<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/NCT03259685</url>
  </required_header>
  <id_info>
    <org_study_id>SBG 2017-136</org_study_id>
    <nct_id>NCT03259685</nct_id>
  </id_info>
  <brief_title>Effect of Non-nutritive Sweeteners of High Sugar Sweetened Beverages on Metabolic Health and Gut Microbiome</brief_title>
  <official_title>Effect of Free Sugar Replacement With Non-nutritive Sweeteners on Metabolic Health of High Sugar Sweetened Beverages Consumers: Potential Role of the Gut Microbiome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Laval University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Laval University</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>
      Increasing evidence suggest that artificial sweeteners such as saccharin, aspartame and&#xD;
      sucralose may not be as metabolically safe as they first appeared, and it has been proposed&#xD;
      that their consumption may be linked to important disturbances in the gut microbiome. Some in&#xD;
      vitro and in vivo studies suggest that the recently approved sugar substitute Stevia (eg.&#xD;
      steviol glycosides) can also influence intestinal homeostasis. However, it is not clear&#xD;
      whether this natural non-nutritive sweetener (NNS) could also cause metabolic and microbiome&#xD;
      disturbances as proposed for their synthetic counterparts. In fact, steviol glycosides may&#xD;
      even have a beneficial impact on glucose homeostasis and lipid metabolism possibly through a&#xD;
      positive action on intestinal health and gut microbiome, but this has yet to be&#xD;
      experimentally tested in a rigorous study.&#xD;
&#xD;
      The main objective of this project is to evaluate whether steviol glycosides sweetened&#xD;
      beverages (SGSB) or aspartame/acesulfame K sweetened beverages (AASB) exert beneficial,&#xD;
      neutral or detrimental effects on metabolic health of regular consumers of sugar-sweetened&#xD;
      beverages (SSBs), and whether modulation of the gut microbiome is involved in the resulting&#xD;
      impact of these NNSs on metabolic health.&#xD;
&#xD;
      As chronic overconsumption of SSBs is clearly associated with an increased cardiometabolic&#xD;
      risk, this study will be the first to determine the metabolic impact of replacing SSBs by&#xD;
      potentially &quot;healthier alternatives&quot; such as the increasingly popular stevia-based soft&#xD;
      drinks and aspartame-based soft drinks. The investigators will further investigate whether&#xD;
      these NNS can cause pernicious effects on intestinal health and the gut microbiome. It is a&#xD;
      crucial concern since the importance of this unsuspected key &quot;organ&quot; has been ignored for too&#xD;
      long and its important implication in many chronic societal diseases has just been&#xD;
      discovered.&#xD;
&#xD;
      Results of this study could have a direct influence on health, nutrition and even&#xD;
      agricultural policies as well as dietary guidelines around the world. This project is also&#xD;
      critically important as an increasing amount of health professionals such as physicians,&#xD;
      nurses and registered dietitians seek to provide evidenced-based guidance to individuals&#xD;
      looking for healthier alternatives to SSBs including stevia-based or aspartame-based soft&#xD;
      drinks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 18, 2017</start_date>
  <completion_date type="Anticipated">December 2025</completion_date>
  <primary_completion_date type="Actual">December 20, 2021</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>Changes in metabolic syndrome parameters including insulin/glucose homeostasis and lipid/lipoprotein metabolism in sugar-sweetened beverages (SSB) consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.</measure>
    <time_frame>18-24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in intestinal homeostasis of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.</measure>
    <time_frame>4-6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in gut microbiota composition of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.</measure>
    <time_frame>4-6 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in key molecular signaling pathways and metabolic regulatory networks identified through transcriptomics and metabolomics of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.</measure>
    <time_frame>6-12 months</time_frame>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">41</enrollment>
  <condition>Gut Microbiota</condition>
  <condition>Metabolic Syndrome</condition>
  <arm_group>
    <arm_group_label>Regular beverages</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Sugar sweetened soft drinks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Diet beverages</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Soft drinks sweetened with artificial non-nutritive sweeteners (i.e. aspartame, acesulfame-K)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Stevia beverages</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Soft drinks sweetened with natural non-nutritive sweeteners (i.e. steviol glycosides)</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>710 ml of regular soft drinks, taken daily for 10 weeks</intervention_name>
    <description>Subjects will consume regular soft drinks to test if there is a significant difference on the impact on gut microbiota composition and metabolic syndrome parameters between this treatment and the active treatments (diet and stevia beverages).</description>
    <arm_group_label>Regular beverages</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>710 ml of diet soft drinks, taken daily for 10 weeks</intervention_name>
    <description>Subjects will consume diet soft drinks during 10 weeks to test the possible effects of aspartame/acesulfame-K sweetened beverages on gut microbiota composition and on metabolic syndrome parameters.</description>
    <arm_group_label>Diet beverages</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>710 ml of stevia-sweetened soft drinks, taken daily for 10 weeks</intervention_name>
    <description>Subjects will consume soft drinks containing stevia during 10 weeks to test the possible effects of steviol glycosides sweetened beverages on gut microbiota composition and on metabolic syndrome parameters.</description>
    <arm_group_label>Stevia beverages</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women in good health&#xD;
&#xD;
          -  Soft drinks consumers (between 4 cans/week to 4 cans/day)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Metabolic disorders (hypertension, diabetes, hypercholesterolemia)&#xD;
&#xD;
          -  Daily consumption of more than 4 cans of soft drinks&#xD;
&#xD;
          -  Regular use of medication affecting study parameters&#xD;
&#xD;
          -  Change of medication (type or dose) in the last year&#xD;
&#xD;
          -  Use of antibiotics in the last 3 months&#xD;
&#xD;
          -  Change in natural health product use in the last 3 months&#xD;
&#xD;
          -  More than 2 alcohol drinks par day&#xD;
&#xD;
          -  Weight change of more than 5% in the last 3 months&#xD;
&#xD;
          -  Surgery in the last 3 months or planed during the study&#xD;
&#xD;
          -  Allergy or intolerance for products contained in soft drinks&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Marie-Claude Vohl</last_name>
    <role>Principal Investigator</role>
    <affiliation>Laval University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Laval University</name>
      <address>
        <city>Québec</city>
        <zip>G1V0A6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>August 21, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>September 6, 2022</last_update_submitted>
  <last_update_submitted_qc>September 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Laval University</investigator_affiliation>
    <investigator_full_name>Marie-Claude Vohl</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Non-nutritive sweeteners</keyword>
  <keyword>High Sugar Sweetened Beverages</keyword>
  <keyword>Diet</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metabolic 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/NCT03259685
org study id: SBG 2017-136
nct id: NCT03259685
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Increasing evidence suggest that artificial sweeteners such as saccharin, aspartame and
      sucralose may not be as metabolically safe as they first appeared, and it has been proposed
      that their consumption may be linked to important disturbances in the gut microbiome. Some in
      vitro and in vivo studies suggest that the recently approved sugar substitute Stevia (eg.
      steviol glycosides) can also influence intestinal homeostasis. However, it is not clear
      whether this natural non-nutritive sweetener (NNS) could also cause metabolic and microbiome
      disturbances as proposed for their synthetic counterparts. In fact, steviol glycosides may
      even have a beneficial impact on glucose homeostasis and lipid metabolism possibly through a
      positive action on intestinal health and gut microbiome, but this has yet to be
      experimentally tested in a rigorous study.

