Tolerance to Baked Goods in Allergic Children

NCT ID: NCT06998225

Last Updated: 2025-06-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

148 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-06-01

Study Completion Date

2019-12-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Food allergies are more common in children, especially in Western countries. Around 5 to 8% of children have at least one food allergy, compared to only 1-2% of adults. These allergies can really affect child's quality of life and create stress for the whole family. The most common foods that cause allergic reactions are cow's milk, egg, nuts, fish, and shellfish.

Until now, the usual way to manage a food allergy has been to completely avoid the food. But this can be hard, limiting kids diets and puts them at risk of accidental exposure, and may even cause nutritional problems.

Oral immunotherapy (OIT) has become and alternative treatment. It consists in giving very small amounts of the food allergen regularly to help the body get used to it. Some studies show this helps children build tolerance faster than just avoiding the food. But OIT also comes with risks, including allergic reactions during the treatment, some of which can be serious.

Some research is focusing on a gentler and safer option: giving children baked milk or baked egg. When milk or egg is baked (for example, in muffins or cookies), the high heat changes the proteins, making them less likely to cause allergic reactions. The heat breaks the parts of the protein that the immune system usually reacts to, and mixing them with wheat flour makes them even less reactive.

Interestingly, this doesn't work for every food, peanuts, for example, can actually become more allergenic when heated. But in the case of milk and egg, baking seems to be very helpful.

Giving baked milk or egg to allergic children has shown some immune system changes similar to OIT, but in a safer and more natural way. This can make life a lot easier, not just for the kids, but also for their families since it broadens their diet, improves their nutrition, and reduces stress in social situations.

Studies suggest that introducing baked milk and egg early on could also help kids become fully tolerant sooner.

At Sant Joan de Déu Hospital in Barcelona, doctors have been using OIT for milk and egg allergies since 2006 in children over 5 years old. While the treatment has helped many, not all children become fully desensitized, and some still react to milk or egg occasionally. The success rate is around 70%, and it's often less effective in children with severe allergies, like those who have had anaphylaxis.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

This is a 12-month, prospective, randomized interventional study designed to evaluate immunological tolerance development in young children with confirmed cow's milk or egg allergy. The primary endpoint is the acquisition of clinical tolerance to raw or minimally processed forms of the allergen after structured dietary exposure to baked forms. The study integrates immunologic, clinical, and laboratory evaluations to assess the therapeutic potential and immunomodulatory effects of gradual allergen introduction.

Study Population Inclusion Criteria Age: 12 to 72 months (1 to 6 years). Milk Allergy Subgroup: Confirmed diagnosis based on at least one of the following: suggestive clinical history, positive skin prick test (SPT) ≥3 mm over negative control and/or specific IgE ≥0.35 kU/L to cow's milk or casein.

Egg Allergy Subgroup: Either: suggestive clinical history and sensitization (SPT or sIgE ≥0.35 kU/L to egg white or ovomucoid).

Exclusion Criteria Inability to obtain written informed consent. Any contraindication to epinephrine use (e.g., uncorrected congenital heart disease).

Ongoing consumption of baked milk or egg ≥3 times/week within the last 3 months.

Baseline Procedures and Immune Profiling (T0)

All participants will undergo:

Supervised Oral Food Challenge (OFC) with a standardized baked milk or egg product (e.g., muffin containing measured protein quantity), carried out under hospital supervision with immediate access to emergency care.

Blood Sampling for:

Quantitative allergen-specific IgE, IgG4, IgA to milk/egg and their major components (e.g., casein, ovomucoid).

Flow cytometry for T-cell phenotyping (CD4⁺CD25⁺FoxP3⁺ regulatory T cells). Cytokine profiling via ELISA or multiplex immunoassay: IL-4, IL-5, IL-10, IL-13, TGF-β.

Basophil Activation Test (BAT) using CD63/CD203c expression upon allergen stimulation.

Skin Prick Testing with commercial milk/egg extracts and baked food extracts, if available.

Randomization and Treatment Arms

Participants are stratified based on baked food OFC outcome:

A. OFC-Positive to Baked Product

Randomized 1:1 to:

Baked Group 1 (Low-dose exposure): Daily ingestion of baked product containing fixed dose (e.g., 0.0375 g milk protein or 0.11 g egg protein).

Control Group 1 (Strict avoidance): Elimination of all milk/egg and derivatives.

Non-tolerant to minimum baked dose: Excluded from active intervention; followed as observational cohort with repeated testing at 12 months.

B. OFC-Negative to Baked Product Progress to OFC with pasteurized milk or cooked egg. If tolerant → study exit.

If reactive, randomization into:

Baked Group 2 (High-dose exposure): Daily ingestion of baked food containing higher protein load (e.g., 0.55 g milk protein or 1.1 g egg protein).

Control Group 2 (Strict avoidance).

All OFCs use a standardized 6-step titration protocol with cumulative dosing and observation for ≥2 hours post-ingestion.

