Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas

Cow Milk Allergy Clinical Trial

— EPICMA II  

Official title:

Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Hypoallergenic Formulas

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04184700
• Other study ID #: 28n15
• Status: Recruiting
• Phase: N/A
• Start date: December 10, 2019
• Est. completion date: August 31, 2024

Study information

• Verified date: February 2024
• Source: Federico II University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Lactobacillus GG (LGG) is able to exert long lasting effects in children with atopic disorders. Nutramigen LGG accelerates tolerance acquisition in infants with cow's milk allergy. The mechanisms of these effects are still largely undefined. The effect of LGG could be related at least in part by the immunoregulatory role played by LGG. This probiotic can balance the generation of cytokines possibly involved in IgE- or non-IgE-mediated cow's milk allergy Interleulkin (IL)-4, IL-5, IL-10, IFN-γ , TGF-β, and TNF-Υ), which can contribute to modulation of inflammatory processes. The investigators have demonstrated that children with IgE-mediated CMA produce significantly higher level of IL-4 and IL-13 in response to cow's milk protein, and that tolerance is associated with a marked reduction of IL-13 production and a concomitant increased frequency of IFN-γ releasing cells. Epigenetics studies the heritable (and potentially reversible) changes of the genome inherited from one cell generation to the next which alter gene expression but do not involve changes in primary DNA sequences, highlighting the complexity of the inter-relationship between genetics and nutrition. There are three distinct, but closely interacting, epigenetic mechanisms (histone acetylation, DNA methylation, and non-coding microRNAs) that are responsible for modifying the expression of critical genes associated with physiologic and pathologic processes. The profile of epigenetic modifications associated with Th lineage commitment, coupled with the sensitivity of the early developmental period, has led to speculation that factors that disrupt these pathways may increase the risk of allergic diseases. Specifically, effects on DNA methylation and endogenous histone deacetylase inhibitors acting on specific pathways (Th1 and T regulatory cell differentiation) may favour Th2-associated allergic differentiation. MicroRNAs are another structural components of an epigenetic mechanism of post-transcriptional regulation of messenger RNA translation. It has been recently identified a specific Th2-associated microRNA (miR-21) that is critical for the regulation of Th cell polarization. It has been previously demonstrated an inverse DNA methylation pattern of cytokines involved in Th2 response (IL-4, IL-5) compared with cytokines involved in Th1 response (IL-10, INF- y) in children with CMA acquiring oral tolerance, with the most pronounced effects in those treated with Nutramigen LGG.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 90
• Est. completion date: August 31, 2024
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 12 Months

Eligibility

Inclusion Criteria:

• children with cow's milk allergy

Exclusion Criteria:

• Concomitant 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 tract,
• suspected eosinophilic esophagitis or eosinophilic enterocolitis,
• suspected food-protein-induced enterocolitis syndrome,
• suspected cow's milk protein-induced anaphylaxis,
• still on exclusion diet with one of the study formulas or with another dietary regimen because of cow's milk allergy,
• other food allergies.

Related Conditions & MeSH terms

• Cow Milk Allergy
• Hypersensitivity
• Milk Hypersensitivity

Intervention

Dietary Supplement:
• EHCF+LGG
Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
• RHF
Rice hydrolysed formula
• SF
Soy formula
• EHWF
extensively hydrolysed whey formula
• AAF
amino acid based formula

Locations

Country	Name	City	State
Italy	Pediatric Office	Naples

Sponsors (1)

Lead Sponsor	Collaborator
Federico II University

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Epigenetic modifications in cytokines genes	Serum levels (pg/ml) of FOXP3 in children with cow's milk allergy	12 months
Primary	Epigenetic modifications in cytokines genes	Methylation rate (%) of FOXP3 in children with cow's milk allergy	12 months
Secondary	microRNAs modifications	Expression of miR-125b miR-146 miR-155 miR-29a/b miR-27 miR-128 let-7 family miR-21 miR-126 miR-145 miR-106a miR-375 miR-193a	12 months
Secondary	Concentration of metagenomic characteristics of the intestinal microbiota	evaluation of composition of gut microbiota	12 months
Secondary	Concentration of metabolomic characteristics of the intestinal microbiota	evaluation of function of gut microbiota	12 months
Secondary	The rate of patients with immune tolerance acquisition to cow's milk protein	Rate of patients with acquisition of tolerance to cow milk protein (rate of patients with outgrown cow's milk allergy)	12 months
Secondary	Epigenetic modifications in cytokines genes	Methylation rate (%) of interleukin IL-4, IL-5, IL-13, IL-10, IFN-?, FoxP3, GATA3, T-bet, TGF-ß, IL-17, IL-25, IL-12, IL-22, IL-6, IL-23 children with cow's milk allergy	6 and 12 months
Secondary	Epigenetic modifications in cytokines genes	Serum levels (pg/ml) of interleukin IL-4, IL-5, IL-13, IL-10, IFN-?, FoxP3, GATA3, T-bet, TGF-ß, IL-17, IL-25, IL-12, IL-22, IL-6, IL-23 in children with cow's milk allergy	6 and 12 months