Cow's Milk AllergyNCT02779881
Epigenetic Features of FoxP3 in Children With Cow's Milk Allergy
An observational study of Cow's Milk Allergy, run by Federico II University at 1 site in Italy.
Trial summary
Epigenetic mechanisms have been implicated in the pathogenesis of food allergy. The investigators previously demonstrated that tolerance acquisition in children with Immunoglobulin E- (IgE) mediated cow's milk allergy (CMA) is driven by epigenetic modulation of the Th1 and Th2 cytokine genes. Read more about this study
- Who is it for?
- Ages 3 to 18 months
- Conditions the study is for
- Cow's Milk Allergy
- What is being tested?
- Extensively hydrolyzed casein formula plus LGG
- How many people
- 40 participants
- Where
- 1 siteItaly
- Study dates
- Dec 2012to Apr 2014
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 3 to 18 months
- All sexes
- No healthy volunteers
- Child
Study population: IgE-mediated CMA children (aged 3 to 18 months) consecutively referred to the tertiary Pediatric Allergy Center for oral food challenge. During the same study period, consecutive healthy children, not at risk of atopic disorders (namely, those without a first-degree relative affected by an atopic disorder), attending the Center because of minimal surgical procedures served as a control group. A venous blood sample (4 ml) was obtained from all patients after oral challenge.
Who may be able to join
- IgE-mediated CMA children (aged 3 to 18 months)
Who cannot join
- allergic disorders or food allergies other than cow's milk allergy
- eosinophilic disorders of the gastrointestinal tract
- food protein-induced enterocolitis syndrome
- concomitant chronic systemic diseases
- congenital cardiac defects
- active tuberculosis
Show all 16Show fewer
- autoimmune diseases
- immunodeficiency
- chronic inflammatory bowel diseases
- celiac disease
- cystic fibrosis
- metabolic diseases
- lactose intolerance
- malignancy
- chronic pulmonary diseases
- malformations of the gastrointestinal tract
Trial locations and contacts
1 site in 1 country.
About this study
Epigenetic mechanisms have been implicated in the pathogenesis of food allergy. The investigators previously demonstrated that tolerance acquisition in children with Immunoglobulin E- (IgE) mediated cow's milk allergy (CMA) is driven by epigenetic modulation of the Th1 and Th2 cytokine genes. A regulatory T cell (Treg) suppressive phenotype, characterized by stable expression of the transcription factor "Forkhead box Protein 3" (FoxP3), plays a pivotal role in food tolerance. FoxP3 mRNA expression is lower in children with atopic asthma or IgE-mediated food allergy than in healthy children. FoxP3 stable expression requires full CpG demethylation of its transcriptional regulatory regions, and, moreover, hypermethylation of the FoxP3 gene has been associated with reduced Treg function and allergy.
DNA methylation is a biologically and chemically stable epigenetic modification that locks in long-term gene expression patterns. The demethylation status of FoxP3 at a highly conserved region within the Treg-specific-demethylated-region (TSDR), a CpG-rich, located on the 2nd conserved non-coding sequence of FoxP3 (CNS2), is restricted to Tregs. Transcriptional activity of the TSDR is essentially determined by its methylation status : it is completely inactive in its methylated state, but when the TSDR is demethylated, transcription factors such as Ets-1 and Creb can bind to the TSDR. TSDR demethylated and open chromatin conformation in the Foxp3 locus leads to stable phenotype differentiated Foxp3+ Treg. FoxP3 TSDR demethylation in peripheral blood mononuclear cells (PBMCs) has been associated with reduced atopic sensitization and asthma in children. Epigenetic regulation of antigen-induced T-cell subsets may predict a state of immune tolerance in food allergy. Indeed, DNA methylation of the FoxP3 gene in Tregs decreased during oral tolerance acquisition in patients with peanut allergy undergoing oral immunotherapy. The aim of this study was to evaluate further the epigenetic regulation of FoxP3 gene in children with IgE-mediated CMA.
- Conditions
- Cow's Milk Allergy
- Being tested
- Extensively hydrolyzed casein formula plus LGG
- Medical subject headings
- Milk Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Extensively hydrolyzed casein formula plus LGGDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| Healthy controls | Healthy controls | |
| Children at diagnosis of cow's milk allergy | Children at diagnosis of cow's milk allergy | |
| Subjects outgrown cow's milk allergy with formula+probiotic | Tolerant with extensively hydrolyzed casein formula with Lactobacillus rhamnosus GG Receives: Dietary Supplement: Extensively hydrolyzed casein formula plus LGG | |
| Subjects outgrown cow's milk allergy assuming other formulas | Subjects tolerant with other formulas |
What is being measured
The primary outcome is the main question the study is designed to answer.
DNA demethylation (rate, in %) of the Treg-specific-demethylated-region (TSDR) of FoxP3
Measured: At enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2016 (estimated)
- Study startDec 2012
- Primary completionApr 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cow's Milk AllergyStudies of the same condition, open and under way.
