<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/NCT03004118</url>
  </required_header>
  <id_info>
    <org_study_id>UDC1</org_study_id>
    <nct_id>NCT03004118</nct_id>
  </id_info>
  <brief_title>Therapeutic Effect of Ursodeoxycholic Acid in Functional Dyspepsia</brief_title>
  <official_title>Therapeutic Effect of Ursodeoxycholic Acid on Duodenal Permeability and Meal Related Sensory Motor Function in Functional Dyspepsia Patients</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators aim to evaluate ursochol as a therapy in functional dyspepsia. The&#xD;
      objectives of the study are to evaluate the effect of ursochol on duodenal permeability and&#xD;
      dyspeptic symptoms and on duodenal low-grade inflammation, bile acid composition, bile acid&#xD;
      receptor expression, nutrient tolerance and intragastric pressure.&#xD;
&#xD;
      Cross-over, controlled, randomized, double blinded, placebo-controlled trial with a 4 week&#xD;
      intake of ursodeoxycholic acid (ursochol) versus a 4 week intake of placebo and a 4 week&#xD;
      washout period in between. Two study days are planned during week 4 and week 12. During the&#xD;
      14 weeks, the patients have to fill in a diary. And for 14 weeks in total, the patients have&#xD;
      to discontinue intake of proton pump inhibitors, drugs effecting gastric motility and NSAIDs&#xD;
      and replace their oral anticonception with non-oral anticonception. Every two weeks of the&#xD;
      study the investigator will call the participants to see how they are/if they have any&#xD;
      discomforts or side effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Functional dyspepsia patients will be recruited and screened for inclusion in the study. The&#xD;
      participants will be asked to not take proton pump inhibitors, drugs effecting gastric&#xD;
      motility and NSAIDs and oral anticonception for fourteen weeks. First, they will stop with&#xD;
      their daily drug intake of PPIs and NSAIDs for two weeks, then they will take placebo or UDC&#xD;
      for four weeks, two doses every day during lunch and dinner. Afterwards, there will be a&#xD;
      washout period of four weeks, and again four weeks of UDC or placebo intake. The patients&#xD;
      will receive a diary in which they describe their symptoms/discomforts every day for 14&#xD;
      weeks. All participants and the investigator will be blinded to the nature (UDC or placebo)&#xD;
      of the pills. The random order in which a certain patient gets his pills has been decided by&#xD;
      the pharmacy of UZ Leuven and is also unknown for the investigator (double blinded). During&#xD;
      week two, four, six, eight, ten and twelve we will have a phone conversation with the&#xD;
      patients to discuss their symptoms/discomforts.&#xD;
&#xD;
      During week four and week twelve, the patients will come to the hospital for one day after an&#xD;
      overnight fast. First, they are asked to fill in a bundle of questionnaires concerning&#xD;
      physical complaints, depression, anxiety (disturbances), pain/disease, body/interoceptive&#xD;
      awareness, trauma/abuse and personality and to give a fecal sample that they've collected the&#xD;
      day before. The fecal sample will be used to evaluate the gastrointestinal microbiota in FD&#xD;
      patients. Then, two blood samples, to evaluate liver function parameters and bile acid&#xD;
      synthesis, will be taken and an endoscopy will be performed. All endoscopies will be&#xD;
      performed by an experienced endoscopist (Jan Tack) and nine duodenal biopsies (2 biopsies at&#xD;
      a time) (Radial Jaw™3 with needle; outside diameter 2.2mm; Boston Scientific, 302 Parkway,&#xD;
      Global Park, Heredia, Costa Rica) will be obtained. To measure the in vitro transepithelial&#xD;
      resistance, 3 biopsies will be examined using an adapted mini-Ussing chambers system. After&#xD;
      equilibration, the mucosal side of the tissue will be exposed to 4kDa FITC-dextran as a&#xD;
      measure of paracellular permeability. A sample will be taken from the serosal side during 2h&#xD;
      at 30min interval. The concentration of fluoresceïn will then be measured using a&#xD;
      fluorescence plate reader. Also, two biopsies will be used for mRNA extraction and subsequent&#xD;
      cDNA synthesis. This cDNA will be used to measure the gene expression of bile acid receptors&#xD;
      by means of real-time RT-PCR. In addition, one biopsy will be prepared for&#xD;
      immunohistochemistry and two will be used for western blot to measure changes in&#xD;
      distribution/expression of the bile acid receptor proteins. One biopsy will be obtained to&#xD;
      study ultrastructural alterations by transmission electron microscopy.&#xD;
&#xD;
      After the endoscopy, an aspiration catheter will be positioned in the duodenum. The position&#xD;
      of the catheter will be briefly checked by fluoroscopy (typically 2-3 seconds, however never&#xD;
      more than 15 seconds). After positioning of the catheter, it is fixed to the subject's chin&#xD;
      and he/she is asked to take place in a chair for the remainder of the experiment. For one&#xD;
      hour, every 15 minutes duodenal fluids will be collected during fasted state. Next, a high&#xD;
      resolution manometry catheter (HRM) will be placed in the gastric fundus to measure&#xD;
      intragastric pressure and a perfusion tube (OD 2 mm) will be introduced through the nose and&#xD;
