Clinical trial NCT01502878: Nut Allergy Study: Double-blind Challenge and Oral Desensitization
Official title: Nut Allergy Study: Improving Diagnosis And Treatment Of Nut Allergy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nut Allergy
Keywords: Nut allergy
Double-blind placebo-controlled (DBPC) oral nut challenge
Nut oral immunotherapy (OIT)
Nut oral desensitization
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
First posted: 2012-01-02
Enrollment: 102
Sex: ALL
Minimum age (years): 3
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy of nut oral desensitization
timeFrame: 7 months
Secondary outcomes:
measure: Effect of the treatment on quality of life
timeFrame: 7 months
measure: Effect of the treatment on bronchial hyperreactivity and airway inflammation
timeFrame: 1 year
measure: Safety of nut oral desensitization therapy
timeFrame: 7 months
measure: Effect of the treatment on eosinophilic airway inflammation
timeFrame: 1 year
Other outcomes:
Locations:
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Skin and Allergy Hospital
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Skin and Allergy Hospital
Study officials:
affiliation: Helsinki UCH
name: Mika J Mäkelä, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Uotila R, Kukkonen AK, Greco D, Pelkonen AS, Makela MJ. Peanut oral immunotherapy decreases IgE to Ara h 2 and Ara h 6 but does not enhance sensitization to cross-reactive allergens. J Allergy Clin Immunol. 2017 Apr;139(4):1393-1396.e6. doi: 10.1016/j.jaci.2016.09.054. Epub 2016 Dec 1. No abstract available.