Study Protocol Evaluating Hydrolyzed Rice Protein Formula Safety in Infants With Cow's Milk Allergy

Hydrolyzed rice formulas (HRF) are a suitable option for the nutritional management of non-breastfed children with cow’s milk allergy (CMA). Human milk oligosaccharides (HMOs) enhance gastrointestinal health, promote the growth of beneficial gut microbiota, and may reduce the incidence of infections and antibiotic use. There is currently no evidence regarding the hypoallergenicity of HRF containing HMOs. The purpose of this study is to demonstrate the hypoallergenicity of a new hydrolyzed rice protein-based formula containing two manufactured HMOs (HRF-HMO). RIGHT-HY is a multi-center randomized controlled study enrolling infants and children (60 days–3 years) with documented Immunoglobulin E-mediated CMA. Children will be randomized in a crossover fashion to double-blind placebo-controlled food challenges (DBPCFC) with HRF-HMO and an amino acid-based formula (AAF)-HMO, followed by a 7-days open challenge with HRF-HMO requiring a daily minimum intake of 240 ml. Both formulas contain 2-fucosyllactose and lacto-N-neotetraose (1.5 g/L). The primary objective is to demonstrate with 95% confidence that 90% of children with CMA do not develop allergic reactions to HRF-HMO under DBPCFC conditions. Up to 67 children will be enrolled to meet the hypoallergenicity criteria. This sample size allows for a 10% drop-out rate and occurrence of one allergic reaction. An interim analysis will be performed after 42 children have completed both food challenges to assess whether hypoallergenicity criteria have been met, in which case, the study will be stopped for success. Secondary endpoints include HRF-HMO intake and gastrointestinal tolerance during the week-long open challenge, and adverse events throughout the study. The RIGHT-HY study was approved by ethical committees of all participating sites. This study will be the first to generate robust evidence on the hypoallergenicity of this rice formula with added HMOs in children with CMA. The results of the study will be disseminated in peer-reviewed publications and presentations at scientific conferences.Study protocol registrationhttps://clinicaltrials.gov/study/NCT06633289, identifier NCT06633289.