      The main objective of this project is to evaluate whether steviol glycosides sweetened
      beverages (SGSB) or aspartame/acesulfame K sweetened beverages (AASB) exert beneficial,
      neutral or detrimental effects on metabolic health of regular consumers of sugar-sweetened
      beverages (SSBs), and whether modulation of the gut microbiome is involved in the resulting
      impact of these NNSs on metabolic health.

      As chronic overconsumption of SSBs is clearly associated with an increased cardiometabolic
      risk, this study will be the first to determine the metabolic impact of replacing SSBs by
      potentially "healthier alternatives" such as the increasingly popular stevia-based soft
      drinks and aspartame-based soft drinks. The investigators will further investigate whether
      these NNS can cause pernicious effects on intestinal health and the gut microbiome. It is a
      crucial concern since the importance of this unsuspected key "organ" has been ignored for too
      long and its important implication in many chronic societal diseases has just been
      discovered.

      Results of this study could have a direct influence on health, nutrition and even
      agricultural policies as well as dietary guidelines around the world. This project is also
      critically important as an increasing amount of health professionals such as physicians,
      nurses and registered dietitians seek to provide evidenced-based guidance to individuals
      looking for healthier alternatives to SSBs including stevia-based or aspartame-based soft
      drinks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Changes in metabolic syndrome parameters including insulin/glucose homeostasis and lipid/lipoprotein metabolism in sugar-sweetened beverages (SSB) consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.
time frame: 18-24 months
measure: Changes in intestinal homeostasis of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.
time frame: 4-6 months
measure: Changes in gut microbiota composition of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.
time frame: 4-6 months
measure: Changes in key molecular signaling pathways and metabolic regulatory networks identified through transcriptomics and metabolomics of SSB consumers following regular, diet or stevia-sweetened beverages intakes for 10 weeks.
time frame: 6-12 months
arm group label: Regular beverages
arm group type: Active Comparator
description: Sugar sweetened soft drinks
arm group label: Diet beverages
arm group type: Experimental
description: Soft drinks sweetened with artificial non-nutritive sweeteners (i.e. aspartame, acesulfame-K)
arm group label: Stevia beverages
arm group type: Experimental
description: Soft drinks sweetened with natural non-nutritive sweeteners (i.e. steviol glycosides)
intervention type: Other
intervention name: 710 ml of regular soft drinks, taken daily for 10 weeks
description: Subjects will consume regular soft drinks to test if there is a significant difference on the impact on gut microbiota composition and metabolic syndrome parameters between this treatment and the active treatments (diet and stevia beverages).
arm group label: Regular beverages
intervention type: Other
intervention name: 710 ml of diet soft drinks, taken daily for 10 weeks
description: Subjects will consume diet soft drinks during 10 weeks to test the possible effects of aspartame/acesulfame-K sweetened beverages on gut microbiota composition and on metabolic syndrome parameters.
arm group label: Diet beverages
intervention type: Other
intervention name: 710 ml of stevia-sweetened soft drinks, taken daily for 10 weeks
description: Subjects will consume soft drinks containing stevia during 10 weeks to test the possible effects of steviol glycosides sweetened beverages on gut microbiota composition and on metabolic syndrome parameters.
arm group label: Stevia beverages
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Marie-Claude Vohl
role: Principal Investigator
affiliation: Laval University
facility: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: Laval University
investigator full name: Marie-Claude Vohl
investigator title: Professor
mesh term: Metabolic Syndrome