Confocal Laser Endomicroscopy Based Diet in Functional Dyspepsia

Study Overview
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Brief Summary
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After a thorough baseline evaluation, functional dyspepsia (FD) patients will be exposed to nutrients while undergoing confocal laser endomicroscopy (CLE). Patients presenting an acute mucosal reaction upon nutrient exposure will be instructed to exclude their respective trigger nutrient or a nutrient without mucosal reaction (=sham diet) from their diet for 4 weeks in a randomized, blinded crossover fashion. The aim of the trial is to assess the symptomatic response to the targeted diet and further elucidate mechanisms underlying the acute mucosal reactions observed in CLE upon nutrient exposure.

Official Title
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Targeted Elimination Diet in FD Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy

Conditions
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Functional Dyspepsia

Intervention / Treatment
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* Other: Real diet
* Other: Sham diet
* Other: Wheat exclusion diet
* Other: Soy exclusion diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-70 y/o (70 years included) Male or female subjects FD (PDS, EPS or overlap) according to Rome IV criteria Provide written informed consent to participate in the study Women of child-bearing potential agree to apply a highly effective method of birth control during the entire duration of the trial. Highly effective birth control is defined as those which result in a low failure rate (i.e., less than 1% per year) when used constantly and correctly such as implants, injectables, combined oral contraceptive method, or some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. Women of non-childbearing potential may be included if surgically sterile (tubal ligation or hysterectomy) or postmenopausal with at least 2 year without spontaneous menses. Subjects who are capable to understand the study and the questionnaires, and to comply with the study requirements. Exclusion Criteria: Pregnant or breastfeeding women History of major surgery of the gastrointestinal tract (cholecystectomy and uncomplicated appendectomy are allowed) Symptoms predominantly associated with irritable bowel syndrome or gastro-esophageal reflux disease IgE-mediated food allergies identified by immunocaps blood tests Known underlying organic gastrointestinal disease Current use of NSAIDs, proton-pump inhibitors, systemic histamine-receptor antagonists, mast cell stabilizers, corticosteroids, opioids (need to be stopped at least 2 weeks). Use of antibiotics in the past 6 weeks. Allergy to Fluorescein or Propofol Known celiac disease Following a diet, interfering with the study diet in opinion to the investigators

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Real diet<br>Diet excluding the trigger nutrient identified by an acute mucosal reaction in CLE | Other: Real diet<br>* Diet excluding either trigger nutrient in a blinded crossover fashion (CLE positive individuals with identified trigger)<br>|
| Sham Comparator: Sham diet<br>Diet excluding a sham nutrient without acute mucosal reaction in CLE | Other: Sham diet<br>* Diet excluding either sham nutrient in a blinded crossover fashion (CLE positive individuals with identified trigger) or wheat and soy in a blinded crossover fashion (CLE negative individuals without identified trigger)<br>|
| Active Comparator: Wheat exclusion diet<br>In patients without identified trigger nutrient (i.e. no acute mucosal reaction to any nutrient), wheat will be excluded as an empirical diet in crossover fashion with soy. | Other: Wheat exclusion diet<br>* Diet excluding wheat in a blinded crossover fashion (CLE negative individuals without identified trigger)<br>|
| Active Comparator: Soy exclusion diet<br>In patients without identified trigger nutrient (i.e. no acute mucosal reaction to any nutrient), wheat will be excluded as an empirical diet in crossover fashion with soy. | Other: Soy exclusion diet<br>* Diet excluding soy in a blinded crossover fashion (CLE negative individuals without identified trigger)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder rates in targeted diet vs sham diet | Response defined by an improvement of minimum 0.5 points on the LPDS scale | After 4 weeks of dietary intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline duodenal transepithelial electrical resistance between groups | Differences in baseline permeability measures (TEER and flux, measured with ussing chambers on duodenal biopsies) between CLE positive and negative patients and healthy volunteers using Ussing chambers | At baseline | 
| Baseline duodenal flux of horse-radish peroxidase between groups | Differences in baseline permeability measures (flux, measured with ussing chambers on duodenal biopsies) between CLE positive and negative patients and healthy volunteers using Ussing chambers | At baseline | 
| Evolution of duodenal flux of horse-radish peroxidase between dietary interventions | Differences in permeability measures (HRP flux, measured with ussing chambers on duodenal biopsies) between dietary interventions (i.e. verum, sham, wheat and soy) during the dietary interventions using urinary Lactulose/Mannitol/Sucralose ratio | Baseline and after 4 weeks of diet | 
| Evolution of duodenal transepithelial electrical resistance between dietary interventions | Differences in permeability measures (TEER, measured with ussing chambers on duodenal biopsies) between dietary interventions (i.e. verum, sham, wheat and soy) during the dietary interventions using urinary Lactulose/Mannitol/Sucralose ratio | Baseline and after 4 weeks of diet | 
| Baseline mucosal immune cell composition between groups | Differences in baseline mucosal mast-cell and eosinophil counts between CLE positive and negative patients | Baseline |