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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by Federico II University
Sponsor:
Information provided by (Responsible Party):
Roberto Berni Canani, Federico II University
ClinicalTrials.gov Identifier:
NCT02062476
First received: February 6, 2014
Last updated: February 12, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Cow's Milk Allergy
Dietary Supplement: Lactobacillus GG
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: EPIGENETIC EFFECTS ELICITED BY LACTOBACILLUS GG IN CHILDREN WITH COW'S MILK ALLERGY: A POSSIBLE EFFECT OF ATOPIC MARCH

Resource links provided by NLM:


Further study details as provided by Federico II University:

Primary Outcome Measures:
  • Change from baseline to 6 months in tolerance acquisition and epigenetic effects in rtwenty children with cow's milk allergy [ Time Frame: Baseline, at least after 6 months of therapy ] [ Designated as safety issue: No ]
    The investigators will evaluate in children with CMA if the effect of Lactobacillus GG on tolerance acquisition is mediated at least in part by an epigenetic mechanism.


Estimated Enrollment: 20
Study Start Date: July 2013
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment with Lactobacillus GG
extensively hydrolyzed casein formula containing LGG
Dietary Supplement: Lactobacillus GG
No Intervention: Children at diagnosis

  Eligibility

Ages Eligible for Study:   4 Months to 48 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02062476

Contacts
Contact: Roberto Berni Canani, MD, PhD 0817462680

Locations
Italy
University of Naples Federico II Recruiting
Naples, Italy, 80131
Contact: Roberto Berni Canani    0817462680      
Sponsors and Collaborators
Federico II University
  More Information

No publications provided

Responsible Party: Roberto Berni Canani, MD, PhD, Federico II University
ClinicalTrials.gov Identifier: NCT02062476     History of Changes
Other Study ID Numbers: 1/14
Study First Received: February 6, 2014
Last Updated: February 12, 2014
Health Authority: Italy: Ethics Committee

Additional relevant MeSH terms:
Hypersensitivity
Milk Hypersensitivity
Food Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases

ClinicalTrials.gov processed this record on November 20, 2014