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

Eosinophilic Esophagitis Clinical Trial

— CLE-EoE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05695456
• Other study ID #: S66223
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: February 16, 2022
• Est. completion date: December 2023

Study information

• Verified date: January 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Jan Tack, MD PhD
• Phone: +3216345514
• Email: jan.tack[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Eosinophilic Esophagitis
• Esophagitis

Intervention

Other:
• personalized exclusion diet based on CLE
personalized exclusion diet based on CLE
• empiric exclusion diet
exclusion diet with milk or gluten-containing grains

Locations

Country	Name	City	State
Belgium	Jan Tack	Leuven	Vlaams Brabant

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	2 years
Secondary	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	2 years
Secondary	Further histological outcomes	Difference in peak eosinophil count (eosinophils/HPF) before and after the targeted elimination diet, compared with the sham diet	2 years
Secondary	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).	2 years
Secondary	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)	2 years
Secondary	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	2 years
Secondary	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.	2 years
Secondary	Baseline and post-exposure duodenal mast cell and eosinophil counts on histology	Baseline and post-exposure duodenal mast cell and eosinophil counts on histology	2 years
Secondary	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	2 years
Secondary	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.	2 years