Nut Allergy Study: Double-blind Challenge and Oral Desensitization

Nut Allergy Study: Improving Diagnosis And Treatment Of Nut Allergy

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.

Study Overview

• Status: Completed
• Conditions: Nut Allergy
• Intervention / Treatment: Dietary supplement: Nut challenge; Dietary supplement: Nut challenge: Placebo; Dietary supplement: Nut oral desensitization

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 Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital, Skin and Allergy Hospital
  • Helsinki, Finland, 160
    • Helsinki University Central Hospital, Skin and Allergy Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Dietary supplement: Nut challenge; Nut powder made from non-roasted nuts and roasted banana mixed with oats yoghurt or chocolate pudding; Other Names: Super nuts banan chips; Yosa oat yoghurt; Arla cowpower chololate pudding
Placebo Comparator: Nut challenge: Placebo; See intervention	Dietary supplement: Nut challenge: Placebo; Dried banana mixed with oat yoghurt or chocolate pudding; Other Names: Super nuts banan chips; Yosa oat yoghurt; Arla cowpower chololate pudding
Experimental: 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.	Dietary supplement: Nut oral desensitization; Roasted peanut powder mixed with milk- and soy-free margarine; Other Names: Old Virginia Byrd Mill Fat-Light roasted peanut; Keiju-margarine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Helsinki University Central Hospital
• Investigators: Principal Investigator: Mika J Mäkelä, MD, PhD, Helsinki UCH

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): March 1, 2016

Study Registration Dates

• First Submitted: May 27, 2011
• First Submitted That Met QC Criteria: December 30, 2011
• First Posted (Estimate): January 2, 2012

Study Record Updates

• Last Update Posted (Estimate): September 13, 2016
• Last Update Submitted That Met QC Criteria: September 12, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: Nut allergy; Double-blind placebo-controlled (DBPC) oral nut challenge; Nut oral immunotherapy (OIT); Nut oral desensitization
• Additional Relevant MeSH Terms: Immune System Diseases; Food Hypersensitivity; Hypersensitivity, Immediate; Nut and Peanut Hypersensitivity; Hypersensitivity; Nut Hypersensitivity; Anti-Infective Agents; Anti-Bacterial Agents; Cefpodoxime; Cefpodoxime proxetil
• Other Study ID Numbers: HUCHT101060080; IAS11 (Registry Identifier: HUCH, Skin and Allergy Hospital)