Improved Diagnostics in Food Allergy Study

Study Overview
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Brief Summary
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The investigators will conduct low-dose intranasal allergen challenges on children and young people with an indeterminate diagnosis of food allergy to cow's milk or peanut. Blood samples will also be taken, for conventional blood allergy diagnostics (allergy-specific Immunoglobulin E) and mast cell activation test (MAT). The data will be used to determine the diagnostic accuracy of two complementary, novel approaches to diagnose food allergy, in a representative clinical cohort.

Official Title
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Improved Diagnostics in Food Allergy (ID-in-FA) Study

Conditions
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Food Allergy

Intervention / Treatment
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* Diagnostic Test: Intranasal food challenge
* Diagnostic Test: Mast cell activation test


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: IgE-sensitisation to peanut, (hen's) egg or cow's milk, with indeterminate clinical (allergy) status, defined as IgE-sensitisation below 95% positive predictive value (PPV) for diagnosis for either allergen-specific IgE or SPT, using published cut-offs OR clinician suspicion of tolerance (on basis of clinical history) despite IgE sensitisation >95% PPV cut-offs. Written informed consent from parent/guardian, with assent from children aged 6 years and above wherever possible. Participants aged over 16 years will need to provide their own informed consent. Exclusion Criteria: Acute illness or current unstable asthma, defined as: Febrile ≥38.0oC in last 72 hours Acute wheeze in last 72 hours requiring treatment Recent admission to hospital in preceding 2 weeks for acute asthma Current medication Asthma reliever medication required in preceding 72 hours Recent administration of a medicine containing antihistamine within the last 3 days Current oral steroid for asthma exacerbation or course completed within last 2 weeks Unwilling or unable to fulfil study requirements

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 18 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Peanut<br>Participants with possible allergy to peanut | Diagnostic Test: Intranasal food challenge<br>* Subjects will undergo an incremental intranasal challenge to initially 0.9% NaCl saline solution, and then increasing doses of the food protein<br>Diagnostic Test: Mast cell activation test<br>* Blood will be processed for mast cell activation as previously described (https://doi.org/10.1016/j.jaci.2018.01.043)<br>|
| Experimental: Cow's Milk<br>Participants with possible allergy to cow's milk | Diagnostic Test: Intranasal food challenge<br>* Subjects will undergo an incremental intranasal challenge to initially 0.9% NaCl saline solution, and then increasing doses of the food protein<br>Diagnostic Test: Mast cell activation test<br>* Blood will be processed for mast cell activation as previously described (https://doi.org/10.1016/j.jaci.2018.01.043)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Test performance | Comparison of test performance characteristics (sensitivity, specificity, measured according to standard statistical methods) for each of the following diagnostic tests, compared to a formal oral food challenge (FC) as the reference standard: i. Intranasal FC (InFC) ii. Skin prick testing iii. Characterisation of serum-specific IgE to whole allergen, components and molecular components iv. Mast cell activation test (MAT) v. Basophil activation test (BAT) (peanut only) | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Number of participants who experience a non-allergic adverse event, and/or have symptoms of a systemic allergic reaction) associated with the intranasal food challenge. | 1 day |