An interventional study of EHCF+LGG and RHF in Cow Milk Allergy, sponsored by Federico II University. Completed at 1 site in Italy. Open to participants aged 6 Months to 12 Months. Per ClinicalTrials.gov, last updated 2026-04-14.
Sponsored by Federico II University · Not applicable, Interventional, and Treatment
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.
147 studies on the registry are indexed under Milk Hypersensitivity; 26 are open to participants now.
This study's enrollment of 90 is above the median of 68 across 95 interventional studies indexed under Milk Hypersensitivity.
Browse Milk Hypersensitivity studies →Federico II University is the lead sponsor of 366 studies on the registry; 61 are open to participants now.
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Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Extensively hydrolyzed casein formula plus Lactobacillus rhamnosus GG
Dietary Supplement: EHCF+LGG
Extensively hydrolyzed rice formula
Dietary Supplement: RHF
Extensively hydrolyzed protein formula
Dietary Supplement: EHWF
Amino acid based formula
Dietary Supplement: AAF
Soy formula
Dietary Supplement: SF
Drug page: Lacticaseibacillus rhamnosus GG
Extensively hydrolyzed casein formula containing Lactobacillus rhamnosus GG
Rice hydrolysed formula
Soy formula
extensively hydrolysed whey formula
amino acid based formula
Epigenetic modifications in cytokines genes
TSDR demethylation (prop.) of FOXP3 in children with cow's milk allergy. The primary outcome was the time-averaged FoxP3 Treg-Specific-Demethylation-Region (TSDR) demethylation (prop.), which took into account three repeated measures (0,6,12 months).
Time frame: 12 months
Epigenetic modifications in cytokines genes
Demethtylation rate and expression (fc, fold change, ΔΔCt method)) of FOXP3 in children with cow's milk allergy
Time frame: 6 and 12 months
Epigenetic modifications in cytokines genes
Methylation rate (%) of interleukin IL-4, IL-5, IL-10, IFN-γ, in children with cow's milk allergy
Time frame: 6 and 12 months
Epigenetic modifications in cytokines genes
Serum levels (pg/ml) of interleukin IL-4, IL-5, IL-10, IFN-γ in children with cow's milk allergy
Time frame: 6 and 12 months
microRNAs modifications
Expression of miR-125b miR-146a miR-155 miR-29a/b miR-27a miR-128 miR-21 miR-126 miR-145 miR-106a miR-193a5p miR-128
Time frame: 12 months
The rate of patients with immune tolerance acquisition to cow's milk protein
Rate of patients with acquisition of tolerance to cow milk protein (rate of patients with outgrown cow's milk allergy)
Time frame: 12 months
Concentration of metagenomic characteristics of the intestinal microbiota
evaluation of composition of gut microbiota
Time frame: 12 months
Concentration of metabolomic characteristics of the intestinal microbiota
evaluation of function of gut microbiota
Time frame: 12 months
Plan to share: No
No publications or documents are linked to this record.
Ran from Dec 2019 to primary completion in Dec 2023, 48 months.
Of 34 interventional studies with no phase under Milk Hypersensitivity, half reached primary completion within 30 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 48. This study's 48 months is above that.
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This study is completed, as verified in Dec 2025. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Lacticaseibacillus rhamnosus GG