Skin Testing With Recombinant Bet v 1 and Hypoallergenic Recombinant Bet v 1 Fragments

Completed

• Conditions: Atopic Dermatitis
• Interventions: Other: SPT and APT

• Registration Number: NCT02098551
• Lead Sponsor: Stefan Woehrl

Brief Summary

Aim of this study is to use the major allergen 1 of birch-tree pollen (Bet v 1, Betula verrucosa, synonymous Betula pendula), to investigate the contribution of immunoglobulin E (IgE)- versus non-IgE-mediated mechanisms to chronic skin inflammation in atopic dermatitis patients.

Detailed Description

In this study non-IgE-reactive recombinant Bet v 1 (rBet v 1) fragments (F1: aa 1-74; F2: aa 75-160) and the fully IgE-reactive recombinant Bet v 1 (aa 1-160)will be used for skin prick testing and atopy patch testing in birch pollen allergic patients with birch pollen induced exacerbation of atopic dermatitis. For control purposes birch pollen allergic patients without birch pollen-induced atopic eczema, persons with allergies other than to birch and non-allergic people will be tested.

The individuals will be subjected to in vivo skin prick and atopy patch testing with rBet v 1, rBet v 1 fragment 1, rBet v 1 fragment 2 and an equimolar mix of the rBet v 1 fragments. In parallel, the IgE reactivity, and in vitro T cell proliferation, and cytokine production will be studied. Those analyses should help to determine the relevance of IgE mediated mechanisms to chronic skin inflammation and T cell proliferation in AD patients.

A staining for the surface markers chemokine receptor (CCR4)+ and cutaneous lymphocyte antigen (CLA)+ which reportedly are enriched in inflamed skin will further allow to investigate whether patients with high numbers of T lymphocytes expressing CCR4 and CLA tend to exhibit stronger skin inflammation. Moreover, allergen-specific antibody and T cell responses will be analyzed 6-8 weeks after the epicutaneous allergen application.

Study Timeline

• Study Start: 2011-02
• Study First Submitted: 2011-07-26
• Primary Completion: 2011-11
• Study Completion: 2013-04
• Study First Submitted QC: 2014-03-25
• Study First Posted: 2014-03-28
• Status Verified: 2015-12
• Last Update Submitted: 2015-12-06
• Last Update Posted: 2015-12-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Age between 18 and 75 years
2. They will be available to complete the study

Exclusion Criteria

1. Severe general maladies
2. Severe skin inflammation in the test area
3. Risk of non-controllable general reaction
4. Pregnancy and breast-feeding
5. Autoimmune diseases, immune-defects including immuno-suppression, immune-complex-induced immunopathies
6. Contra-indication for adrenaline
7. Patients under long-term treatment with systemic corticosteroids immunosuppressive drugs, tranquilizers or psychoactive drugs
8. Positive IgE reaction on hypoallergenic Bet v 1 derivatives
9. The subject is currently participating in another clinical study in which the subject is or will be exposed to an investigational or a non-investigational drug.
10. The subject is at risk of non-compliance with the study procedures/restrictions

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Four (4)	SPT and APT	Group 1: Birch pollen-related atopic dermatitis (AD) (n=15) Group 2: Birch pollen allergic patients without AD (n=5) Group 3: Allergic individuals without birch pollen allergy (n=5) Group 4: Non-allergic individuals (n=5) Patients will be tested by SPT and APT: SPT: Histamine, buffer, commercial birch pollen extract, rBet v 1, rBet v 1 fragment 1, rBet v 1 fragment 2, and equimolar rBet v 1 fragment mix (20 and 40 μg/ml) in duplets. APT: birch pollen extract, rBet v 1, rBet v 1 fragment 1, rBet v 1 fragment 2, equimolar mix of rBet v 1 fragments (160 μg/application); negative control with vaseline

Primary Outcome Measures

Name	Time	Method
Number of Participants with Positive Atopy Patch Testing Reactions of Each Grade on the European Task Force on Atopic Dermatitis Scale	6 months	Birch pollen extract (BPE), as well as rBet v 1 (160mg), rBet v 1 fragment 1 (160mg), rBet v 1 fragment 2 (160mg), and an equimolar rBet v 1 fragment mix (80mg of each rBet v 1 fragment), were applied for 48h in patch test chambers onto nonlesional skin on the backs of the subjects. After 48h, patches were removed, and reactions were analyzed and photodocumented. Grading of positive APT reactions (i.e., reactions of more than 4 mm in diameter) was done according the European Task Force on Atopic Dermatitis by a blinded investigator: -, negative result; ?, only erythema, questionable; +, erythema, infiltration; ++, erythema, few papules (\<3); +++, erythema, papules from 4 to less than many; ++++, erythema, many or spreading papules; or +++++, erythema, vesicles.

Trial Locations

Locations (1)

Medical University of Vienna; 🇦🇹 Vienna, Austria