Standardization of double blind placebo controlled food challenge with soy within a multicentre trial

R Treudler; A Franke; A Schmiedeknecht; B K Ballmer-Weber; M Worm; T Werfel; U Jappe; T Biedermann; J Schmitt; R Brehler; A Kleinheinz; J Kleine-Tebbe; H Brüning; F Ruëff; J Ring; J Saloga; K Schäkel; T Holzhauser; St Vieths; J C Simon

doi:10.1186/s13601-016-0129-4

Standardization of double blind placebo controlled food challenge with soy within a multicentre trial

Clin Transl Allergy. 2016 Nov 7:6:39. doi: 10.1186/s13601-016-0129-4. eCollection 2016.

Authors

R Treudler¹, A Franke², A Schmiedeknecht², B K Ballmer-Weber³, M Worm⁴, T Werfel⁵, U Jappe⁶, T Biedermann⁷, J Schmitt⁸, R Brehler⁹, A Kleinheinz¹⁰, J Kleine-Tebbe¹¹, H Brüning¹², F Ruëff¹³, J Ring¹⁴, J Saloga¹⁵, K Schäkel¹⁶, T Holzhauser¹⁷, St Vieths¹⁷, J C Simon¹

Affiliations

¹ Department of Dermatology, Venerology and Allergology, Universität Leipzig, Leipzig, Germany ; Leipziger Interdisziplinäres Centrum für Allergologie (LICA) - Comprehensive Allergy Centre (CAC), Klinik für Dermatologie, Venerologie und Allergologie, Universitätsklinikum Leipzig, Philipp-Rosenthal-Straße 23, 04103 Leipzig, Germany.
² Clinical Trial Centre Leipzig (ZKS), Universität Leipzig, Leipzig, Germany.
³ Allergy Unit, Department of Dermatology, University Hospital Zürich, Zurich, Switzerland.
⁴ Allergy Center Charité, Department of Dermatology, Venerology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
⁵ Department of Dermatology and Allergology, MH Hannover, Hannover, Germany.
⁶ Division of Clinical and Molecular Allergology Research Center Borstel, Airway Research Center North (ARCN), Borstel, Germany ; Department of Internal Medicine, University of Lübeck, Lübeck, Germany.
⁷ Department of Dermatology, Universität Tübingen, Tübingen, Germany ; Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.
⁸ Department of Dermatology, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany ; Center for Evidence-Based Healthcare, Medical Faculty Carl Gustav Carus, TU Dresden, Dresden, Germany.
⁹ Department of Dermatology, Universität Münster, Münster, Germany.
¹⁰ Department of Dermatology, Elbekliniken Buxtehude, Buxtehude, Germany.
¹¹ Allergy- and Asthma Centre Westend, Berlin, Germany.
¹² Day Care Clinic for Allergy and Dermatology, Kiel, Germany.
¹³ Department of Dermatology and Allergology, Ludwig-Maximilian University, Munich, Germany.
¹⁴ Department of Dermatology and Allergology, Technical University Munich, Munich, Germany.
¹⁵ Department of Dermatology, University Medical Center, Johannes Gutenberg-University, Mainz, Germany.
¹⁶ Department of Dermatology, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany.
¹⁷ Division of Allergology, Paul-Ehrlich-Institut, Langen, Germany.

Abstract

Background: Multicentre trials investigating food allergies by double blind placebo controlled food challenges (DBPCFC) need standardized procedures, challenge meals and evaluation criteria. We aimed at developing a standardized approach for identifying patients with birch related soy allergy by means of DBPCFC to soy, including determination of threshold levels, in a multicentre setting.

Methods: Microbiologically stable soy challenge meals were composed of protein isolate with consistent Gly m 4 levels. Patients sensitized to main birch allergen Bet v 1 and concomitant sensitization to its soy homologue Gly m 4 underwent DBPCFC. Outcome was defined according to presence and/or absence of ten objective signs and intensity of eight subjective symptoms as measured by visual analogue scale (VAS).

Results: 138 adult subjects (63.8% female, mean age 38 years) underwent DBPCFC. Challenge meals and defined evaluation criteria showed good applicability in all centres involved. 45.7% presented with objective signs and 65.2% with subjective symptoms at soy challenge. Placebo challenge meals elicited non-cardiovascular objective signs in 11.6%. In 82 (59.4%) subjects DBPCFC was judged as positive. 70.7% of DPBCFC+ showed objective signs and 85.4% subjective symptoms at soy challenge. Subjective symptoms to soy challenge meal in DBPCFC+ subjects started at significantly lower dose levels than objective signs (p < 0.001). Median cumulative eliciting doses for first objective signs in DBPCFC+ subjects were 4.7 g [0.7-24.7] and 0.7 g [0.2-4.7] total soy protein for first subjective symptoms (p = 0.01).

Conclusions: We present the hitherto largest group of adults with Bet v 1 and Gly m 4 sensitization being investigated by DBPCFC. In this type of food allergy evaluation of DBPCFC outcome should not only include monitoring of objective signs but also scoring of subjective symptoms. Our data may contribute to standardize DBPCFC in pollen-related food allergy in multicentre settings.

Trial registration: EudraCT: 2009-011737-27.

Keywords: Birch; DBPCFC; Food allergy; LOAEL; Methods; Soy.