseases and non-alcoholic fatty liver disease. Indeed, there is growing&#xD;
      amounts of studies that have shown that dysbiosis of the intestinal microbiota promotes&#xD;
      obesity-linked chronic inflammation, and is causally related to diet-induced type 2 diabetes.&#xD;
      Our group recently published that a polyphenol-rich cranberry extract exert striking effect&#xD;
      on the gut microbiota of high-fat and high-sucrose fed mice, which was associated with&#xD;
      prevention of diet-induced weight gain, visceral obesity, insulin resistance and hepatic&#xD;
      steatosis. Notably, metagenomic analyses of feces of the cranberry extract-treated mice&#xD;
      suggested that these metabolic effects were associated with a dramatic increase in the&#xD;
      proportion of Akkermansia muciniphila, a dominant commensal bacterium in the intestinal mucus&#xD;
      layer which has received particular attention in the last few years since its abundance is&#xD;
      associated with improved metabolic health and beneficial responses to various interventions&#xD;
      in both mice and humans with obesity and diabetes. Polyphenols are now recognized as potent&#xD;
      molecules capable to protect against obesity-linked metabolic diseases and dysbiosis. Among&#xD;
      polyphenols, there is increasing evidence supporting the beneficial impact of dietary&#xD;
      proanthocyanidins. Cranberries being rich in proanthocyanidins, we believe that these&#xD;
      phyto-elements could be associated to their beneficial effects. On the other hand, apart from&#xD;
      the recognized beneficial effects of fibers on gut health, their association with high&#xD;
      molecular proanthocyanidins could also contribute to their health benefits.&#xD;
&#xD;
      The main objective of this study is to investigate in a cross-over randomized&#xD;
      placebo-controlled clinical trial the beneficial properties of a whole cranberry powder on&#xD;
      gut microbiota, intestinal health and metabolic syndrome parameters in overweight men.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 15, 2018</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 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>Crossover 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 Gut Microbiota Diversity</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Global variation of the fecal microbiota</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Endotoxemia</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Intestinal permeability</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Plasma zonulin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Inflammation state of the tissue</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Fecal calprotectin and chromogranin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Short chain fatty acids in the feces</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Measure short chain fatty acids in the feces</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Gut health and stool consistency</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Evaluation of gastrointestinal symptoms and stool consistency using standardized questionnaires</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Lipid profile</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL and Apolipoprotein B from the beginning to the end of two dietary treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in chronic inflammation</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Glucose homeostasis</measure>
    <time_frame>At the beginning and the end of each treatment (4 weeks each)</time_frame>
    <description>Evaluation of plasma fasting glucose and insulin concentration</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Overweight</condition>
  <condition>Insulin Resistance</condition>
  <condition>Microbiota</condition>
  <condition>Endotoxemia</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Cranberry</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Whole Cranberry Powder Supplements</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Cranberry powder</intervention_name>
    <description>3 capsules /day of whole cranberry powder (500mg/each)</description>
    <arm_group_label>Cranberry</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>3 capsules/day of a placebo comparator</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  overweight&#xD;
&#xD;
          -  fasting insulin &gt; 42 pmol/L&#xD;
&#xD;
          -  non smoking&#xD;
&#xD;
          -  Stable weight in the past 3 months&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  chronic diseases&#xD;
&#xD;
          -  Taking drugs that could affect glucose or lipid metabolism&#xD;
&#xD;
          -  Taking anti-inflammatory, immunosuppressant or anticoagulant drugs&#xD;
&#xD;
          -  Inflammatory bowel disease&#xD;
&#xD;
          -  vegetarians, vegan or following any restrictive dietary pattern or if they are big&#xD;
             consumers of berries (&gt;1 portion/day)&#xD;
&#xD;
          -  taking pre- and probiotics&#xD;
&#xD;
          -  antibiotics in the past 3 months or change in their regular medication&#xD;
&#xD;
          -  Major surgery in the past 3 months&#xD;
&#xD;
          -  taste aversion for cranberries or cranberry allergy or allergies to other ingredients&#xD;
             used in the placebo&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>André Marette, Ph.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>Institute of nutrition and functional foods, Laval University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institut sur la nutrition et les aliments fonctionnels</name>
      <address>
        <city>Québec</city>
        <zip>G1V 0A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 21, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 27, 2018</study_first_posted>
  <last_update_submitted>March 26, 2020</last_update_submitted>
  <last_update_submitted_qc>March 26, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laval University</investigator_affiliation>
    <investigator_full_name>André Marette</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>Overweight</mesh_term>
    <mesh_term>Metabolic Syndrome</mesh_term>
    <mesh_term>Insulin Resistance</mesh_term>
    <mesh_term>Syndrome</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/NCT03754504
org study id: MICA 2018-146
nct id: NCT03754504
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
It is of major importance to refine prevention strategies in order to alleviate inflammation,
      insulin resistance and metabolic syndrome and it appear that improving gut health and
      microbiota represent a promising strategy. Cranberry-enriched diets may help prevent
      metabolic syndrome and its associated chronic diseases by a protective effect of gut health
      and microbiota. It is therefore highly relevant to test the hypothesis that a whole cranberry
      powder supplements (which include a mixture of polyphenols, free and fiber-associated
      proanthocyanidins, and fruits fibers) is associated with changes on the gut health and
      microbiota playing a major role in alleviating inflammation and obesity-associated metabolic
      disorders.
