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

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

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.

Study Overview

• Status: Completed
• Conditions: Allergic Conjunctivitis; Allergy;Food; Allergic Asthma; Allergy Milk; Allergy Skin
• Intervention / Treatment: Dietary supplement: hypoallergenic formulas

• Study Type: Observational
• Enrollment (Actual): 365

Contacts and Locations

Study Locations

• Italy
  • Naples, Italy, 80131
    • University of Naples Federico II

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 1 year (Child)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

Children who were consecutively observed at a FP office because the recent occurrence of signs and symptoms possibly related to IgE-mediated CMA were sent to our tertiary centre for paediatric allergy for possible inclusion in the study. Only subjects who met the inclusion criteria will be invited to participate to the study.Written informed consent will be obtained from the parents of each subject. Anamnestic, demographic, anthropometric and clinical data, as well as information on socio-demographic factors, family and living conditions, parental history of allergic diseases, maternal smoking during pregnancy, environmental tobacco smoke exposure, number of siblings, and pet ownership were obtained from the parents and recorded in a clinical database. For children with sure diagnosis of IgE-mediated CMA during a 3-year follow-up,3 visits every 12 months will be performed. Stool samples for metagenomics and metabolomics and blood sample for epigenetics studies will be collected.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

5

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Federico II University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2014
• Primary Completion (Actual): May 1, 2020
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: February 21, 2019
• First Submitted That Met QC Criteria: March 1, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): August 25, 2023
• Last Update Submitted That Met QC Criteria: August 23, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Hypersensitivity, Immediate; Eye Diseases; Conjunctival Diseases; Hypersensitivity; Milk Hypersensitivity; Conjunctivitis; Conjunctivitis, Allergic; Food Hypersensitivity
• Other Study ID Numbers: 109n19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No