Confocal Laser Endomicroscopy Based Diet in Functional Dyspepsia (CLEFD)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Functional Dyspepsia
• Intervention / Treatment: Other: Real diet; Other: Sham diet; Other: Wheat exclusion diet; Other: Soy exclusion diet

• Study Type: Interventional
• Enrollment (Estimated): 65
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jolien Schol, MD; Phone Number: +3216345663; Email: jolien.schol@kuleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Jolien Schol, MD; Phone Number: +3216345663; Email: jolien.schol@kuleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Real diet; Diet excluding the trigger nutrient identified by an acute mucosal reaction in CLE	Other: Real diet; Diet excluding either trigger nutrient in a blinded crossover fashion (CLE positive individuals with identified trigger)
Sham Comparator: Sham diet; Diet excluding a sham nutrient without acute mucosal reaction in CLE	Other: Sham diet; 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)
Active Comparator: Wheat exclusion diet; 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; Diet excluding wheat in a blinded crossover fashion (CLE negative individuals without identified trigger)
Active Comparator: Soy exclusion diet; 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; Diet excluding soy in a blinded crossover fashion (CLE negative individuals without identified trigger)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2021
• Primary Completion (Estimated): July 31, 2025
• Study Completion (Estimated): August 31, 2025

Study Registration Dates

• First Submitted: December 9, 2021
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): July 3, 2024
• Last Update Submitted That Met QC Criteria: July 1, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Signs and Symptoms, Digestive; Dyspepsia
• Other Study ID Numbers: S65735

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No