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History of Changes for Study: NCT04184700
Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas (EPICMA II)
Latest version (submitted November 29, 2019) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 November 29, 2019 None (earliest Version on record)
Comparison Format:

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Study NCT04184700
Submitted Date:  November 29, 2019 (v1)

Open or close this module Study Identification
Unique Protocol ID: 28n15
Brief Title: Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas (EPICMA II)
Official Title: Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Hypoallergenic Formulas
Secondary IDs:
Open or close this module Study Status
Record Verification: November 2019
Overall Status: Unknown status [Previously: Not yet recruiting]
Study Start: December 10, 2019
Primary Completion: December 31, 2020 [Anticipated]
Study Completion: December 31, 2021 [Anticipated]
First Submitted: November 29, 2019
First Submitted that
Met QC Criteria:
November 29, 2019
First Posted: December 3, 2019 [Actual]
Last Update Submitted that
Met QC Criteria:
November 29, 2019
Last Update Posted: December 3, 2019 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Federico II University
Responsible Party: Principal Investigator
Investigator: Roberto Berni Canani
Official Title: Associate professor
Affiliation: Federico II University
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module 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.
Detailed Description:
Open or close this module Conditions
Conditions: Cow Milk Allergy
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Not Applicable
Interventional Study Model: Parallel Assignment
Number of Arms: 4
Masking: Double (Investigator, Outcomes Assessor)
Allocation: Randomized
Enrollment: 72 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
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
Open or close this module 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
Open or close this module Eligibility
Minimum Age: 6 Months
Maximum Age: 12 Months
Sex: All
Gender Based:
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.
Open or close this module Contacts/Locations
Locations: Italy
Pediatric Office
Naples, Italy, 80100
Contact:Contact: Roberto Berni Canani, MD, Ph 00390817462680 berni@unina.it
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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