Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

Birch Pollen Allergy Clinical Trial

Official title:

Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01449786
• Other study ID #: TK01/2011
• Status: Completed
• Phase: Phase 2
• First received: October 5, 2011
• Last updated: April 12, 2017
• Start date: March 14, 2012
• Est. completion date: December 20, 2016

Study information

• Verified date: April 2017
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

More than 70% of birch pollen allergic patients suffer from allergic reactions to certain foods, e.g. stone fruits, hazelnut and some vegetables. However, specific immunotherapy (SIT) with birch pollen extract is not effective for the treatment of associated food allergy in a substantial number of patients. Based on our previous clinical and immunological investigations of birch pollen related food allergy (BPRFA) the investigators hypothesize that for effective SIT of this abundant food allergy the disease-eliciting food allergens should be employed. To prove this concept, the investigators aim to sublingually administer the major apple allergen, Mal d 1, to birch pollen-allergic patients with concomitant apple allergy and evaluate clinical and immunological effects of this treatment. The investigators choose Mal d 1 as model food allergen because (i) its cross-reactivity with Bet v 1 has been well characterized,(ii) apple is the most frequent trigger for BPRFA and (iii) recombinant(r)Mal d 1 was well tolerated after sublingual administration to 20 birch pollen-allergic patients in a previous study. Sublingual administration of a defined concentration of GMP-rMal d 1 will be compared with equal doses of GMP-rBet v 1 as a positive control and placebo-treatment. Clinical parameters will include skin prick tests (SPT) and objective and subjective assessment of apple and birch pollen-induced allergic symptoms. Immunological parameters will comprise the analysis of antibody and T cell responses to Mal d 1 and Bet v 1 as well as the evaluation of basophil activation.

The proposed pilot study will be a first investigation of the concept to specifically treat BPRFA with the involved food allergens and thus, represents an important step in the development of an efficient and safe therapy in the future.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 20, 2016
• Est. primary completion date: February 28, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• otherwise healthy persons between 18 und 50 years of age;

• positive history of rhinoconjunctivitis to birch pollen

• oral allergy syndrome(OAS) to apple

• positive skin prick test (SPT) reaction to birch pollen and apple

• specific IgE for Bet v 1 and Mal d 1

Exclusion Criteria:

• Exclusion criteria

• Persons who due to their physical or mental state are not able to provide informed consent.

• Persons with underlying illnesses such as severe cardiopulmonary, malignant and/or autoimmune diseases

• Persons suffering from Hyper-IgE syndrome

• Persons receiving SIT during the past 5 years

• persons suffering from severe allergic reactions to apple such as generalized urticaria, asthma and/or anaphylaxis

• persons suffering from severe bronchial asthma to birch pollen

• persons suffering from pathological alterations of the lips and oral mucosa

• persons who are prescribed a treatment with immune-suppressive drugs, anti-histamines, leukotriene-antagonists or psychotropic drugs with anti-histaminic effects

• persons using ß-blockers

• Pregnant woman

Related Conditions & MeSH terms

• Birch Pollen Allergy
• Birch Pollen Related Apple Allergy
• Hypersensitivity
• Rhinitis, Allergic, Seasonal

Intervention

Drug:
• rMal d 1
25 µg daily as sublingually administered drops, 16 weeks
• rBet v 1
25 µg daily administered sublingually as drops over 16 weeks

Other:
• placebo drops
25 µg of placebo Drops daily administered sublingually over 16 weeks

Locations

Country	Name	City	State
Austria	Medical University of Vienna	Vienna

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of Vienna	Austrian Science Fund (FWF)

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test)	To measure the clinical effects on apple-induced OAS, open food challenges (OFC) with every 30 minutes increasing doses of GMP-rMal d 1 will be performed before and after the treatment period.	1 year
Secondary	T cell proliferation and cytokine production as a measure of tolerance induction	PBMC isolated from heparinised blood before, during and after sublingual administration of the treatment will be stimulated with titrated concentrations of rMal d 1 and rBet v 1, respectively. Proliferative and cytokine responses will be determined.	1 year
Secondary	allergen specific antibody response	measurement of IgE, IgG and IgA antibodies specific for Bet v 1 and Mal d 1	1