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

NCT04184700 | Completed

• 1 other identifier: 28n15
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Cow Milk Allergy

Outcome Measures

Primary Outcomes (1)

• Epigenetic modifications in cytokines genes

  TSDR demethylation (prop.) of FOXP3 in children with cow's milk allergy. The primary outcome was the time-averaged FoxP3 Treg-Specific-Demethylation-Region (TSDR) demethylation (prop.), which took into account three repeated measures (0,6,12 months).

  12 months

Secondary Outcomes (7)

• Epigenetic modifications in cytokines genes

  6 and 12 months

• Epigenetic modifications in cytokines genes

  6 and 12 months

• Epigenetic modifications in cytokines genes

  6 and 12 months

• microRNAs modifications

  12 months

• The rate of patients with immune tolerance acquisition to cow's milk protein

  12 months

Study Arms (5)

EHCF + LGG

EXPERIMENTAL

Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG

Dietary Supplement: EHCF+LGG

RHF

ACTIVE COMPARATOR

Extensively hydrolyzed rice formula

Dietary Supplement: RHF

EHWF

ACTIVE COMPARATOR

Extensively hydrolyzed protein formula

Dietary Supplement: EHWF

AAF

ACTIVE COMPARATOR

Amino acid based formula

Dietary Supplement: AAF

SF

ACTIVE COMPARATOR

Soy formula

Dietary Supplement: SF

Interventions

EHCF+LGG DIETARY_SUPPLEMENT

Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG

EHCF + LGG

RHF DIETARY_SUPPLEMENT

Rice hydrolysed formula

RHF

SF DIETARY_SUPPLEMENT

Soy formula

SF

EHWF DIETARY_SUPPLEMENT

extensively hydrolysed whey formula

EHWF

AAF DIETARY_SUPPLEMENT

amino acid based formula

AAF

Eligibility Criteria

• Age: 6 Months - 12 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• children with cow's milk allergy

You may not qualify if:

• 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,

Sponsors & Collaborators

• Federico II University: lead

Study Sites (1)

Pediatric Office

Naples, 80100, Italy

Location

MeSH Terms

Conditions

Milk Hypersensitivity

Condition Hierarchy (Ancestors)

Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full professor

Study Record Dates

• First Submitted: November 29, 2019
• First Posted: December 3, 2019
• Study Start: December 10, 2019
• Primary Completion: December 31, 2023
• Study Completion: August 31, 2024
• Last Updated: April 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)