Tolerance induction through non-avoidance to prevent persistent food allergy (TINA) in children and adults with peanut or tree nut allergy: rationale, study design and methods of a randomized controlled trial and observational cohort study
Valérie Trendelenburg,
Sabine Dölle-Bierke,
Nathalie Unterleider,
Aikaterina Alexiou,
Birgit Kalb,
Lara Meixner,
Stephanie Heller,
Susanne Lau,
Young- Ae Lee,
Florent Fauchère,
Julian Braun,
Magda Babina,
Sabine Altrichter,
Till Birkner,
Stephanie Roll,
Josefine Dobbertin-Welsch,
Margitta Worm,
Kirsten Beyer
Affiliations
Valérie Trendelenburg
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Sabine Dölle-Bierke
Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu
Nathalie Unterleider
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Aikaterina Alexiou
Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu
Birgit Kalb
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Lara Meixner
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Stephanie Heller
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Susanne Lau
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Young- Ae Lee
Max Delbrück Center For Molecular Medicine in the Helmholtz Association, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Florent Fauchère
Si-M / “Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin
Julian Braun
Si-M / “Der Simulierte Mensch” a science framework of Technische Universität Berlin and Charité - Universitätsmedizin Berlin
Magda Babina
Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu
Sabine Altrichter
Division of Dermatological Allergy, Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Till Birkner
Experimental and Clinical Research Center, a cooperation between the Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association and the Charité - Universitätsmedizin
Stephanie Roll
Institute for Epidemiology, Social Medicine and Health Economics, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Josefine Dobbertin-Welsch
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Margitta Worm
Division of Allergy and Immunology, Department of Dermatology, Venerology and Allergy, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu
Kirsten Beyer
Department of Pediatric Respiratory Medicine, Immunology and Critical Care Medicine, Charité – Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin
Abstract Background Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. Methods The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1–67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. Discussion This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. Trial registration German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de .
