Clinical trial NCT03744325: Immune Responses in Hen's Egg Oral Immunotherapy
Official title: Humoral and Cellular Immune Responses in Hen's Egg Oral Immunotherapy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Food Allergy
Egg Protein Allergy
Immune Tolerance
Keywords: Food allergy
Hen's egg allergy
Desensitization
Oral immunotherapy (OIT)
Systems biology
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: University of Helsinki
First posted: 2018-11-16
Enrollment: 50
Sex: ALL
Minimum age (years): 6
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention 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.
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: OIT-induced allergen-specific antibody responses
timeFrame: Up to 32 weeks
measure: OIT-induced changes in the peripheral blood cell transcriptome
timeFrame: Up to 32 weeks
measure: OIT-induced allergen-specific expression profiles of messenger-RNAs and microRNAs
timeFrame: Up to 32 weeks
Secondary outcomes:
measure: The prorportion of participants able to consume 1000mg of egg protein after 32 weeks of OIT
timeFrame: Up to 32 weeks
Other outcomes:
Locations:
Study officials:
affiliation: Skin and Allergy Hospital, Helsinki University Central Hospital
name: Mika J Mäkelä, Professor
role: STUDY_DIRECTOR
References: