Dietary Choice for the Management of Cow's Milk Allergy Influences Other Allergic Manifestations

Study Overview
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Brief Summary
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Food allergy is a common chronic condition in childhood. Recent studies have suggested that the natural history of food allergy has changed during the last two decades, with an increased prevalence, severity of clinical manifestations, and risk of persistence into later ages. The increased food allergy prevalence in children has an important economic impact, with significant direct costs for the healthcare system and even larger costs for the families of food-allergic patients. In addition, children with food allergies are at increased risk to develop other allergic manifestations later in life. According to a recent study, children with a food allergy are 2 to 4 times more likely to develop other atopic manifestations such as asthma (4.0 times), atopic eczema (2.4 times), and respiratory allergies (3.6 times), compared to children without a food allergy. Cow's milk allergy is among the most common food allergy in early childhood, with an estimated prevalence of 2% to 3%. It has been previously showed that in children with cow milk allergy, an extensively hydrolysed casein formula supplemented with the probiotic Lactobacillus rhamnosus GG induced higher tolerance rates compared to extensively hydrolysed casein formula without Lactobacillus rhamnosus GG and other formulas. These findings were consistent with those of a 1-year follow-up study performed in the US that showed better outcomes using an extensively hydrolysed casein formula+Lactobacillus rhamnosus GG vs. an extensively hydrolysed casein formula or amino acid-based formula for the first-line dietary management of cow milk allergy. In addition it has been recently demonstrated that extensively hydrolysed casein formula + Lactobacillus rhamnosus GG reduces the incidence of other atopic manifestations and hastens the development of oral tolerance in children with IgE-mediated cow milk allergy. The present randomized controlled trial (RCT) was designed to test whether different dietary interventions could influence the occurrence of other atopic manifestations in children with IgE-mediated cow milk allergy.

Official Title
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Dietary Choice for the Management of Cow's Milk Allergy Influences the Acquisition of Oral Tolerance and the Occurrence of Other Allergic Manifestations

Conditions
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Allergy Milk, Allergy;Food, Allergic Asthma, Allergic Conjunctivitis, Allergy Skin

Intervention / Treatment
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* Dietary Supplement: hypoallergenic formulas


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: age 1-12 months IgE-mediated CMA Exclusion Criteria: cow's milk protein-induced anaphylaxis, food protein induced enterocolitis syndrome, other food allergies, other allergic diseases, non-CMA-related atopic eczema, eosinophilic disorders of the gastrointestinal tract, chronic systemic diseases, congenital cardiac defects, active tuberculosis, autoimmune diseases, immunodeficiency, chronic inflammatory bowel diseases, celiac disease, cystic fibrosis, metabolic diseases, malignancy, chronic pulmonary diseases, malformations of the gastrointestinal and/or respiratory tract, administration of prebiotics or probiotics during the 4 weeks before enrolment.

Ages Eligible for Study
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Minimum Age: 1 Month
Maximum Age: 12 Months

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| extensively hydrolyzed casein formula+LGG<br>subjects with IgE mediated cow milk allergy treated with extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG as exclusion diet | Dietary Supplement: hypoallergenic formulas<br>* hypoallergenic formulas used for cow milk allergy treatment<br>|
| extensively hydrolyzed whey formula;<br>subjects with IgE mediated cow milk allergy treated with extensively hydrolyzed whey formula as exclusion diet | Dietary Supplement: hypoallergenic formulas<br>* hypoallergenic formulas used for cow milk allergy treatment<br>|
| hydrolyzed rice formula<br>subjects with IgE mediated cow milk allergy treated with hydrolyzed rice formula as exclusion diet | Dietary Supplement: hypoallergenic formulas<br>* hypoallergenic formulas used for cow milk allergy treatment<br>|
| soy based formula<br>subjects with IgE mediated cow milk allergy treated with soy based formula as exclusion diet | Dietary Supplement: hypoallergenic formulas<br>* hypoallergenic formulas used for cow milk allergy treatment<br>|
| amino-acid based formula<br>subjects with IgE mediated cow milk allergy treated with amino-acid based formula as exclusion diet | Dietary Supplement: hypoallergenic formulas<br>* hypoallergenic formulas used for cow milk allergy treatment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects with occurrence of other of allergic manifestations | To evaluate the effect of different dietary strategies on the occurrence of eczema, urticaria, asthma and rhinoconjunctivitis in children with IgE-mediated cow milk allergy | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of subjects with tolerance acquisition to cow's milk | To evaluate the tolerance acquisition to cow's milk | 3 years | 
| Change in metagenomics and metabolomics | 16S rRNA gene amplicon sequencing | 3 years | 
| Epigenetic modifications in cytokines genes | Serum levels (pg/ml) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy | 3 years | 
| Epigenetic modifications in cytokines genes | Methylation rate (%) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergyFOXP3 in children with cow's milk allergy | 3 years | 
| Rate of subjects with occurrence of other of allergic manifestations | To evaluate the effect of different dietary strategies on the occurrence of eczema, urticaria, asthma and rhinoconjunctivitis in children with IgE-mediated cow milk allergy | after 4 to 6 years follow-up | 
| Rate of subjects with tolerance acquisition to cow's milk | To evaluate the tolerance acquisition to cow's milk | after 4 to 6 years follow-up | 
| Rate of subjects with any autoimmune disease | To evaluate the occurrence of diabetes, celiac disease and thyroiditis | 6 years |