Epigenetic Effects Elicited By Lactobacillus GG In Children With Cow's Milk Allergy

NCT ID: NCT02062476

Last Updated: 2014-02-13

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-07-31

Brief Summary

Lactobacillus GG (LGG) is able to exert long lasting effects in children with atopic disorders. We have shown that Nutramigen LGG accelerates tolerance acquisition in infants with cow's milk allergy (CMA). 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 CMA (i.e., IL-4, IL-5, IL-10, IFN-γ , TGF-beta, and TNF-alfa), which can contribute to modulation of inflammatory processes. We 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 miRNA (miR-21) that is critical for the regulation of Th cell polarization.

Conditions

Cow's Milk Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment with Lactobacillus GG

extensively hydrolyzed casein formula containing LGG

Group Type: EXPERIMENTAL

Lactobacillus GG

Intervention Type: DIETARY_SUPPLEMENT

Children at diagnosis

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Lactobacillus GG

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• Children aged 4 months-4 years with cow's milk allergy

Exclusion Criteria

• age higher than 4 years,
• 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.

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 48 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federico II University

OTHER

Sponsor Role: lead

Responsible Party

Roberto Berni Canani

MD, PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

University of Naples Federico II

Naples, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Roberto Berni Canani, MD, PhD

Role: CONTACT

0817462680

Facility Contacts

Roberto Berni Canani

Role: primary

0817462680

Other Identifiers

1/14

Identifier Type: -

Identifier Source: org_study_id