Pediatric Eosinophilic Esophagitis (pedEoE): Effect of Allergen Heat Denaturation on EoE Remission: a Pilot Trial

NCT ID: NCT06381219

Last Updated: 2024-04-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-12-19
• Study Completion Date: 2028-12-31

Brief Summary

The objective of the study is to study whether the introduction of heated food products (more specifically heated hen's egg and/or cow's milk) in children with EoE would be possible without re-occurrence of the eosinophilic inflammation, while the intake of less heated products might cause disease recidive. Moreover, we would like to study whether the gradual re-introduction of less heated products after the most heated form is tolerated, could lead to tolerance induction in EoE.

Detailed Description

If inclusion criteria are met, after obtaining informed consent from the parents (and when old enough, assent from the children) children with cow's milk and/or hen's egg induced pedEoE will be included in this pilot trial. Baseline blood will be obtained before in-house OFC procedure and serum will be stored for specific IgG4 analysis. In parallel, PBMCs will be isolated and stimulated in vitro with heat denatured proteins. B cells will be stained by 4-laserflow cytometry. IgG4 production in supernatants will be studied by ELISA (specific IgG4 by Immunocap 100). This procedure will be repeated during each gastroscopy.

Children will be provoked in-house, based on the written procedure available for heated egg or cow's milk provocation. Afterwards, they will introduce heated egg by cake or 20' boiled cow's milk at least three times a week for 8 weeks and will return to the hospital for a gastroscopy with biopsies. EoE remission will be studied on biopsies of the upper and lower esophagus by eosinophil staining within the routine anatomopathological laboratory within our hospital.

If remission remains, subjects will be invited to introduce less heated hen's egg or cow's milk for 8 weeks, after which they will return to the hospital for the second gastroscopy with similar procedure. This is repeated three times until 4' soft-boiled egg or 5' boiled cow's milk is introduced for 8 weeks. When remission remains after this introduction, the children and parents are offered the possibility to terminate the study or to introduce either raw egg (tiramisu or chocolate mousse) or uncooked UHT-treated cow's milk for 8 weeks after which gastroscopy with biopsies will be performed.

If remission is lost, they will return to the strict avoidance diet for at least 10 weeks after which they will return to the hospital for their second gastroscopy. Upon remission after avoidance, the children will remain eligible for another heat denatured food challenge (when on diet for both).

Conditions

Eosinophilic Esophagitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Cow's milk allergen heat denaturation

Children with an EoE in remission AND a previous diet excluding any form of cow's milk will undergo an oral food challenge with extensively heated cow's milk (20'). Afterwards they will be instructed to ensure regular intake of 20' heated cow's milk. After 8 weeks of (re)introduction they will be assessed for potential remaining remission (\<15 eosinophils/hpf on esophagal biopsies). If remission is sustained, they will sequentially decrease the degree of heat denaturation by decreasing the cooking time: 15', 10' and 5' cooked cow's milk. At the end, parents will have the choice to add a final step of raw cow's milk. After every 8 weeks of every new step, a gastroscopy will be performed to assess maintained remission. If remission is lost, they will go back to a strict avoidance diet for at least 10 weeks.

Group Type: OTHER

Implementation of cow's milk in decreasingly heated forms

Intervention Type: OTHER

Implementation of cow's milk in decreasingly heated forms to assess maintained remission of EoE

Hen's egg allergen heat denaturation

Children with an EoE in remission AND a previous diet excluding any form of hen's egg will undergo an oral food challenge with strongly heated hen's egg (in cake). Afterwards they will be instructed to ensure regular intake of cake. After 8 weeks of (re)introduction they will be assessed for potential remaining remission (\<15 eosinophils/hpf on esophagal biopsies). If remission is sustained, they will sequentially decrease the degree of heat denaturation as follows: hard-boiled egg, omelet and soft-boiled egg. At the end, parents will have the choice to add a final step of raw egg. After every 8 weeks of every new step, a gastroscopy will be performed to assess maintained remission. If remission is lost, they will go back to a strict avoidance diet for at least 10 weeks.

Group Type: OTHER

Implementation of hen's egg in decreasingly heated forms

Intervention Type: OTHER

Implementation of hen's egg in decreasingly heated forms to assess maintained remission of EoE

Interventions

Implementation of cow's milk in decreasingly heated forms

Implementation of cow's milk in decreasingly heated forms to assess maintained remission of EoE

Intervention Type: OTHER

Implementation of hen's egg in decreasingly heated forms

Implementation of hen's egg in decreasingly heated forms to assess maintained remission of EoE

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

All children (aged 12 months and older) presenting (since 1-1-2014: moment of diagnostic guideline standardization for pedEoE) with diagnosed pedEoE at UZ Leuven eliminating either hen's egg or cow's milk or both and in complete remission after their latest biopsy (no longer than 12 months earlier, but preferentially as short as possible after their latest biopsy) are eligible for the study. If the last biopsy has been performed more than 12 months earlier, a new gastro-duodenoscopy will be performed to verify remission and rule out e.g. active gastritis. If they are on PPI and/or local budesonide treatment, this should be stable for at least 3 months and will remain untouched during the entire study. We will include 18 pedEoE subjects suffering from cow's milk induced EoE and 18 suffering from hen's egg induced EoE.

Exclusion Criteria

• Children younger than 12 months
• Children with active pedEoE
• Children who refuse to adhere to the protocol
• Children with associated IgE mediated hen's egg and/or cow's milk allergy with specific IgE antibody titers that predict active (baked egg and/or baked milk) food allergy with cut-off titers as used at the consultation of allergy (KLL). Those children will become eligible however if their titers decrease while the study is still open.

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Dominque Bullens

Clinic Head in Pediatrics-Allergy at UZ Leuven, Head of the Allergy and Clinical Immunology Research group at KU Leuven (prof., dr.)

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ilse Hoffman, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Co-investigator, pediatric gastro-enterology

Gert De Hertogh, Prof. Dr.

Role: PRINCIPAL_INVESTIGATOR

Co-investigator, pathological anatomy

Locations

UZ Leuven Gasthuisberg

Leuven, Vlaams-Brabant, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Dominique Bullens, Prof. Dr.

Role: CONTACT

dominique.bullens@kuleuven.be

0032016343801

Marleen Jannis

Role: CONTACT

marleen.jannis@uzleuven.be

0032016343801

Facility Contacts

Dominique Bullens, Prof. Dr.

Role: primary

dominique.bullens@kuleuven.be

0032 16 34 38 01

Marleen Jannis

Role: backup

marleen.jannis@uzleuven.be

0032 16 34 38 01

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

s67001

Identifier Type: -

Identifier Source: org_study_id