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

Primary Purpose

Cow's Milk Allergy

Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Sponsored by
Federico II University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cow's Milk Allergy

Eligibility Criteria

6 Months - 12 Months (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Naples Federico II

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

No Intervention

Arm Label

Lactobacillus GG

Other formula

Arm Description

Treatment with Lactobacillus rhamnosus GG

Children assuming other hypoallergenic formulas

Outcomes

Primary Outcome Measures

Epigenetic modifications in cytokines genes
Serum levels (pg/ml) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy
Epigenetic modifications in cytokines genes
Methylation rate (%) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy

Secondary Outcome Measures

microRNAs modifications
Expression of miR106a, miR126, miR21, miR145, miR27a, miR29a/b, miR155, miR146a, miR128

Full Information

First Posted
May 27, 2015
Last Updated
March 21, 2018
Sponsor
Federico II University
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1. Study Identification

Unique Protocol Identification Number
NCT02466035
Brief Title
Epigenetic Effects Involved in Children With Cow's Milk Allergy (EPICMA)
Official Title
Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Atopic March of Lactobacillus GG (EPICMA)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2018
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Federico II University

4. Oversight

5. 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. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cow's Milk Allergy

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lactobacillus GG
Arm Type
Experimental
Arm Description
Treatment with Lactobacillus rhamnosus GG
Arm Title
Other formula
Arm Type
No Intervention
Arm Description
Children assuming other hypoallergenic formulas
Intervention Type
Dietary Supplement
Intervention Name(s)
Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Intervention Description
Extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG
Primary Outcome Measure Information:
Title
Epigenetic modifications in cytokines genes
Description
Serum levels (pg/ml) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy
Time Frame
12 months
Title
Epigenetic modifications in cytokines genes
Description
Methylation rate (%) of interleukin 4, interleukin 5, interleukin 10, interferon gamma, FOXP3 in children with cow's milk allergy
Time Frame
12 months
Secondary Outcome Measure Information:
Title
microRNAs modifications
Description
Expression of miR106a, miR126, miR21, miR145, miR27a, miR29a/b, miR155, miR146a, miR128
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
12 Months
Accepts Healthy Volunteers
No
Eligibility 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.
Facility Information:
Facility Name
University of Naples Federico II
City
Naples
ZIP/Postal Code
80131
Country
Italy

12. IPD Sharing Statement

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

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