      positioned in the stomach. After positioning of the catheters, they are fixed to the&#xD;
      subject's chin and he/she is asked to take place in a chair for the remainder of the&#xD;
      experiment. After a stabilization period of 15 minutes, intragastric infusion of the nutrient&#xD;
      drink (Nutridrink, Nutricia; 630 KJ, 6 g proteins, 18.4 g carbohydrates, and 5.8 g lipids per&#xD;
      100 mL) will start at a constant speed of 60 mL per minute (determined by an automated system&#xD;
      using a peristaltic pump). Intragastric pressure will be measured with a 36-channel high&#xD;
      resolution manometry system, through the intragastric manometry probe. At 1-minute intervals,&#xD;
      the subjects will be asked to score their satiation using a graphic rating scale that&#xD;
      combines verbal descriptors on a scale graded 0-5. At 5-minute intervals the volunteers will&#xD;
      be asked to fill out a VAS for 11 dyspeptic symptoms. The intragastric infusion will be&#xD;
      stopped as soon as the volunteers score maximally on one of the 11 epigastric symptoms or&#xD;
      when a score of 5 is reached on their satiety scores. 10 minutes thereafter, the catheters&#xD;
      will be disconnected and removed. After the nutrient drink infusion, duodenal fluids will be&#xD;
      collected every 15 minutes for 1.5 hour during fed state. Finally, the last catheter is&#xD;
      removed and the volunteer can go home.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date>January 2017</start_date>
  <completion_date type="Anticipated">November 2017</completion_date>
  <primary_completion_date type="Anticipated">November 2017</primary_completion_date>
  <phase>Phase 4</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Duodenal mucosal transepithelial electrical resistance (TEER) (Ohm*cm^2) measured with adapted ussing chamber system</measure>
    <time_frame>2 hours</time_frame>
    <description>Transepithelial resistance is a measure for mucosal integrity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duodenal mucosal paracellular passage of Fitc Dextran 4kDa (pmol) measured with FLUOstar Omega microplate reader.</measure>
    <time_frame>2 hours</time_frame>
    <description>Paracellular permeability is a measure for mucosal integrity</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dyspeptic symptom occurence and intensity during meal intake via questionnaire every 1 minute until end of the meal</measure>
    <time_frame>About 10 minutes</time_frame>
    <description>Scoring of dyspeptic symptom occurence by patients during nutrientdrink perfusion</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Daily occurence and intensity of dyspeptic symptoms via LPDS diary</measure>
    <time_frame>14 weeks</time_frame>
    <description>Leuven Postprandial Distress Scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Glycocholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Taurocholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycochenodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Taurochenodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Taurodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glycoursodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tauroursodeoxycholic acid concentration (mM)</measure>
    <time_frame>14 weeks</time_frame>
    <description>Bile salt</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein expression of duodenal bile acid receptor VDR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein expression of duodenal bile acid receptor FXR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein expression of duodenal bile acid receptor PXR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein expression of duodenal bile acid receptor TGR5</measure>
    <time_frame>14 weeks</time_frame>
    <description>Western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Protein expression of duodenal bile acid receptor CAR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Western blot</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RNA expression of duodenal bile acid receptor VDR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Real time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RNA expression of duodenal bile acid receptor FXR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Real time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RNA expression of duodenal bile acid receptor PXR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Real time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RNA expression of duodenal bile acid receptor TGR5</measure>
    <time_frame>14 weeks</time_frame>
    <description>Real time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RNA expression of duodenal bile acid receptor CAR</measure>
    <time_frame>14 weeks</time_frame>
    <description>Real time RT-PCR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Intragastric pressure measurement via an high resolution manometry (HRM) probe</measure>
    <time_frame>1 hour</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mast cell count in duodenal biopsies (number of mastcells/ mm^2 lamina propria)</measure>
    <time_frame>14 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Eosinophil count in duodenal biopsies (number of eosinophils/ mm^2 lamina propria)</measure>
    <time_frame>14 weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">16</enrollment>
  <condition>Functional Dyspepsia</condition>
  <arm_group>
