<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/NCT03037918</url>
  </required_header>
  <id_info>
    <org_study_id>R16-P132</org_study_id>
    <nct_id>NCT03037918</nct_id>
  </id_info>
  <brief_title>Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans</brief_title>
  <official_title>Effect of Yakult Ingestion on Diet-induced Insulin Resistance in Humans. A Large-cohort, Mechanistic Follow-up Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Loughborough University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Yakult Honsha Co., LTD</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Loughborough 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>
      Participants will be randomly allocated to either Yakult ingestion or a control group. For&#xD;
      the first 20 days, subjects will consume their normal diet (keeping a detailed food diary&#xD;
      throughout). On days 21-28 they will switch to a high-fat/high-calorie diet.&#xD;
&#xD;
      The investigators hypothesise that consuming a high-fat, high-energy diet for 7 days will&#xD;
      alter the composition of the gut microbiota and induce metabolic endotoxaemia / systemic&#xD;
      inflammation as well as decreasing whole body insulin sensitivity (as we have shown&#xD;
      previously). In contrast, the investigators hypothesise that consuming Yakult for 21 days&#xD;
      before and 7 days throughout the high-fat diet will maintain a favourable gut microbiota and&#xD;
      prevent metabolic endotoxaemia / systemic inflammation and thus maintain insulin action /&#xD;
      insulin sensitivity.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 3, 2017</start_date>
  <completion_date type="Actual">August 31, 2018</completion_date>
  <primary_completion_date type="Actual">August 31, 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>Open label, control trial</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants will be given a unique identifier, which will not disclose the treatment group. All biological samples will be labelled with only the unique identifier.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Whole body insulin sensitivity index</measure>
    <time_frame>The change between pre- and post-high fat diet (assessed on days 21 and 28)</time_frame>
    <description>Assessed by oral glucose tolerance test.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Body Mass Index</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Calculated from height and weight.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting plasma glucose concentration</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Measured in fasting plasma sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting serum insulin concentration</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Measured in fasting serum sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting plasma triglyceride concentration</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Measured in fasting plasma sample.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Metabolic endotoxaemia</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Plasma markers of endotoxaemia</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Markers of systemic inflammation</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Selected plasma cytokines and chemokines</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incretin response to glucose ingestion</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>GLP-1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Microbiome analysis</measure>
    <time_frame>Day 0, Day 21 and Day 28</time_frame>
    <description>Faecal DNA analysis of the gut microbiota</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">56</enrollment>
  <condition>Insulin Sensitivity</condition>
  <condition>Insulin Resistance</condition>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive 2 x 65mL doses of Yakult light per day, for 28 days.&#xD;
Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Yakult light</intervention_name>
    <description>A fermented milk drink containing the probiotic Lactobacillus casei Shirota</description>
    <arm_group_label>Treatment Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females&#xD;
&#xD;
          -  Aged 18-30&#xD;
&#xD;
          -  Physically active (exercising at least 3 times per week for more than 30 min at a&#xD;
             time)&#xD;
&#xD;
          -  Non-smoker&#xD;
&#xD;
          -  Free from cardiovascular or metabolic disease&#xD;
&#xD;
          -  Weight stable for at least 6 months&#xD;
&#xD;
          -  Normal body mass index (BMI: 18.5-24.9 kg/m2)*&#xD;
&#xD;
          -  Compliant (i.e. understands and is willing, able and likely to comply with all study&#xD;
             requirements)&#xD;
&#xD;
               -  Note: If BMI is &gt;24.9, but body fat % (as measured by bioelectrical impedance&#xD;
                  analysis) is below 21% in males and 31% in females, then the subject may still be&#xD;
                  recruited at the PI's discretion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Using probiotic or prebiotic supplements within the previous 3 months&#xD;
&#xD;
          -  Vegetarians and vegans&#xD;
&#xD;
          -  Diagnosis of insulin resistance, pre-diabetes or full diabetes&#xD;
&#xD;
          -  Underweight (determined as BMI less than 18.5 kg/m2)&#xD;
&#xD;
          -  Overweight or obese (determined as BMI greater than 24.9 kg/m2)&#xD;
&#xD;
          -  Those on a calorie controlled diet or other dietary restrictions that would prevent&#xD;
             them from consuming the probiotic treatment and high fat/high calorie diet.&#xD;
