Study Protocol - Impact of Lactobacillus rhamnosus GG on Allergic Reactions and Gut Microbiota Composition in Children with Cow’s Milk Allergy A Single-Center, Randomized, Double-Blinded, Placebo-Controlled, Phase II – MILK ALLERGY Trial

Abstract

Background: IgE-mediated reactions constitute 70% of cow's milk-induced allergic reactions (AR). There is no established treatment. Recent evidence suggests that immunomodulation with probiotics represents a safe novel strategy, influencing immunity and inducing tolerance to milk protein antigens by action on human gut microbiota. Current evidence focuses most on the infant population. Objective: We will study the impact of Lactobacillus rhamnosus GG (LGG), compared to placebo, as an effective agent to improve ARs upon exposure to cow's milk in children from 5 to 10 years of age. Methods: This will be a phase II, single-center, randomized, double-blinded, placebo-controlled study, where a total of 200 participants will be treated for 12 months, with either; LGG or placebo, randomly allocated at 1:1. A double-blinded placebo-controlled food challenge (DBPCFC) with cow's milk will be used before and after the intervention. Results will be graded using the PRACTALL scoring system. The primary outcome will be binary – 'passing' by the absence of any AR, or a decrease from the baseline results or 'not passing' the DBPCFC after treatment. Secondary outcomes will include covariate adjustment and subgroup analysis by affected body systems and severity of ARs. Secondary analyses will include a comparison of the proportions of the taxonomic composition of gut microbiota, and quality of life, with baseline measurements. Conclusion: This trial will contribute to filling knowledge gaps about cow's milk allergy management using LGG in this specific population as an affordable and accessible non-pharmacological agent with few recorded side effects. If proven to be efficacious, it has the potential to decrease the worldwide prevalence of CMA and the resulting systemic, familial, and personal burdens.