    <arm_group_label>Ursochol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>About 10.5mg/kg/day of ursochol (calculated before start study for each participant individually) (combination of ursochol 150 and 300) divided in 2 doses per day (during lunch and dinner). Oral intake. Tablets. 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Same amount of pills as ursochol (calculated before start study for each participant individually) divided in 2 doses per day (during lunch and dinner). Oral intake. Tablets. 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Nutridrink</intervention_name>
    <description>Liquid meal of 200ml</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>High resolution manometry probe</intervention_name>
    <description>Catheter inserted via the nose into the stomach to measure intragastric pressure.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>perfusion catheter</intervention_name>
    <description>Catheter inserted via the nose into the stomach to perfuse the nutridrink intragastricly.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>4 week oral intake (daily)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ursochol oral tablet</intervention_name>
    <description>4 week oral intake (daily) (dose of 10.5mg/kg/day)</description>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Duodenal fluid aspiration catheter</intervention_name>
    <description>Catheter inserted via the nose into the duodenum to aspirate duodenal fluids for 2.5 hours.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Duodenogastroscopy</intervention_name>
    <description>Catheter inserted via the mounth into the duodenum to take duodenal biopsies.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood sample</intervention_name>
    <description>Blood sample will be taken to measure liver enzyme serum levels and marker for bile acid synthesis.</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Ursochol</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Men and women (age 18-60 years) who meet the Rome IV criteria for functional dyspepsia can&#xD;
        participate in the study. For 14 weeks, patients need to discontinue their intake of proton&#xD;
        pump inhibitors, drugs effecting gastric motility and NSAIDs. If a female participant takes&#xD;
        oral anticonception, she has to switch to non-oral anticonception for this study. All&#xD;
        participants will receive and sign a copy of the informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  refused informed consent&#xD;
&#xD;
          -  pregnant women or women who are breastfeeding&#xD;
&#xD;
          -  diabetes mellitus&#xD;
&#xD;
          -  celiac disease&#xD;
&#xD;
          -  coagulation disorders/anticoagulant therapy&#xD;
&#xD;
          -  not well functioning liver and gallbladder&#xD;
&#xD;
          -  active stomach or gut ulcer&#xD;
&#xD;
          -  biliary colic, calcified gallstones&#xD;
&#xD;
          -  acute infection of gallbladder or bile ducts, bile duct obstruction&#xD;
&#xD;
          -  intestinal disorders such as ulcerative colitis, Crohn's disease&#xD;
&#xD;
          -  lactose intolerance&#xD;
&#xD;
          -  allergies/sensitivity (asthma, allergic to bile acids, eczema, allergic&#xD;
             rhinoconjunctivitis)&#xD;
&#xD;
          -  Intake of oral anticonception, barbiturates, antacid, colestyramine or colestipol,&#xD;
             nitrendipine, cyclosporine, ciprofloxacine, rosuvastatine.&#xD;
&#xD;
          -  first degree relatives with celiac disease, Crohn's disease or type I diabetes&#xD;
             mellitus Severe kidney malfunction&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Jan Tack, prof dr</last_name>
    <phone>+3216 37 74 74</phone>
    <email>jan.tack@med.kuleuven.be</email>
  </overall_contact>
  <verification_date>November 2016</verification_date>
  <study_first_submitted>December 5, 2016</study_first_submitted>
  <study_first_submitted_qc>December 21, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 28, 2016</study_first_posted>
  <last_update_submitted>December 21, 2016</last_update_submitted>
  <last_update_submitted_qc>December 21, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">December 28, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyspepsia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ursodeoxycholic Acid</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03004118
org study id: UDC1
nct id: NCT03004118
lead sponsor: 
has dmc: No
The investigators aim to evaluate ursochol as a therapy in functional dyspepsia. The
      objectives of the study are to evaluate the effect of ursochol on duodenal permeability and
      dyspeptic symptoms and on duodenal low-grade inflammation, bile acid composition, bile acid
      receptor expression, nutrient tolerance and intragastric pressure.

      Cross-over, controlled, randomized, double blinded, placebo-controlled trial with a 4 week
      intake of ursodeoxycholic acid (ursochol) versus a 4 week intake of placebo and a 4 week
      washout period in between. Two study days are planned during week 4 and week 12. During the
      14 weeks, the patients have to fill in a diary. And for 14 weeks in total, the patients have
      to discontinue intake of proton pump inhibitors, drugs effecting gastric motility and NSAIDs
      and replace their oral anticonception with non-oral anticonception. Every two weeks of the
      study the investigator will call the participants to see how they are/if they have any
      discomforts or side effects.
