Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas (EPICMA II)

• ClinicalTrials.gov Identifier: NCT04184700
• Recruitment Status: Not yet recruiting
• First Posted: December 3, 2019
• Last Update Posted: December 3, 2019
• Sponsor: Federico II University
• Information provided by (Responsible Party): Roberto Berni Canani, Federico II University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cow Milk Allergy	Dietary Supplement: EHCF+LGG	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 72 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Hypoallergenic Formulas
• Estimated Study Start Date: December 10, 2019
• Estimated Primary Completion Date: December 31, 2020
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
Experimental: EHCF + LGG; Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG	Dietary Supplement: EHCF+LGG; Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
Active Comparator: RHF; Extensively hydrolyzed rice formula	Dietary Supplement: EHCF+LGG; Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
Active Comparator: EHWF; Extensively hydrolyzed protein formula	Dietary Supplement: EHCF+LGG; Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
Active Comparator: AAF; Amino acid based formula	Dietary Supplement: EHCF+LGG; Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG

Outcome Measures

Primary Outcome Measures :

1. Epigenetic modifications in cytokines genes [ Time Frame: 12 months ]
   Serum levels (pg/ml) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy
2. Epigenetic modifications in cytokines genes [ Time Frame: 12 months ]
   Methylation rate (%) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy

Secondary Outcome Measures :

1. microRNAs modifications [ Time Frame: 12 months ]
   Expression of miR106a, miR126, miR21, miR145, miR27a, miR29a/b, miR155, miR146a, miR128

Eligibility Criteria

• Ages Eligible for Study: 6 Months to 12 Months (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Italy

Pediatric Office

Naples, Italy, 80100

Contact: Roberto Berni Canani, MD, Ph 00390817462680 berni@unina.it

Sponsors and Collaborators

Federico II University

More Information

• Responsible Party: Roberto Berni Canani, Associate professor, Federico II University
• ClinicalTrials.gov Identifier: NCT04184700
• Other Study ID Numbers: 28n15
• First Posted: December 3, 2019
• Last Update Posted: December 3, 2019
• Last Verified: November 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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