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

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ClinicalTrials.gov Identifier: NCT02466035
Recruitment Status : Completed
First Posted : June 9, 2015
Last Update Posted : March 22, 2018
Sponsor:
Information provided by (Responsible Party):
Roberto Berni Canani, Federico II University

Tracking Information
First Submitted Date  ICMJE May 27, 2015
First Posted Date  ICMJE June 9, 2015
Last Update Posted Date March 22, 2018
Study Start Date  ICMJE May 2014
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 29, 2016)
  • 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
  • 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
Original Primary Outcome Measures  ICMJE
 (submitted: June 8, 2015)
Epigenetic modifications in cytokines genes [ Time Frame: 12 months ]
SErum levels and methylation rate of interleukin 4, interleukin 5, interleukin 10, interferon gamma in children with cow's milk allergy
Change History Complete list of historical versions of study NCT02466035 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2017)
microRNAs modifications [ Time Frame: 12 months ]
Expression of miR106a, miR126, miR21, miR145, miR27a, miR29a/b, miR155, miR146a, miR128
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epigenetic Effects Involved in Children With Cow's Milk Allergy (EPICMA)
Official Title  ICMJE Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Atopic March of Lactobacillus GG (EPICMA)
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Cow's Milk Allergy
Intervention  ICMJE Dietary Supplement: Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Extensively hydrolyzed casein formula containing the probiotic Lactobacillus rhamnosus GG
Study Arms  ICMJE
  • Experimental: Lactobacillus GG
    Treatment with Lactobacillus rhamnosus GG
    Intervention: Dietary Supplement: Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
  • No Intervention: Other formula
    Children assuming other hypoallergenic formulas
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 8, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2017
Actual Primary Completion Date December 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months to 12 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02466035
Other Study ID Numbers  ICMJE 2815
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Roberto Berni Canani, Federico II University
Study Sponsor  ICMJE Federico II University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Federico II University
Verification Date March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP