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Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

This study has been completed.
Sponsor:
Collaborator:
Austrian Science Fund (FWF)
Information provided by (Responsible Party):
Tamar Kinaciyan, MD, Medical University of Vienna
ClinicalTrials.gov Identifier:
NCT01449786
First received: October 5, 2011
Last updated: April 12, 2017
Last verified: April 2017
  Purpose

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: Participant, Investigator
Primary Purpose: Treatment
Official Title: Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy

Resource links provided by NLM:


Further study details as provided by Tamar Kinaciyan, MD, 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.

  • allergen specific antibody response [ Time Frame: 1 ]
    measurement of IgE, IgG and IgA antibodies specific for Bet v 1 and Mal d 1


Enrollment: 60
Actual Study Start Date: March 14, 2012
Study Completion Date: December 20, 2016
Primary Completion Date: February 28, 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: treatment with rMal d 1
these apple and birch pollen allergic patients are treated with daily sublingual application of 25µg recombinant Major apple allergen, Mal d 1 during 4 months
Drug: rMal d 1
25 µg daily as sublingually administered drops, 16 weeks
Active Comparator: treatment with rBet v 1
These apple and birch pollen allergic patients are treated with daily sublingual application of 25µg recombinant Major birch pollen allergen,Bet v 1 during 4 months
Drug: rBet v 1
25 µg daily administered sublingually as drops over 16 weeks
Placebo Comparator: treatment with placebo drops
These apple and birch pollen allergic patients are treated daily with placebo applied sublingually during 4 months
Other: placebo drops
25 µg of placebo Drops daily administered sublingually over 16 weeks

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01449786

Locations
Austria
Medical University of Vienna
Vienna, Austria, 1090
Sponsors and Collaborators
Medical University of Vienna
Austrian Science Fund (FWF)
Investigators
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
ClinicalTrials.gov Identifier: NCT01449786     History of Changes
Other Study ID Numbers: TK01/2011
Study First Received: October 5, 2011
Last Updated: April 12, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tamar Kinaciyan, MD, Medical University of Vienna:
Mal d 1, Bet v 1, sublingual immunotherapy,

Additional relevant MeSH terms:
Hypersensitivity
Rhinitis, Allergic, Seasonal
Immune System Diseases
Rhinitis, Allergic
Rhinitis
Nose Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Otorhinolaryngologic Diseases
Hypersensitivity, Immediate

ClinicalTrials.gov processed this record on August 16, 2017