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Epigenetic Effects Involved in Children With Cow's Milk Allergy (EPICMA)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02466035
Recruitment Status : Completed
First Posted : June 9, 2015
Last Update Posted : March 22, 2018
Information provided by (Responsible Party):
Roberto Berni Canani, Federico II University

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. The current study will prospectively evaluate the effect of Nutramigen LGG and other commercially available hypoallergenic formulas on epigenetic mechanisms that may be related to tolerance acquisition.

Condition or disease Intervention/treatment Phase
Cow's Milk Allergy Dietary Supplement: Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Atopic March of Lactobacillus GG (EPICMA)
Study Start Date : May 2014
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
Experimental: Lactobacillus GG
Treatment with Lactobacillus rhamnosus GG
Dietary Supplement: Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG

No Intervention: Other formula
Children assuming other hypoallergenic formulas

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

Information from the National Library of Medicine

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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02466035

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University of Naples Federico II
Naples, Italy, 80131
Sponsors and Collaborators
Federico II University

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Responsible Party: Roberto Berni Canani, MD, PhD, Federico II University Identifier: NCT02466035     History of Changes
Other Study ID Numbers: 2815
First Posted: June 9, 2015    Key Record Dates
Last Update Posted: March 22, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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Milk Hypersensitivity
Immune System Diseases
Food Hypersensitivity
Hypersensitivity, Immediate
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action