Birch Pollen Allergy, Birch Pollen Related Apple Allergy
Conditions
Keywords
Mal d 1, Bet v 1, sublingual immunotherapy,
Brief 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.
Interventions
DRUGrMal d 1
25 µg daily as sublingually administered drops, 16 weeks
DRUGrBet v 1
25 µg daily administered sublingually as drops over 16 weeks
OTHERplacebo drops
25 µg of placebo Drops daily administered sublingually over 16 weeks
Sponsors
Austrian Science Fund (FWF)
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test) | 1 year | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| T cell proliferation and cytokine production as a measure of tolerance induction | 1 year | 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. |
| allergen specific antibody response | 1 | measurement of IgE, IgG and IgA antibodies specific for Bet v 1 and Mal d 1 |
Countries
Austria
Outcome results
None listed