Nut Allergy Study: Double-blind Challenge and Oral Desensitization

Study Overview
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Brief Summary
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Nut sensitization in skin prick tests is common in areas, including Finland, where birch pollen is abundant. However, sensitization to nuts in skin prick test does not predict the possibility of allergic symptoms when nuts are ingested. In this study the investigators launch and perform double-blind placebo-controlled nut challenges and oral desensitization/ protocol to those with serious symptoms in the challenge. The efficacy and safety of the new oral desensitization program is the primary outcome. The effect of oral desensitization on bronchial hyperreactivity, eosinophilic airway inflammation, and quality of life are secondary outcomes.

Detailed Description
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The investigators aim to improve nut allergy diagnosis by launching a new double-blind placebo-controlled nut (peanut, hazel nut, cashew) challenge protocol. The investigators also launch a specific oral tolerance induction (SOTI) protocol to nuts in serious nut allergy. This study takes place in the Helsinki University Skin and Allergy Hospital between May 2011 and December 2015. Inclusion criteria: age 6 to 18 years and suspected nut allergy (unclear anaphylaxis possibly caused by nuts, skin prick test to nuts ≥ 10 mm or specific-IgE ≥ 20 kU/L and have never eaten nuts, or avoids nuts and does not dare try nuts at home). Patients having uncontrolled asthma or other lung disease, having cardiovascular disease or other systemic disease, using beta-blockers, and having poor compliance, are excluded. Methods:The investigators perform skin prick tests to peanut, tree nuts and seeds, take a blood sample before the double-blind placebo-controlled food challenges (DBPCFC), and measure total IgE and specific-IgE to birch, peanut, hazel nut, allergen components Ara h 1, 2, 3, and 8, and Cor a 1 and 8. Then the serum samples are kept frozen for further component and immunologic analyses. The investigators put iv before the challenge. In DBPCFC the patients receive 5 mg, 50 mg, 200mg, and 1000mg nut protein mixt with placebo, or placebo every 30 minutes. The severity of the allergic reaction is estimated using a modified severity scale. The probability of severe/moderate reaction at low (<0.7 kU/L) and at increased (>0.7 kU/L) Ara h 2 and 8 concentrations is the primary end-point in the DBPCFC. The investigators also correlate the concentrations of Ara h 2 with the severity score. Patients with moderate or severe reaction in the challenge will be offered desensitization therapy SOTI using(pea)nut flour mixed with milk-free margarine. The first dose of 0.1 mg nut protein is given at hospital part of the up-dosing is made at home every 2 weeks. The patient takes an antihistamine 1 hour before each daily dose. An epinephrine autoinjector and prednisolone tablets are also prescribed for emergency use. The desensitization protocol takes 28 weeks and is personalized when needed. Exercise is avoided 1 hour following each dose. Before and after the SOTI the investigators measure food related quality of life using standardized questionnaires, and perform metacholine challenge and measure exhaled nitric oxid. After the SOTI the investigators take blood samples and perform DBPCFC again.

Official Title
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Nut Allergy Study: Improving Diagnosis And Treatment Of Nut Allergy

Conditions
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Nut Allergy

Intervention / Treatment
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* Dietary Supplement: Nut challenge
* Dietary Supplement: Nut challenge: Placebo
* Dietary Supplement: Nut oral desensitization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: sensitization in skin prick test or in serum nut-specific IgE unknown anaphylaxis suspected caused by nuts never eaten nuts if challenge positive with serious symptoms, OIT Exclusion Criteria: active asthma and low lung function, pregnancy, cardiovascular or other disease that might worsen during the challenge and OIT

Ages Eligible for Study
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Minimum Age: 3 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: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Nut challenge<br>Double-blind placebo controlled oral challenge 5-50-200-1000 mg peanut or hazelnut protein, or placebo administered with 30 min intervals and 2 hour-follow-up after the last dose. | Dietary Supplement: Nut challenge<br>* Nut powder made from non-roasted nuts and roasted banana mixed with oats yoghurt or chocolate pudding<br>* Other names: Arla cowpower chololate pudding;|
| Placebo Comparator: Nut challenge: Placebo<br>See intervention | Dietary Supplement: Nut challenge: Placebo<br>* Dried banana mixed with oat yoghurt or chocolate pudding<br>* Other names: Arla cowpower chololate pudding;|
| Experimental: Nut oral desensitization<br>Patients who have moderate to severe immediate allergic reaction at peanut challenge and who enter the oral desensitization program receive peanut protein daily, from 0,1 mg to 800 mg peanut protein, maintenance dose 800 mg. | Dietary Supplement: Nut oral desensitization<br>* Roasted peanut powder mixed with milk- and soy-free margarine<br>* Other names: Keiju-margarine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of nut oral desensitization | Change from baseline in the amount of nut (mg) tolerated in a double-blind placebo-controlled oral challenge at 1 month after the 6-month oral desensitization therapy. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of the treatment on quality of life | Change from baseline in Quality of life questionnaire square before and after the oral desensitization therapy | 7 months | 
| Effect of the treatment on bronchial hyperreactivity and airway inflammation | Change from baseline in bronchial hyperreactivity in metacholine challenge and in eosinophilic airway inflammation measured by multiple channel exhaled nitric oxid | 1 year | 
| Safety of nut oral desensitization therapy | Number of participants with adverse events as a measure of safety and tolerability | 7 months | 
| Effect of the treatment on eosinophilic airway inflammation | Change from baseline in exhaled nitric oxid concentration | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nut allergy, Double-blind placebo-controlled (DBPC) oral nut challenge, Nut oral immunotherapy (OIT), Nut oral desensitization