Over the past decade it has become clear that the gut microbiota is a key determinant of
      obesity and that its perturbations by nutritional insults play a significant role in the
      development of metabolic complications such as insulin resistance, type 2 diabetes,
      cardiovascular diseases and non-alcoholic fatty liver disease. Indeed, there is growing
      amounts of studies that have shown that dysbiosis of the intestinal microbiota promotes
      obesity-linked chronic inflammation, and is causally related to diet-induced type 2 diabetes.
      Our group recently published that a polyphenol-rich cranberry extract exert striking effect
      on the gut microbiota of high-fat and high-sucrose fed mice, which was associated with
      prevention of diet-induced weight gain, visceral obesity, insulin resistance and hepatic
      steatosis. Notably, metagenomic analyses of feces of the cranberry extract-treated mice
      suggested that these metabolic effects were associated with a dramatic increase in the
      proportion of Akkermansia muciniphila, a dominant commensal bacterium in the intestinal mucus
      layer which has received particular attention in the last few years since its abundance is
      associated with improved metabolic health and beneficial responses to various interventions
      in both mice and humans with obesity and diabetes. Polyphenols are now recognized as potent
      molecules capable to protect against obesity-linked metabolic diseases and dysbiosis. Among
      polyphenols, there is increasing evidence supporting the beneficial impact of dietary
      proanthocyanidins. Cranberries being rich in proanthocyanidins, we believe that these
      phyto-elements could be associated to their beneficial effects. On the other hand, apart from
      the recognized beneficial effects of fibers on gut health, their association with high
      molecular proanthocyanidins could also contribute to their health benefits.

      The main objective of this study is to investigate in a cross-over randomized
      placebo-controlled clinical trial the beneficial properties of a whole cranberry powder on
      gut microbiota, intestinal health and metabolic syndrome parameters in overweight men.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Gut Microbiota Diversity
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Global variation of the fecal microbiota
measure: Change in Endotoxemia
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Plasma Lipopolysaccharides (LPS) and Lipopolysaccharide Binding Protein (LBP)
measure: Change in Intestinal permeability
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Plasma zonulin
measure: Change in Inflammation state of the tissue
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Fecal calprotectin and chromogranin
measure: Change in Short chain fatty acids in the feces
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Measure short chain fatty acids in the feces
measure: Change in Gut health and stool consistency
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Evaluation of gastrointestinal symptoms and stool consistency using standardized questionnaires
measure: Change in Lipid profile
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Evaluation of plasma triglycerides (TG), Total cholesterol, LDL, HDL and Apolipoprotein B from the beginning to the end of two dietary treatment
measure: Change in chronic inflammation
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Evaluation of plasma high sensitive C-Reactive Protein (hs-CRP)
measure: Change in Glucose homeostasis
time frame: At the beginning and the end of each treatment (4 weeks each)
description: Evaluation of plasma fasting glucose and insulin concentration
arm group label: Cranberry
arm group type: Experimental
description: Whole Cranberry Powder Supplements
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Dietary Supplement
intervention name: Cranberry powder
description: 3 capsules /day of whole cranberry powder (500mg/each)
arm group label: Cranberry
intervention type: Dietary Supplement
intervention name: Placebo
description: 3 capsules/day of a placebo comparator
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: Accepts Healthy Volunteers
last name: André Marette, Ph.D
role: Principal Investigator
affiliation: Institute of nutrition and functional foods, Laval University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Laval University
investigator full name: André Marette
investigator title: Professor
mesh term: Endotoxemia
mesh term: Overweight
mesh term: Metabolic Syndrome
mesh term: Insulin Resistance
mesh term: Syndrome