Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy (CLE-EoE)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Eosinophilic esophagitis is an antigen driven esophagitis, that is characterized by symptoms of dysphagia often leading to food impaction, and that leads to strictures and esophageal motility disorders, with a significant impact on quality of life. Current treatment options include proton pump inhibitors (PPI's) and topical steroids, and also the empiric 6-food elimination diet (6FED). In this diet, the 6 most frequently implicated foods are excluded and reintroduced one by one (milk, gluten containing grains, egg, soy, nuts, fish & shellfish). However, this is a complicated and long process, including several endoscopies with esophageal biopsies.
Confocal laser endomicroscopy (CLE) is a technique that allows to detect gastrointestinal allergic reactions in the duodenum, and to visualize them on a molecular level in real-time. The CLE probe is passed through the working channel of a standard gastroscope, up against the duodenal mucosa. After intravenous injection of fluorescein as contrast medium, the duodenal epithelium is visualized on a cellular level, including food protein mediated extravasation of fluorescein into the lumen. The 6 foods of the 6FED are sprayed on the epithelium one by one, after which a reaction is awaited. Previous use of CLE has shown that more than half of Eosinophilic esophagitis (EoE) patients reacts to one or more foods during CLE.
In this double blind randomized cross-over study the effect a personalized elimination diet, based on the reaction during CLE, is compared to a sham diet, in patients with eosinophilic esophagitis, and insufficient response or intolerance to PPI's. Both diets will be followed for 6 weeks, after which gastroscopy with esophageal biopsies will be repeated. Patients that do not have a reaction to the 6 foods will act as controls, following a control diet with milk and gluten in a cross-over fashion.
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jan Tack, MD PhD
- Phone Number: +3216345514
- Email: jan.tack@kuleuven.be
Study Locations
-
-
Vlaams Brabant
-
Leuven, Vlaams Brabant, Belgium, 3000
- Recruiting
- Jan Tack
-
Contact:
- Jan Tack, MD PhD
- Phone Number: +3216345514
- Email: jan.tack@kuleuven.be
-
Sub-Investigator:
- Karlien Raymenants, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
- Patients have had a trial of high-dose PPI for at least 8 weeks, with either documented non-response or intolerance to the medication
- Patients aged between 18 and 70 years old
- Signed written informed consent
- Eosinophilic Esophagitis, with peak eosinophil count of >15 eos/HPF and symptoms of dysphagia at least 2 days per week
- Patients have had a trial of high-dose PPI for at least 8 weeks, with either documented non-response or intolerance to the medication
- Patients aged between 18 and 70 years old
- Signed written informed consent
Exclusion criteria:
- IgE-mediated food anaphylaxis for 1 of the trigger nutrients
- History of major gastrointestinal surgery complicating esophago-gastro-duodenoscopy
- Gastro-esophageal reflux disease (GERD) Los Angeles grade C or D
- Esophageal strictures, too narrow to pass with a normal gastroscope
- Endoscopic dilation in the esophagus in the 4 weeks prior to inclusion
- Celiac disease
- Recent use (within two weeks) of non-steroidal anti-inflammatory drugs (NSAIDs), systemic histamine-receptor antagonists, mast cell stabilizers, opioids.
- Proton pump inhibitors must be either stopped for at least 4 weeks, or continued on a stable dosage throughout the study period.
- Corticosteroids should be stopped for at least 4 weeks.
- Allergy to fluorescein, Xylocain or Propofol
- Pregnant or lactating women
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Active Comparator: CLE positive patients real/sham
In this arm, participants who reacted to one or two nutrients during CLE will follow a personalized exclusion diet consistent of the nutrient to which they reacted, after which they will follow a sham diet in a blinded cross-over fashion.
|
personalized exclusion diet based on CLE
|
|
Sham Comparator: CLE positive patients sham/real
In this arm, participants who reacted to one or two nutrients during CLE will follow a sham diet for 6 weeks, and than a personalized exclusion diet consistent of the nutrient to which they reacted, in a blinded cross-over fashion.
|
personalized exclusion diet based on CLE
|
|
Sham Comparator: CLE negative patients
In this arm, participants who did not react to one of the nutrients during CLE will follow a control diet consistent of milk exclusion for 6 weeks, after which they will follow a gluten exclusion diet for 6 weeks, or the other way around.
|
exclusion diet with milk or gluten-containing grains
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Difference in response
Time Frame: 2 years
|
Difference in response (defined as normalization of peak eosinophil count in esophageal mucosal biopsies <15 eosinophils/HPF) in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Further histological outcomes
Time Frame: 2 years
|
Difference in deep remission (defined as reduction of peak eosinophil count <6 eosinophils/HPF) before and after the targeted elimination diet respectively, compared with the sham diet
|
2 years
|
|
Further histological outcomes
Time Frame: 2 years
|
Difference in peak eosinophil count (eosinophils/HPF) before and after the targeted elimination diet, compared with the sham diet
|
2 years
|
|
Symptomatic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Time Frame: 2 years
|
difference in symptoms using the DSQ (dysphagia symptom questionnaire), with a score from 0 (meaning no symptoms) to 10 (worse outcome).
|
2 years
|
|
endoscopic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Time Frame: 2 years
|
Difference in endoscopic reference score (EREFS) ranging from E0R0E0F0S0 (no endoscopic abnormalities) to E2R2E2F2S2 (worse endoscopic features)
|
2 years
|
|
change in esophageal and duodenal permeability parameters 1
Time Frame: 2 years
|
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
|
2 years
|
|
change in esophageal and duodenal permeability parameters 2
Time Frame: 2 years
|
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial flux of a high molecular weight protein is measured by labeling the molecule with a fluorescent dye.
|
2 years
|
|
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Time Frame: 2 years
|
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
|
2 years
|
|
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 1
Time Frame: 2 years
|
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
|
2 years
|
|
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 2
Time Frame: 2 years
|
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial flux of a high molecular weight protein is measured by labeling the molecule with a fluorescent dye.
|
2 years
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- S66223
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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