Immune Responses in Hen's Egg Oral Immunotherapy

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

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.

Study Overview

• Status: Unknown
• Conditions: Food Allergy; Immune Tolerance; Egg Protein Allergy
• Intervention / Treatment: Dietary supplement: Hen's egg OIT

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 19 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 6-19 years
2. Sensitization to egg white (egg white- specific IgE ≥0.35 kU/l or skin prick test ≥3 mm)
3. Positive double-blind, placebo-controlled food challenge to heated egg white

Exclusion Criteria:

1. Poor adherence
2. Uncontrolled or severe asthma
3. Severe systemic illness
4. Active autoimmune disease
5. Active, malignant neoplasia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Hen's egg OIT; 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; Increasing doses of egg white protein administered orally
No Intervention: Hen's egg avoidance; Hen's egg is avoidance diet is continued.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Collaborators: University of Helsinki
• Investigators: Study Director: Mika J Mäkelä, Professor, Skin and Allergy Hospital, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2014
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): December 31, 2020

Study Registration Dates

• First Submitted: November 12, 2018
• First Submitted That Met QC Criteria: November 15, 2018
• First Posted (Actual): November 16, 2018

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: November 15, 2018
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: Desensitization; Food allergy; Systems biology; Oral immunotherapy (OIT); Hen's egg allergy
• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Food Hypersensitivity
• Other Study ID Numbers: HOIT01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No