Immune Responses in Hen's Egg Oral Immunotherapy

Study Overview
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Brief Summary
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The study determines how a 6 months oral immunotherapy (OIT) program with hen's egg (HE) effects cellular and humoral immune responses in 50 children with HE allergy. Clinical data, transcriptomics and epigenetics are combined and analyzed by advanced system biology methods. This study will provide better understanding of the effects and mechanisms of OIT.

Detailed Description
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Oral immunotherapy (OIT) is a therapeutic approach, where gradually increasing doses of a specific food allergen are administered orally. OIT can desensitize up to 80% of children with persistent food allergy, and in a subset lead to sustained immune tolerance. The immunologic mechanisms induced by OIT are still poorly understood. In this randomized cross-over study, 50 children with challenge-confirmed hen's egg (HE) allergy will be randomized (2:1) to receive either active HE OIT or continue on an avoidance diet for 6 months after which active OIT is started. The immunological changes induced by OIT will be compared to the patient's initial status and to that of the patients on an avoidance diet. Serum antibody and humoral mediator analyses as well as gene expression of blood mononuclear cell (PBMC) by genome-wide microarray assays will be studied. PBMCs will be stimulated with HE allergens and innate immunity agonists, and the differences in the expression profiles of messenger-RNAs as well as microRNAs will be studied. Single-cell sequencing and sorting of regulator T cells (Tregs) will be performed focusing on their transcriptomic responses and gene methylation. Finally, clinical data, transcriptomics and epigenetic changes will be combined and analyzed by advanced system biology methods. This study will provide better understanding of the effects and mechanisms of OIT and identify biomarkers for selection of patients benefitting from personalized OIT.

Official Title
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Humoral and Cellular Immune Responses in Hen's Egg Oral Immunotherapy

Conditions
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Food Allergy, Egg Protein Allergy, Immune Tolerance

Intervention / Treatment
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* Dietary Supplement: Hen's egg OIT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 6-19 years Sensitization to egg white (egg white- specific IgE ≥0.35 kU/l or skin prick test ≥3 mm) Positive double-blind, placebo-controlled food challenge to heated egg white Exclusion Criteria: Poor adherence Uncontrolled or severe asthma Severe systemic illness Active autoimmune disease Active, malignant neoplasia

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Patients are randomized 2:1 to receive active HE OIT or continue on an elimination diet after which active HE OIT is started.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Hen's egg OIT<br>Daily intake of gradually increasing doses of egg white protein under a 32 weeks period, continued by regular, daily intake of 1000 mg egg white protein. | Dietary Supplement: Hen's egg OIT<br>* Increasing doses of egg white protein administered orally<br>|
| No Intervention: Hen's egg avoidance<br>Hen's egg is avoidance diet is continued. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| OIT-induced allergen-specific antibody responses | The amount of specific serum IgE, IgG4, and IgA antibodies (kU/L) to the major egg allergens (Gal d1 - d4) will be measured by ImmunoCAP after 0, 14, and 32 weeks of OIT or avoidance. | Up to 32 weeks | 
| OIT-induced changes in the peripheral blood cell transcriptome | Gene expression of blood mononuclear cells (PBMC) after 0, 14 and 32 weeks of OIT or avoidance will be studied. Total-RNA extracted from PBMCs will be used for microarrays. The genome-wide expression of the approximately 25.000 genes will be investigated on Agilent SurePrint G3 Human Gene Expression v3 arrays. | Up to 32 weeks | 
| OIT-induced allergen-specific expression profiles of messenger-RNAs and microRNAs | Comprehensive highthroughput sequencing for long (mRNA) and short (miRNA) coding gene expression approach will be used to investigate transcriptional changes in exposed blood cells after different stimulations (egg extract, LPS, PolyI:C) | Up to 32 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The prorportion of participants able to consume 1000mg of egg protein after 32 weeks of OIT | Measured in mg of egg protein consumed without symptoms | Up to 32 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Food allergy, Hen's egg allergy, Desensitization, Oral immunotherapy (OIT), Systems biology