Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy
![]() |
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
ClinicalTrials.gov Identifier: NCT01449786 |
Recruitment Status
:
Completed
First Posted
: October 10, 2011
Last Update Posted
: April 13, 2017
|
- Study Details
- Tabular View
- No Results Posted
- Disclaimer
- How to Read a Study Record
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 or disease | Intervention/treatment | 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 (Clinical Trial) |
Actual Enrollment : | 60 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
Official Title: | Sublingual Immunotherapy of Birch Pollen Associated Apple Allergy |
Actual Study Start Date : | March 14, 2012 |
Actual Primary Completion Date : | February 28, 2014 |
Actual Study Completion Date : | December 20, 2016 |

Arm | Intervention/treatment |
---|---|
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
|
- 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.
- 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

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, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years to 65 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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01449786
Austria | |
Medical University of Vienna | |
Vienna, Austria, 1090 |
Principal Investigator: | Barbara Bohle, PhD, Prof. | Medical University of Vienna | |
Principal Investigator: | Tamar Kinaciyan, MD | Medical University of Vienna |
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 |
First Posted: | October 10, 2011 Key Record Dates |
Last Update Posted: | April 13, 2017 |
Last Verified: | April 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 |