Tolerance induction through early feeding to prevent food allergy in infants with eczema

• Applicant: Dr. Birgit Kalb
• Subject Area: Clinical Immunology and Allergology ; Pediatric and Adolescent Medicine
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 409525714

In order to prevent food allergy (FA) major achievements have been made in recent years, however, many issues are still unsolved. Therefore, we started in the 1st funding period a randomized placebo controlled trial (RCT) in infants with eczema with the hypothesis that early and continuous feeding of low but increasing amounts of allergens in parallel starting at 4-8 months of age is safe and will reduce FA at one year of age (cohort 1). Despite major restrictions due to the COVID 19 pandemic 44 infants were randomized until July 2022 and received a sugar-free rusk-like biscuit powder containing either hen’s egg (HE), cow’s milk (CM), peanut (PN) and hazelnut (HN) OR placebo in a 2:1 randomization. 36.4% of the infants were already sensitized to at least one of these allergens before starting the intervention, but only 2 children experienced mild cutaneous symptoms during intervention. So far, 24 children have performed the 1-year visit. In regard to the primary endpoint (IgE-mediated food allergy to one or more of the four foods) 2 children had an IgE-mediated food allergy. 15 children (63%) were not sensitized, 3 children were sensitized but clinically tolerant and in 4 the double blind placebo-controlled food challenge (DBPCFC) is scheduled. To finalize the RCT we will apply for a cost-neutral prolongation of 1 year. We propose to follow-up cohort 1 for additional 12 months in the 2nd funding period, in which the children will continue their interventional product in a blinded manner independent of their sensitization or clinical reactivity as long as they tolerate it. We will then determine IgE-mediated FA to at least one of the four foods at two years of age. In addition, we will enroll 138 children (cohort 2) age 8 months to 4 years sensitized to HE, CM, PN and/or HN. These children will be randomized 1:1 receiving either 2 mg of the relevant allergen OR placebo on a daily basis for 3-6 months until the scheduled DBPCFC will be conducted. The primary endpoint will be IgE-mediated food allergy after intervention to any of the four foods. We hypothesize that the introduction and regular consumption of small amounts of food allergens at a later time point, even outside of the “window-of opportunity” is safe and will result in an increase of tolerance in sensitized children without known clinical relevance. Our results of the RCTs will provide important data for prevention recommendation. We will be able to show whether an early and continuous feeding of small amounts of food allergens is safe and promotes oral tolerance even in sensitized children. By the provision of biosamples (serum, PBMCs, saliva, stool and skin swaps) to the B-projects mechanistic insights are delivered within this clinical research unit to better characterize and predict FA and tolerance.

• DFG Programme: Clinical Research Units
• Subproject of: KFO 339: Food Allergy and Tolerance (Food@)
• Co-Investigator: Professorin Dr. Kirsten Beyer