Functional dyspepsia patients will be recruited and screened for inclusion in the study. The
      participants will be asked to not take proton pump inhibitors, drugs effecting gastric
      motility and NSAIDs and oral anticonception for fourteen weeks. First, they will stop with
      their daily drug intake of PPIs and NSAIDs for two weeks, then they will take placebo or UDC
      for four weeks, two doses every day during lunch and dinner. Afterwards, there will be a
      washout period of four weeks, and again four weeks of UDC or placebo intake. The patients
      will receive a diary in which they describe their symptoms/discomforts every day for 14
      weeks. All participants and the investigator will be blinded to the nature (UDC or placebo)
      of the pills. The random order in which a certain patient gets his pills has been decided by
      the pharmacy of UZ Leuven and is also unknown for the investigator (double blinded). During
      week two, four, six, eight, ten and twelve we will have a phone conversation with the
      patients to discuss their symptoms/discomforts.

      During week four and week twelve, the patients will come to the hospital for one day after an
      overnight fast. First, they are asked to fill in a bundle of questionnaires concerning
      physical complaints, depression, anxiety (disturbances), pain/disease, body/interoceptive
      awareness, trauma/abuse and personality and to give a fecal sample that they've collected the
      day before. The fecal sample will be used to evaluate the gastrointestinal microbiota in FD
      patients. Then, two blood samples, to evaluate liver function parameters and bile acid
      synthesis, will be taken and an endoscopy will be performed. All endoscopies will be
      performed by an experienced endoscopist (Jan Tack) and nine duodenal biopsies (2 biopsies at
      a time) (Radial Jaw™3 with needle; outside diameter 2.2mm; Boston Scientific, 302 Parkway,
      Global Park, Heredia, Costa Rica) will be obtained. To measure the in vitro transepithelial
      resistance, 3 biopsies will be examined using an adapted mini-Ussing chambers system. After
      equilibration, the mucosal side of the tissue will be exposed to 4kDa FITC-dextran as a
      measure of paracellular permeability. A sample will be taken from the serosal side during 2h
      at 30min interval. The concentration of fluoresceïn will then be measured using a
      fluorescence plate reader. Also, two biopsies will be used for mRNA extraction and subsequent
      cDNA synthesis. This cDNA will be used to measure the gene expression of bile acid receptors
      by means of real-time RT-PCR. In addition, one biopsy will be prepared for
      immunohistochemistry and two will be used for western blot to measure changes in
      distribution/expression of the bile acid receptor proteins. One biopsy will be obtained to
      study ultrastructural alterations by transmission electron microscopy.

      After the endoscopy, an aspiration catheter will be positioned in the duodenum. The position
      of the catheter will be briefly checked by fluoroscopy (typically 2-3 seconds, however never
      more than 15 seconds). After positioning of the catheter, it is fixed to the subject's chin
      and he/she is asked to take place in a chair for the remainder of the experiment. For one
      hour, every 15 minutes duodenal fluids will be collected during fasted state. Next, a high
      resolution manometry catheter (HRM) will be placed in the gastric fundus to measure
      intragastric pressure and a perfusion tube (OD 2 mm) will be introduced through the nose and
      positioned in the stomach. After positioning of the catheters, they are fixed to the
      subject's chin and he/she is asked to take place in a chair for the remainder of the
      experiment. After a stabilization period of 15 minutes, intragastric infusion of the nutrient
      drink (Nutridrink, Nutricia; 630 KJ, 6 g proteins, 18.4 g carbohydrates, and 5.8 g lipids per
      100 mL) will start at a constant speed of 60 mL per minute (determined by an automated system
      using a peristaltic pump). Intragastric pressure will be measured with a 36-channel high
      resolution manometry system, through the intragastric manometry probe. At 1-minute intervals,
      the subjects will be asked to score their satiation using a graphic rating scale that
      combines verbal descriptors on a scale graded 0-5. At 5-minute intervals the volunteers will
      be asked to fill out a VAS for 11 dyspeptic symptoms. The intragastric infusion will be
      stopped as soon as the volunteers score maximally on one of the 11 epigastric symptoms or
      when a score of 5 is reached on their satiety scores. 10 minutes thereafter, the catheters
      will be disconnected and removed. After the nutrient drink infusion, duodenal fluids will be
      collected every 15 minutes for 1.5 hour during fed state. Finally, the last catheter is
      removed and the volunteer can go home.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Duodenal mucosal transepithelial electrical resistance (TEER) (Ohm*cm^2) measured with adapted ussing chamber system
time frame: 2 hours
description: Transepithelial resistance is a measure for mucosal integrity
measure: Duodenal mucosal paracellular passage of Fitc Dextran 4kDa (pmol) measured with FLUOstar Omega microplate reader.
