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Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy (CLE-EoE)

Primary Purpose

Eosinophilic Esophagitis

Status
Recruiting
Phase
Phase 1
Locations
Belgium
Study Type
Interventional
Intervention
personalized exclusion diet based on CLE
empiric exclusion diet
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Eosinophilic Esophagitis focused on measuring confocal laser endomicroscopy, 6-food elimination diet, personalized exclusion diet

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Jan TackRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Sham Comparator

Sham Comparator

Arm Label

CLE positive patients real/sham

CLE positive patients sham/real

CLE negative patients

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Difference in response
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

Secondary Outcome Measures

Further histological outcomes
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
Further histological outcomes
Difference in peak eosinophil count (eosinophils/HPF) before and after the targeted elimination diet, compared with the sham diet
Symptomatic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
difference in symptoms using the DSQ (dysphagia symptom questionnaire), with a score from 0 (meaning no symptoms) to 10 (worse outcome).
endoscopic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Difference in endoscopic reference score (EREFS) ranging from E0R0E0F0S0 (no endoscopic abnormalities) to E2R2E2F2S2 (worse endoscopic features)
change in esophageal and duodenal permeability parameters 1
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
change in esophageal and duodenal permeability parameters 2
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.
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 1
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 2
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.

Full Information

First Posted
March 15, 2022
Last Updated
January 12, 2023
Sponsor
Universitaire Ziekenhuizen KU Leuven
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1. Study Identification

Unique Protocol Identification Number
NCT05695456
Brief Title
Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy
Acronym
CLE-EoE
Official Title
Targeted Elimination Diet in EoE Patients Following Identification of Trigger Nutrients Using Confocal Laser Endomicroscopy
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 16, 2022 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitaire Ziekenhuizen KU Leuven

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Using confocal laser endomicroscopy (CLE), gastrointestinal allergic reactions to certain foods in the duodenum will be evaluated on a cellular level. After that, a personalized exclusion diet will be followed based on the CLE results for 6 weeks, sham-controlled, in a cross-over fashion. Gastroscopy with esophageal biopsies will be repeated after each diet.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Eosinophilic Esophagitis
Keywords
confocal laser endomicroscopy, 6-food elimination diet, personalized exclusion diet

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Phase 1, Phase 2
Interventional Study Model
Crossover Assignment
Model Description
A double-blind cross-over dietary elimination study: Patients with a positive CLE reaction to one or two specific nutrients will then be randomized to a blinded exclusion diet for 6 weeks of those nutrients or to exclusion of another tested nutrient that yielded no change in CLE (=sham diet), in a cross-over fashion. Patients with no CLE reaction will undergo an empirical exclusion diet of gluten-containing grains for 6 weeks. To mirror the crossover character of the intervention, CLE negative patients will then undergo a milk exclusion diet for 6 weeks (order is interchangeable).
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Nor the participant, nor the primary or secondary investigators involved in the study will know to which nutrients the patient reacted as assessed by CLE, nor will they know what the order of the diet is (sham or real). An investigator who did not participate in the CLE will give dietary instructions.
Allocation
Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
CLE positive patients real/sham
Arm Type
Active Comparator
Arm Description
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.
Arm Title
CLE positive patients sham/real
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
CLE negative patients
Arm Type
Sham Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
personalized exclusion diet based on CLE
Intervention Description
personalized exclusion diet based on CLE
Intervention Type
Other
Intervention Name(s)
empiric exclusion diet
Intervention Description
exclusion diet with milk or gluten-containing grains
Primary Outcome Measure Information:
Title
Difference in response
Description
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
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Further histological outcomes
Description
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
Time Frame
2 years
Title
Further histological outcomes
Description
Difference in peak eosinophil count (eosinophils/HPF) before and after the targeted elimination diet, compared with the sham diet
Time Frame
2 years
Title
Symptomatic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Description
difference in symptoms using the DSQ (dysphagia symptom questionnaire), with a score from 0 (meaning no symptoms) to 10 (worse outcome).
Time Frame
2 years
Title
endoscopic changes in patients undergoing duodenal CLE-targeted elimination diet compared to the sham diet
Description
Difference in endoscopic reference score (EREFS) ranging from E0R0E0F0S0 (no endoscopic abnormalities) to E2R2E2F2S2 (worse endoscopic features)
Time Frame
2 years
Title
change in esophageal and duodenal permeability parameters 1
Description
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
Time Frame
2 years
Title
change in esophageal and duodenal permeability parameters 2
Description
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.
Time Frame
2 years
Title
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Description
Baseline and post-exposure duodenal mast cell and eosinophil counts on histology
Time Frame
2 years
Title
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 1
Description
using ussing chamber experiments, where human biopsies our mounted in between two chambers, and the transepithelial electrical resistance (TEER) is measured across the chambers
Time Frame
2 years
Title
Differences in duodenal permeability measures in CLE positive, CLE negative EoE patients and healthy controls before and after nutrient application 2
Description
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.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Jan Tack, MD PhD
Phone
+3216345514
Email
jan.tack@kuleuven.be
Facility Information:
Facility Name
Jan Tack
City
Leuven
State/Province
Vlaams Brabant
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jan Tack, MD PhD
Phone
+3216345514
Email
jan.tack@kuleuven.be
First Name & Middle Initial & Last Name & Degree
Karlien Raymenants, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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

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