Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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.

Condition or disease Intervention/treatment Phase
Cow Milk Allergy Dietary Supplement: EHCF+LGG Not Applicable

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 72 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Epigenetic Effects Involved in Children With Cow's Milk Allergy: A Possible Effect of Hypoallergenic Formulas
Estimated Study Start Date : December 10, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Allergy

Arm Intervention/treatment
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




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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   6 Months to 12 Months   (Child)
Sexes Eligible for Study:   All
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.

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 ClinicalTrials.gov identifier (NCT number): NCT04184700


Locations
Layout table for location information
Italy
Pediatric Office
Naples, Italy, 80100
Contact: Roberto Berni Canani, MD, Ph    00390817462680    berni@unina.it   
Sponsors and Collaborators
Federico II University

Layout table for additonal information
Responsible Party: Roberto Berni Canani, Associate professor, Federico II University
ClinicalTrials.gov Identifier: NCT04184700    
Other Study ID Numbers: 28n15
First Posted: December 3, 2019    Key Record Dates
Last Update Posted: December 3, 2019
Last Verified: November 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypersensitivity
Milk Hypersensitivity
Immune System Diseases
Food Hypersensitivity
Hypersensitivity, Immediate