time frame: 2 hours
description: Paracellular permeability is a measure for mucosal integrity
measure: Dyspeptic symptom occurence and intensity during meal intake via questionnaire every 1 minute until end of the meal
time frame: About 10 minutes
description: Scoring of dyspeptic symptom occurence by patients during nutrientdrink perfusion
measure: Daily occurence and intensity of dyspeptic symptoms via LPDS diary
time frame: 14 weeks
description: Leuven Postprandial Distress Scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome.
measure: Glycocholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Taurocholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Glycochenodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Taurochenodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Glycodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Taurodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Glycoursodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Tauroursodeoxycholic acid concentration (mM)
time frame: 14 weeks
description: Bile salt
measure: Protein expression of duodenal bile acid receptor VDR
time frame: 14 weeks
description: Western blot
measure: Protein expression of duodenal bile acid receptor FXR
time frame: 14 weeks
description: Western blot
measure: Protein expression of duodenal bile acid receptor PXR
time frame: 14 weeks
description: Western blot
measure: Protein expression of duodenal bile acid receptor TGR5
time frame: 14 weeks
description: Western blot
measure: Protein expression of duodenal bile acid receptor CAR
time frame: 14 weeks
description: Western blot
measure: RNA expression of duodenal bile acid receptor VDR
time frame: 14 weeks
description: Real time RT-PCR
measure: RNA expression of duodenal bile acid receptor FXR
time frame: 14 weeks
description: Real time RT-PCR
measure: RNA expression of duodenal bile acid receptor PXR
time frame: 14 weeks
description: Real time RT-PCR
measure: RNA expression of duodenal bile acid receptor TGR5
time frame: 14 weeks
description: Real time RT-PCR
measure: RNA expression of duodenal bile acid receptor CAR
time frame: 14 weeks
description: Real time RT-PCR
measure: Intragastric pressure measurement via an high resolution manometry (HRM) probe
time frame: 1 hour
measure: Mast cell count in duodenal biopsies (number of mastcells/ mm^2 lamina propria)
time frame: 14 weeks
measure: Eosinophil count in duodenal biopsies (number of eosinophils/ mm^2 lamina propria)
time frame: 14 weeks
arm group label: Ursochol
arm group type: Active Comparator
description: About 10.5mg/kg/day of ursochol (calculated before start study for each participant individually) (combination of ursochol 150 and 300) divided in 2 doses per day (during lunch and dinner). Oral intake. Tablets. 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Same amount of pills as ursochol (calculated before start study for each participant individually) divided in 2 doses per day (during lunch and dinner). Oral intake. Tablets. 4 weeks.
intervention type: Dietary Supplement
intervention name: Nutridrink
description: Liquid meal of 200ml
arm group label: Placebo
arm group label: Ursochol
intervention type: Device
intervention name: High resolution manometry probe
description: Catheter inserted via the nose into the stomach to measure intragastric pressure.
arm group label: Placebo
arm group label: Ursochol
intervention type: Device
intervention name: perfusion catheter
description: Catheter inserted via the nose into the stomach to perfuse the nutridrink intragastricly.
arm group label: Placebo
arm group label: Ursochol
intervention type: Drug
intervention name: Placebo Oral Tablet
description: 4 week oral intake (daily)
arm group label: Placebo
intervention type: Drug
intervention name: Ursochol oral tablet
description: 4 week oral intake (daily) (dose of 10.5mg/kg/day)
arm group label: Ursochol
intervention type: Device
intervention name: Duodenal fluid aspiration catheter
description: Catheter inserted via the nose into the duodenum to aspirate duodenal fluids for 2.5 hours.
arm group label: Placebo
arm group label: Ursochol
intervention type: Procedure
intervention name: Duodenogastroscopy
description: Catheter inserted via the mounth into the duodenum to take duodenal biopsies.
arm group label: Placebo
arm group label: Ursochol
intervention type: Procedure
intervention name: Blood sample
description: Blood sample will be taken to measure liver enzyme serum levels and marker for bile acid synthesis.
arm group label: Placebo
arm group label: Ursochol
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jan Tack, prof dr
phone: +3216 37 74 74
email: jan.tack@med.kuleuven.be
responsible party type: Sponsor
mesh term: Dyspepsia
mesh term: Ursodeoxycholic Acid
sharing ipd: No