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
Creators: name: Trendelenburg, Valérie
name: Dölle-Bierke, Sabine
name: Unterleider, Nathalie
name: Alexiou, Aikaterina
name: Kalb, Birgit
name: Meixner, Lara
name: Heller, Stephanie
name: Lau, Susanne
name: Lee, Young- Ae
name: Fauchère, Florent
name: Braun, Julian
name: Babina, Magda
name: Altrichter, Sabine
name: Birkner, Till
name: Roll, Stephanie
name: Dobbertin-Welsch, Josefine
name: Worm, Margitta
name: Beyer, Kirsten
Publisher: name: Charité - Universitätsmedizin Berlin
Year: 2022
Subjects: subject: Protocol
subject: Randomized controlled trial
subject: Peanut allergy
subject: Tree nut allergy
subject: Elimination diet
subject: Higher threshold
subject: Oral tolerance
subject: Persistent food allergy
subject: 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit

description: 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 &gt;= 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.