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Therapeutic Effect of Ursodeoxycholic Acid in Functional Dyspepsia

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ClinicalTrials.gov Identifier: NCT03004118
Recruitment Status : Not yet recruiting
First Posted : December 28, 2016
Last Update Posted : December 28, 2016
Sponsor:
Information provided by (Responsible Party):
Universitaire Ziekenhuizen Leuven

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Functional Dyspepsia Dietary Supplement: Nutridrink Device: High resolution manometry probe Device: perfusion catheter Drug: Placebo Oral Tablet Drug: Ursochol oral tablet Device: Duodenal fluid aspiration catheter Procedure: Duodenogastroscopy Procedure: Blood sample Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Therapeutic Effect of Ursodeoxycholic Acid on Duodenal Permeability and Meal Related Sensory Motor Function in Functional Dyspepsia Patients
Study Start Date : January 2017
Estimated Primary Completion Date : November 2017
Estimated Study Completion Date : November 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Indigestion
Drug Information available for: Ursodiol

Arm Intervention/treatment
Active Comparator: Ursochol
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.
Dietary Supplement: Nutridrink
Liquid meal of 200ml

Device: High resolution manometry probe
Catheter inserted via the nose into the stomach to measure intragastric pressure.

Device: perfusion catheter
Catheter inserted via the nose into the stomach to perfuse the nutridrink intragastricly.

Drug: Ursochol oral tablet
4 week oral intake (daily) (dose of 10.5mg/kg/day)

Device: Duodenal fluid aspiration catheter
Catheter inserted via the nose into the duodenum to aspirate duodenal fluids for 2.5 hours.

Procedure: Duodenogastroscopy
Catheter inserted via the mounth into the duodenum to take duodenal biopsies.

Procedure: Blood sample
Blood sample will be taken to measure liver enzyme serum levels and marker for bile acid synthesis.

Placebo Comparator: Placebo
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.
Dietary Supplement: Nutridrink
Liquid meal of 200ml

Device: High resolution manometry probe
Catheter inserted via the nose into the stomach to measure intragastric pressure.

Device: perfusion catheter
Catheter inserted via the nose into the stomach to perfuse the nutridrink intragastricly.

Drug: Placebo Oral Tablet
4 week oral intake (daily)

Device: Duodenal fluid aspiration catheter
Catheter inserted via the nose into the duodenum to aspirate duodenal fluids for 2.5 hours.

Procedure: Duodenogastroscopy
Catheter inserted via the mounth into the duodenum to take duodenal biopsies.

Procedure: Blood sample
Blood sample will be taken to measure liver enzyme serum levels and marker for bile acid synthesis.




Primary Outcome Measures :
  1. Duodenal mucosal transepithelial electrical resistance (TEER) (Ohm*cm^2) measured with adapted ussing chamber system [ Time Frame: 2 hours ]
    Transepithelial resistance is a measure for mucosal integrity

  2. Duodenal mucosal paracellular passage of Fitc Dextran 4kDa (pmol) measured with FLUOstar Omega microplate reader. [ Time Frame: 2 hours ]
    Paracellular permeability is a measure for mucosal integrity

  3. Dyspeptic symptom occurence and intensity during meal intake via questionnaire every 1 minute until end of the meal [ Time Frame: About 10 minutes ]
    Scoring of dyspeptic symptom occurence by patients during nutrientdrink perfusion

  4. Daily occurence and intensity of dyspeptic symptoms via LPDS diary [ Time Frame: 14 weeks ]
    Leuven Postprandial Distress Scale, a questionnaire for symptom assessment in the functional dyspepsia/postprandial distress syndrome.


Secondary Outcome Measures :
  1. Glycocholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  2. Taurocholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  3. Glycochenodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  4. Taurochenodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  5. Glycodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  6. Taurodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  7. Glycoursodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  8. Tauroursodeoxycholic acid concentration (mM) [ Time Frame: 14 weeks ]
    Bile salt

  9. Protein expression of duodenal bile acid receptor VDR [ Time Frame: 14 weeks ]
    Western blot

  10. Protein expression of duodenal bile acid receptor FXR [ Time Frame: 14 weeks ]
    Western blot

  11. Protein expression of duodenal bile acid receptor PXR [ Time Frame: 14 weeks ]
    Western blot

  12. Protein expression of duodenal bile acid receptor TGR5 [ Time Frame: 14 weeks ]
    Western blot

  13. Protein expression of duodenal bile acid receptor CAR [ Time Frame: 14 weeks ]
    Western blot

  14. RNA expression of duodenal bile acid receptor VDR [ Time Frame: 14 weeks ]
    Real time RT-PCR

  15. RNA expression of duodenal bile acid receptor FXR [ Time Frame: 14 weeks ]
    Real time RT-PCR

  16. RNA expression of duodenal bile acid receptor PXR [ Time Frame: 14 weeks ]
    Real time RT-PCR

  17. RNA expression of duodenal bile acid receptor TGR5 [ Time Frame: 14 weeks ]
    Real time RT-PCR

  18. RNA expression of duodenal bile acid receptor CAR [ Time Frame: 14 weeks ]
    Real time RT-PCR

  19. Intragastric pressure measurement via an high resolution manometry (HRM) probe [ Time Frame: 1 hour ]
  20. Mast cell count in duodenal biopsies (number of mastcells/ mm^2 lamina propria) [ Time Frame: 14 weeks ]
  21. Eosinophil count in duodenal biopsies (number of eosinophils/ mm^2 lamina propria) [ Time Frame: 14 weeks ]


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Men and women (age 18-60 years) who meet the Rome IV criteria for functional dyspepsia can participate in the study. For 14 weeks, patients need to discontinue their intake of proton pump inhibitors, drugs effecting gastric motility and NSAIDs. If a female participant takes oral anticonception, she has to switch to non-oral anticonception for this study. All participants will receive and sign a copy of the informed consent.

Exclusion Criteria:

  • refused informed consent
  • pregnant women or women who are breastfeeding
  • diabetes mellitus
  • celiac disease
  • coagulation disorders/anticoagulant therapy
  • not well functioning liver and gallbladder
  • active stomach or gut ulcer
  • biliary colic, calcified gallstones
  • acute infection of gallbladder or bile ducts, bile duct obstruction
  • intestinal disorders such as ulcerative colitis, Crohn's disease
  • lactose intolerance
  • allergies/sensitivity (asthma, allergic to bile acids, eczema, allergic rhinoconjunctivitis)
  • Intake of oral anticonception, barbiturates, antacid, colestyramine or colestipol, nitrendipine, cyclosporine, ciprofloxacine, rosuvastatine.
  • first degree relatives with celiac disease, Crohn's disease or type I diabetes mellitus Severe kidney malfunction

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03004118


Contacts
Contact: Jan Tack, prof dr +3216 37 74 74 jan.tack@med.kuleuven.be

Sponsors and Collaborators
Universitaire Ziekenhuizen Leuven

Responsible Party: Universitaire Ziekenhuizen Leuven
ClinicalTrials.gov Identifier: NCT03004118     History of Changes
Other Study ID Numbers: UDC1
First Posted: December 28, 2016    Key Record Dates
Last Update Posted: December 28, 2016
Last Verified: November 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Dyspepsia
Gastritis
Signs and Symptoms, Digestive
Signs and Symptoms
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Stomach Diseases
Ursodeoxycholic Acid
Cholagogues and Choleretics
Gastrointestinal Agents