Immune Responses in Hen's Egg Oral Immunotherapy

Food Allergy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03744325
• Other study ID #: HOIT01
• Status: Active, not recruiting
• Phase: N/A
• Start date: March 18, 2014
• Est. completion date: December 31, 2020

Study information

• Verified date: November 2018
• Source: Helsinki University Central Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: December 31, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 19 Years

Eligibility

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

Related Conditions & MeSH terms

• Egg Protein Allergy
• Food Allergy
• Food Hypersensitivity
• Hypersensitivity
• Immune Tolerance

Intervention

Dietary Supplement:
• Hen's egg OIT
Increasing doses of egg white protein administered orally

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Helsinki University Central Hospital	Helsinki University

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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