- More trials run by Federico II UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Federico II University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roberto Berni Canani, Federico II University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02779881
- Sponsor's protocol ID
- 1-14
- Status last verified
- May 2016
- First submitted
- 16 May 2016
- Last updated
- 23 May 2016
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Paparo L, Nocerino R, Cosenza L, Aitoro R, D'Argenio V, Del Monaco V, Di Scala C, Amoroso A, Di Costanzo M, Salvatore F, Berni Canani R. Epigenetic features of FoxP3 in children with cow's milk allergy. Clin Epigenetics. 2016 Aug 12;8:86. doi: 10.1186/s13148-016-0252-z. eCollection 2016.
PubMed 27525046
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Features of FoxP3 in Children With Cow's Milk Allergy
- ClinicalTrials.gov ID
- NCT02779881
- Acronym / sponsor ID
- 1-14
- Conditions
- Cow's Milk Allergy
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Federico II UniversityUniversity, hospital or other
- Study start
- Dec 2012
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 23 May 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Epigenetic mechanisms have been implicated in the pathogenesis of food allergy. The investigators previously demonstrated that tolerance acquisition in children with Immunoglobulin E- (IgE) mediated cow's milk allergy (CMA) is driven by epigenetic modulation of the Th1 and Th2 cytokine genes. A regulatory T cell (Treg) suppressive phenotype, characterized by stable expression of the transcription factor "Forkhead box Protein 3" (FoxP3), plays a pivotal role in food tolerance. FoxP3 mRNA expression is lower in children with atopic asthma or IgE-mediated food allergy than in healthy children. FoxP3 stable expression requires full CpG demethylation of its transcriptional regulatory regions, and, moreover, hypermethylation of the FoxP3 gene has been associated with reduced Treg function and allergy.
DNA methylation is a biologically and chemically stable epigenetic modification that locks in long-term gene expression patterns. The demethylation status of FoxP3 at a highly conserved region within the Treg-specific-demethylated-region (TSDR), a CpG-rich, located on the 2nd conserved non-coding sequence of FoxP3 (CNS2), is restricted to Tregs. Transcriptional activity of the TSDR is essentially determined by its methylation status : it is completely inactive in its methylated state, but when the TSDR is demethylated, transcription factors such as Ets-1 and Creb can bind to the TSDR. TSDR demethylated and open chromatin conformation in the Foxp3 locus leads to stable phenotype differentiated Foxp3+ Treg. FoxP3 TSDR demethylation in peripheral blood mononuclear cells (PBMCs) has been associated with reduced atopic sensitization and asthma in children. Epigenetic regulation of antigen-induced T-cell subsets may predict a state of immune tolerance in food allergy. Indeed, DNA methylation of the FoxP3 gene in Tregs decreased during oral tolerance acquisition in patients with peanut allergy undergoing oral immunotherapy. The aim of this study was to evaluate further the epigenetic regulation of FoxP3 gene in children with IgE-mediated CMA.
Study design
- Observational model
- Case crossover
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Healthy controls | – | –Healthy controls |
| Children at diagnosis of cow's milk allergy | – | –Children at diagnosis of cow's milk allergy |
| Subjects outgrown cow's milk allergy with formula+probiotic | – | Dietary Supplement: Extensively hydrolyzed casein formula plus LGGTolerant with extensively hydrolyzed casein formula with Lactobacillus rhamnosus GG |
| Subjects outgrown cow's milk allergy assuming other formulas | – | –Subjects tolerant with other formulas |
Who may qualify
- Ages
- 3 to 18 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
- Study population
- IgE-mediated CMA children (aged 3 to 18 months) consecutively referred to the tertiary Pediatric Allergy Center for oral food challenge. During the same study period, consecutive healthy children, not at risk of atopic disorders (namely, those without a first-degree relative affected by an atopic disorder), attending the Center because of minimal surgical procedures served as a control group. A venous blood sample (4 ml) was obtained from all patients after oral challenge.
Key inclusion criteria (1 listed)
- IgE-mediated CMA children (aged 3 to 18 months)
Key exclusion criteria (16 listed)
- allergic disorders or food allergies other than cow's milk allergy
- eosinophilic disorders of the gastrointestinal tract
- food protein-induced enterocolitis syndrome
- concomitant chronic systemic diseases
- congenital cardiac defects
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Extensively hydrolyzed casein formula plus LGG | Dietary supplement | Subjects outgrown cow's milk allergy with formula+probiotic |
Primary outcome
DNA demethylation (rate, in %) of the Treg-specific-demethylated-region (TSDR) of FoxP3
Time frame: At enrollment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2016.
- Derived from this study: PubMed 27525046Paparo L, Nocerino R, Cosenza L, Aitoro R, D'Argenio V, Del Monaco V, Di Scala C, Amoroso A, Di Costanzo M, Salvatore F, Berni Canani R. Epigenetic features of FoxP3 in children with cow's milk allergy. Clin Epigenetics. 2016 Aug 12;8:86. doi: 10.1186/s13148-016-0252-z. eCollection 2016.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cow's Milk Allergy, run by Federico II University at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
DNA demethylation (rate, in %) of the Treg-specific-demethylated-region (TSDR) of FoxP3 (time frame: At enrollment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02779881, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2016.