Nut Allergy Study: Double-blind Challenge and Oral Desensitization

Not Applicable

Completed

• Conditions: Nut Allergy
• Interventions: Dietary Supplement: Nut challenge; Dietary Supplement: Nut oral desensitization

• Registration Number: NCT01502878
• Lead Sponsor: Helsinki University Central Hospital

Brief Summary

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

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.

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-05-27
• Study First Submitted QC: 2011-12-30
• Study First Posted: 2012-01-02
• Primary Completion: 2015-12
• Study Completion: 2016-03
• Status Verified: 2016-09
• Last Update Submitted: 2016-09-12
• Last Update Posted: 2016-09-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Nut challenge: Placebo	Nut challenge	See intervention
Nut challenge	Nut challenge	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.
Nut oral desensitization	Nut oral desensitization	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.

Primary Outcome Measures

Name	Time	Method
Efficacy of nut oral desensitization	7 months	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.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Helsinki University Central Hospital, Skin and Allergy Hospital; 🇫🇮 Helsinki, Finland