&#xD;
          -  Those who are unwilling to restrict their intake of fermented dairy products.&#xD;
&#xD;
          -  Those with known or suspected food intolerances, allergies or hypersensitivity&#xD;
&#xD;
          -  Women who are known to be pregnant or who are intending to become pregnant over the&#xD;
             course of the study.&#xD;
&#xD;
          -  Participation in another clinical trial&#xD;
&#xD;
          -  Those who have donated blood within 3 months of the screening visit and participants&#xD;
             for whom participation in this study would result in having donated more than 1500 ml&#xD;
             of blood in the previous 12 months.&#xD;
&#xD;
          -  Participants who take any form of regular medication that is known to affect either&#xD;
             the gut microbiota and/or insulin sensitivity or who have taken any antibiotics in the&#xD;
             previous 3 months.&#xD;
&#xD;
          -  Participants who know they would not be available for all the lab visits during the&#xD;
             4-week study period.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>30 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Carl J Hulston</last_name>
    <role>Principal Investigator</role>
    <affiliation>Loughborough University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Loughborough University</name>
      <address>
        <city>Loughborough</city>
        <state>Leicestershire</state>
        <zip>LE11 3TU</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>October 30, 2018</last_update_submitted>
  <last_update_submitted_qc>October 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 31, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Loughborough University</investigator_affiliation>
    <investigator_full_name>Carl Hulston</investigator_full_name>
    <investigator_title>Lecturer in Sports Nutrition</investigator_title>
  </responsible_party>
  <keyword>Gut Microbiota</keyword>
  <keyword>High Fat Diets</keyword>
  <keyword>Probiotics</keyword>
  <keyword>Glycaemic Control</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    <mesh_term>Insulin Resistance</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/NCT03037918
org study id: R16-P132
nct id: NCT03037918
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
Participants will be randomly allocated to either Yakult ingestion or a control group. For
      the first 20 days, subjects will consume their normal diet (keeping a detailed food diary
      throughout). On days 21-28 they will switch to a high-fat/high-calorie diet.

      The investigators hypothesise that consuming a high-fat, high-energy diet for 7 days will
      alter the composition of the gut microbiota and induce metabolic endotoxaemia / systemic
      inflammation as well as decreasing whole body insulin sensitivity (as we have shown
      previously). In contrast, the investigators hypothesise that consuming Yakult for 21 days
      before and 7 days throughout the high-fat diet will maintain a favourable gut microbiota and
      prevent metabolic endotoxaemia / systemic inflammation and thus maintain insulin action /
      insulin sensitivity.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Open label, control trial
primary purpose: Basic Science
masking: None (Open Label)
masking description: Participants will be given a unique identifier, which will not disclose the treatment group. All biological samples will be labelled with only the unique identifier.
measure: Whole body insulin sensitivity index
time frame: The change between pre- and post-high fat diet (assessed on days 21 and 28)
description: Assessed by oral glucose tolerance test.
measure: Body Mass Index
time frame: Day 0, Day 21 and Day 28
description: Calculated from height and weight.
measure: Fasting plasma glucose concentration
time frame: Day 0, Day 21 and Day 28
description: Measured in fasting plasma sample.
measure: Fasting serum insulin concentration
time frame: Day 0, Day 21 and Day 28
description: Measured in fasting serum sample.
measure: Fasting plasma triglyceride concentration
time frame: Day 0, Day 21 and Day 28
description: Measured in fasting plasma sample.
measure: Metabolic endotoxaemia
time frame: Day 0, Day 21 and Day 28
description: Plasma markers of endotoxaemia
measure: Markers of systemic inflammation
time frame: Day 0, Day 21 and Day 28
description: Selected plasma cytokines and chemokines
measure: Incretin response to glucose ingestion
time frame: Day 0, Day 21 and Day 28
description: GLP-1
measure: Microbiome analysis
time frame: Day 0, Day 21 and Day 28
description: Faecal DNA analysis of the gut microbiota
arm group label: Treatment Group
arm group type: Experimental
description: Participants will receive 2 x 65mL doses of Yakult light per day, for 28 days.
Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.
arm group label: Control Group
arm group type: No Intervention
description: Participants will consume a high-fat (65% of kilocalories) high-calorie (150% of requirements) diet from day 21 to day 28.
intervention type: Dietary Supplement
intervention name: Yakult light
description: A fermented milk drink containing the probiotic Lactobacillus casei Shirota
arm group label: Treatment Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 30 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Carl J Hulston
role: Principal Investigator
affiliation: Loughborough University
facility: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: Loughborough University
investigator full name: Carl Hulston
investigator title: Lecturer in Sports Nutrition
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin Resistance