<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/NCT03777787</url>
  </required_header>
  <id_info>
    <org_study_id>S61251</org_study_id>
    <nct_id>NCT03777787</nct_id>
  </id_info>
  <brief_title>Bitter Tastants and Reflux</brief_title>
  <official_title>The Relationship Between Acute Administration of a Bitter Compound and Transient Lower Esophageal Sphincter Relaxations and Reflux Events in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Universitaire Ziekenhuizen KU Leuven</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Universitaire Ziekenhuizen KU Leuven</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>
      Recently the relationship between intragastric pressure (IGP) and reflux events after a meal&#xD;
      was investigated, both in gastro-esophageal reflux disease (GERD) patients and in healthy&#xD;
      volunteers. Ingestion of a meal was accompanied by a drop in IGP. However, the magnitude of&#xD;
      this drop varied and was inversely correlated with the number of transient lower esophageal&#xD;
      sphincter relaxations (TLESRs) and the number of reflux events, both in patients and in&#xD;
      healthy volunteers: a smaller meal-induced drop in IGP was associated with a higher rate of&#xD;
      reflux events and vice versa. This finding suggests that a smaller meal-induced drop may act&#xD;
      as a trigger for reflux. It has been demonstrated that bitter administration leads to a&#xD;
      smaller meal-induced drop. Therefore, bitter can be a dietary trigger for TLESRs facilitating&#xD;
      the occurrence of symptoms of GERD. To evaluate this hypothesis, the researchers will study&#xD;
      the relationship between bitter and the occurrence of TLESRs and reflux events in healthy&#xD;
      volunteers. Additionally, it has been demonstrated that administering bitter also influences&#xD;
      the concentration of motilin. Therefore, the research team will also measure the&#xD;
      concentration of motilin to investigate whether changes in motilin concentrations can&#xD;
      influence the number of TLESRs, via a change in gastric tone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 14, 2019</start_date>
  <completion_date type="Actual">May 10, 2019</completion_date>
  <primary_completion_date type="Actual">May 10, 2019</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>
    <intervention_model_description>Randomized, double-blind, placebo-controlled study</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in number of TLESRs</measure>
    <time_frame>1 week</time_frame>
    <description>Changes in the number of transient lower esophageal sphincter relaxations (TLESRs) between the placebo and bitter condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in reflux</measure>
    <time_frame>1 week</time_frame>
    <description>The change in the number of reflux events between placebo and bitter condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in motility pattern</measure>
    <time_frame>1 week</time_frame>
    <description>The change in the intragastric pressure between placebo and bitter condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in motilin concentration</measure>
    <time_frame>1 week</time_frame>
    <description>The change in motilin concentration between placebo and bitter condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in symptoms</measure>
    <time_frame>1 week</time_frame>
    <description>Change in the number of volunteers reporting gastrointestinal symptoms between placebo and bitter condition</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Gastro Esophageal Reflux</condition>
  <arm_group>
    <arm_group_label>Bitter</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A single intragastric administration of denatonium benzoate (1 µmol/kg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>A single intragastric administration of placebo (water)</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Denatonium Benzoate</intervention_name>
    <description>A single intragastric administration of denatonium benzoate (1 µmol/kg)</description>
    <arm_group_label>Bitter</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Water</intervention_name>
    <description>A single intragastric administration of water</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy female volunteers&#xD;
&#xD;
          -  Age between 18 and 65&#xD;
&#xD;
          -  Written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A history of any upper GI symptoms or GI surgery;&#xD;
&#xD;
          -  Psychological disorders;&#xD;
&#xD;
          -  Concomitant use of other medication or treatments except for oral contraceptives;&#xD;
&#xD;
          -  Use of medication altering esophageal or GI motility;&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <zip>3000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>December 11, 2018</study_first_submitted>
  <study_first_submitted_qc>December 14, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 17, 2018</study_first_posted>
  <last_update_submitted>June 5, 2019</last_update_submitted>
  <last_update_submitted_qc>June 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Bitter</keyword>
  <keyword>TLESRs</keyword>
  <keyword>Gastric tone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gastroesophageal Reflux</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Denatonium</mesh_term>
  </intervention_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/NCT03777787
org study id: S61251
nct id: NCT03777787
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Recently the relationship between intragastric pressure (IGP) and reflux events after a meal
      was investigated, both in gastro-esophageal reflux disease (GERD) patients and in healthy
      volunteers. Ingestion of a meal was accompanied by a drop in IGP. However, the magnitude of
      this drop varied and was inversely correlated with the number of transient lower esophageal
      sphincter relaxations (TLESRs) and the number of reflux events, both in patients and in
      healthy volunteers: a smaller meal-induced drop in IGP was associated with a higher rate of
      reflux events and vice versa. This finding suggests that a smaller meal-induced drop may act
      as a trigger for reflux. It has been demonstrated that bitter administration leads to a
      smaller meal-induced drop. Therefore, bitter can be a dietary trigger for TLESRs facilitating
      the occurrence of symptoms of GERD. To evaluate this hypothesis, the researchers will study
      the relationship between bitter and the occurrence of TLESRs and reflux events in healthy
      volunteers. Additionally, it has been demonstrated that administering bitter also influences
      the concentration of motilin. Therefore, the research team will also measure the
      concentration of motilin to investigate whether changes in motilin concentrations can
      influence the number of TLESRs, via a change in gastric tone.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Randomized, double-blind, placebo-controlled study
primary purpose: Other
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in number of TLESRs
time frame: 1 week
description: Changes in the number of transient lower esophageal sphincter relaxations (TLESRs) between the placebo and bitter condition.
measure: Change in reflux
time frame: 1 week
description: The change in the number of reflux events between placebo and bitter condition.
measure: Change in motility pattern
time frame: 1 week
description: The change in the intragastric pressure between placebo and bitter condition.
measure: Change in motilin concentration
time frame: 1 week
description: The change in motilin concentration between placebo and bitter condition.
measure: Change in symptoms
time frame: 1 week
description: Change in the number of volunteers reporting gastrointestinal symptoms between placebo and bitter condition
arm group label: Bitter
arm group type: Experimental
description: A single intragastric administration of denatonium benzoate (1 µmol/kg)
arm group label: Placebo
arm group type: Placebo Comparator
description: A single intragastric administration of placebo (water)
intervention type: Dietary Supplement
intervention name: Denatonium Benzoate
description: A single intragastric administration of denatonium benzoate (1 µmol/kg)
arm group label: Bitter
intervention type: Dietary Supplement
intervention name: Water
description: A single intragastric administration of water
arm group label: Placebo
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Gastroesophageal Reflux
mesh term: Denatonium