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Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas (EPICMA II)

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04184700
Recruitment Status : Not yet recruiting
First Posted : December 3, 2019
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
Roberto Berni Canani, Federico II University

Tracking Information
First Submitted Date  ICMJE November 29, 2019
First Posted Date  ICMJE December 3, 2019
Last Update Posted Date December 3, 2019
Estimated Study Start Date  ICMJE December 10, 2019
Estimated Primary Completion Date December 31, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 29, 2019)
  • 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 Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: November 29, 2019)
microRNAs modifications [ Time Frame: 12 months ]
Expression of miR106a, miR126, miR21, miR145, miR27a, miR29a/b, miR155, miR146a, miR128
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Epigenetic Effects in Children With Cow's Milk Allergy Treated With Different Formulas
Official Title  ICMJE Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Hypoallergenic Formulas
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 Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Cow Milk Allergy
Intervention  ICMJE Dietary Supplement: EHCF+LGG
Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
Study Arms  ICMJE
  • Experimental: EHCF + LGG
    Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
    Intervention: Dietary Supplement: EHCF+LGG
  • Active Comparator: RHF
    Extensively hydrolyzed rice formula
    Intervention: Dietary Supplement: EHCF+LGG
  • Active Comparator: EHWF
    Extensively hydrolyzed protein formula
    Intervention: Dietary Supplement: EHCF+LGG
  • Active Comparator: AAF
    Amino acid based formula
    Intervention: Dietary Supplement: EHCF+LGG
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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: November 29, 2019)
72
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date December 31, 2020   (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
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04184700
Other Study ID Numbers  ICMJE 28n15
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
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 November 2019

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