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Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified October 2011 by Medical University of Vienna.
Recruitment status was:  Not yet recruiting
Austrian Science Fund (FWF)
Information provided by (Responsible Party):
Tamar Kinaciyan, MD, Medical University of Vienna Identifier:
First received: October 5, 2011
Last updated: October 7, 2011
Last verified: October 2011

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.

Condition Intervention Phase
Birch Pollen Related Apple Allergy
Birch Pollen Allergy
Drug: rMal d 1
Drug: rBet v 1
Other: placebo drops
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:

Further study details as provided by Medical University of Vienna:

Primary Outcome Measures:
  • allergen concentration to induce allergic reactions in the oral cavity as a measure of efficacy (oral provocation test) [ Time Frame: 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 Outcome Measures:
  • T cell proliferation and cytokine production as a measure of tolerance induction [ Time Frame: 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.

Estimated Enrollment: 60
Study Start Date: December 2011
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment with rMal d 1 Drug: rMal d 1
25 µg daily as sublingually administered drops, 16 weeks
Active Comparator: treatment with rBet v 1 Drug: rBet v 1
25 µg daily administered sublingually as drops over 16 weeks
Placebo Comparator: treatment with placebo Other: placebo drops
25 µg of placebo daily administered sublingually as drops over 16 weeks


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts 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:

  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01449786

Contact: Tamar Kinaciyan, MD +43 1 40400 ext 7704
Contact: Barbara Bohle, PhD, Prof. +43 1 40400 ext 5114

Medical University of Vienna Not yet recruiting
Vienna, Austria, 1090
Contact: Tamar Kinaciyan, MD    +43140400 ext 7704   
Contact: Barbara Bohle, PhD, Prof    +43140400 ext 5114   
Principal Investigator: Barbara Bohle, PhD, Prof.         
Principal Investigator: Tamar Kinaciyan, MD         
Sponsors and Collaborators
Medical University of Vienna
Austrian Science Fund (FWF)
Principal Investigator: Barbara Bohle, PhD, Prof. Medical University of Vienna
Principal Investigator: Tamar Kinaciyan, MD Medical University of Vienna
  More Information

Responsible Party: Tamar Kinaciyan, MD, MD, Ass.Prof., Medical University of Vienna Identifier: NCT01449786     History of Changes
Other Study ID Numbers: TK01/2011
Study First Received: October 5, 2011
Last Updated: October 7, 2011

Additional relevant MeSH terms:
Rhinitis, Allergic, Seasonal
Immune System Diseases
Rhinitis, Allergic
Nose Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Otorhinolaryngologic Diseases
Hypersensitivity, Immediate processed this record on March 24, 2017