Introduction: Children with peanut allergy are at increased risk of developing tree nut allergies, which can be severe and for most lifelong. Introduction of peanut in the first year of life can reduce the risk of peanut allergy, however, prevention strategies for tree nut allergies have not been established. We aimed to test the efficacy and safety of a novel strategy, a supervised multi-nut oral food challenge (OFC) compared to standard care for tree nut allergy prevention in infants at high risk of developing tree nut allergy, TreEAT. Methods and analysis: TreEAT is a 2-armed, open-label, randomised, controlled trial (RCT). Infants (n=212) aged 4-11months with peanut allergy will be randomised 1:1 at peanut allergy diagnosis to either a hospital-based multi-tree nut (almond, cashew, hazelnut and walnut) OFC using multi-nut butter or standard care (home introduction of individual tree nuts). All infants will be assessed at age 18months, with questionnaires and SPT to peanut and tree nuts. Peanut and tree nut OFCs will be performed as required to determine allergy status for each nut. The primary outcome is tree nut allergy at age 18 months. Secondary outcomes include peanut allergy resolution, proportion and severity of adverse events related to tree nut ingestion, number and frequency of tree nuts ingested, quality of life and parental anxiety and allergy related healthcare visits from randomisation to 18 months of age. Analyses will be performed on an intention-to-treat basis. Ethics and dissemination TreEAT was approved by the Royal Children’s Hospital Human Research Ethics Committee (#70489). Outcomes will be presented at scientific conferences and disseminated through publication. Trial registration number: ClinicalTrials.gov ID: NCT04801823

Background: Combined treatment with probiotic and peanut oral immunotherapy (PPOIT) was shown to induce sustained unresponsiveness (SU) in a proof-of-concept randomized trial. Additional data on safety and long-term outcomes are needed. This study aimed to evaluate the safety and long-term effects of PPOIT in children with peanut allergy. Methods: Open-label study of 20 children aged 1-12 years with challenge-confirmed peanut allergy; all children received 18-months of PPOIT. Efficacy endpoints were desensitization, 8-week SU, and persistence of 8-week SU at 3-years post-treatment, assessed by double-blind placebo-controlled food challenge (cumulative 4950mg peanut protein). Treatment emergent adverse events and relationship to study treatment were recorded. Immunologic measures and health related quality of life (HRQL) were evaluated at screening, end-of-treatment and 3-years post-treatment. Results: Sixteen children (75%) completed treatment. By intention-to-treat analysis, 75% (15/20) achieved desensitization and 60% (12/20) achieved 8-week SU. Ten of 12 participants with SU at end-of-treatment consented to the 3-year SU challenge; 6 (60%) had persistence of SU. PPOIT was associated with significantly reduced peanut skin prick test wheal size and serum peanut specific-IgE levels at end-of-treatment, 12-months and 3-years post-treatment. There were no serious adverse events. HRQL scores improved (exceeding the Minimal Clinically Important Difference of 0.45) at 12-months post-treatment with benefit sustained at 3-years post-treatment. Conclusions: Eighteen months of PPOIT induced high rates of desensitization and SU, and SU persisted to 3-years post-treatment in a majority of initial responders. PPOIT led to long-lasting suppression of peanut sIgE and long-lasting clinically important improvement in HRQL.