Dose Escalation and Monitoring After 6 months: Hospital-based supervised dose escalation (doubling daily intake) for Baked Groups 1 and 2.

Final Assessment (T1 - 12 months) Repeat OFC with unheated (raw) milk or cooked/raw egg. Repeat blood testing, SPT, and BAT.

Comparative analysis between baseline and T1 to determine:

Acquisition of tolerance (negative OFC). Immune modulation (e.g., shifts in IgE/IgG4 ratios, Treg expansion, cytokine profile normalization).

Predictive value of baseline biomarkers for outcome stratification.

This detailed protocol structure enables reproducibility, comparability, and the possibility of identifying immunological biomarkers that correlate with successful oral immunotolerance induction through gradual dietary exposure to baked allergens.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Cow Milk Protein Allergy Hen Egg Allergy

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Dietary intervention with cow's milk or egg baked cookies low dose

Baked Group 1: consume a daily fixed low dose of baked milk (0.0375g of milk protein) or baked egg (0.11 g of egg protein).

Group Type ACTIVE_COMPARATOR

Dietary intervention using cookies containing milk or egg low dose.

Intervention Type DIETARY_SUPPLEMENT

Baked Group 1: consumed a daily fixed low dose of baked milk or egg (0.0375 g of milk protein or 0.11 g of egg protein) for 6 months, followed by an additional increase at that time (0.075 g or 0.22 g).

Cow's milk or egg allergy control low dose

Control Group 1: strict avoidance diet, excluding all milk or egg (as appropriate) and any foods containing them.

Group Type NO_INTERVENTION

No interventions assigned to this group

Dietary intervention with cow's milk or egg baked cookies high dose

Baked Group 2: continue a daily high dose of baked milk (0.55 g of milk protein) or baked egg (1.1 g of egg protein).

Group Type ACTIVE_COMPARATOR

Dietary intervention with cow's milk or egg baked cookies high dose

Intervention Type DIETARY_SUPPLEMENT

Baked Group 2: continued a daily high dose of baked milk (0.55 g of milk protein or 1.1g egg protein) for 6 months. An increase dose is given at that time (1.1g cow's milk or 2g egg protein).

Tolerance to baked cow's milk or egg.

Avoidance

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Dietary intervention using cookies containing milk or egg low dose.

Baked Group 1: consumed a daily fixed low dose of baked milk or egg (0.0375 g of milk protein or 0.11 g of egg protein) for 6 months, followed by an additional increase at that time (0.075 g or 0.22 g).

Intervention Type DIETARY_SUPPLEMENT

Dietary intervention with cow's milk or egg baked cookies high dose

Baked Group 2: continued a daily high dose of baked milk (0.55 g of milk protein or 1.1g egg protein) for 6 months. An increase dose is given at that time (1.1g cow's milk or 2g egg protein).

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Children with confirmed allergy to cow's milk or cooked egg

Exclusion Criteria

* Contraindication to epinephrine use
* Ongoing consumption of baked milk or egg goods
Minimum Eligible Age

12 Months

Maximum Eligible Age

6 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Hospital Sant Joan de Deu

OTHER

Sponsor Role collaborator

Fundació Sant Joan de Déu

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Montserrat Alvaro, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Hospital Sant Joan de Deu

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Barcelona

Esplugues de Llobregat, Barcelona, Spain

Site Status

Countries

Review the countries where the study has at least one active or historical site.

Spain

References

Explore related publications, articles, or registry entries linked to this study.

Muraro A, Roberts G, Clark A, Eigenmann PA, Halken S, Lack G, Moneret-Vautrin A, Niggemann B, Rance F; EAACI Task Force on Anaphylaxis in Children. The management of anaphylaxis in childhood: position paper of the European academy of allergology and clinical immunology. Allergy. 2007 Aug;62(8):857-71. doi: 10.1111/j.1398-9995.2007.01421.x. Epub 2007 Jun 21.

Reference Type RESULT
PMID: 17590200 (View on PubMed)

Leonard SA, Caubet JC, Kim JS, Groetch M, Nowak-Wegrzyn A. Baked milk- and egg-containing diet in the management of milk and egg allergy. J Allergy Clin Immunol Pract. 2015 Jan-Feb;3(1):13-23; quiz 24. doi: 10.1016/j.jaip.2014.10.001.

Reference Type RESULT
PMID: 25577613 (View on PubMed)

Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA. Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol. 2011 Jul;128(1):125-131.e2. doi: 10.1016/j.jaci.2011.04.036. Epub 2011 May 23.

Reference Type RESULT
PMID: 21601913 (View on PubMed)

Lambert R, Grimshaw KEC, Ellis B, Jaitly J, Roberts G. Evidence that eating baked egg or milk influences egg or milk allergy resolution: a systematic review. Clin Exp Allergy. 2017 Jun;47(6):829-837. doi: 10.1111/cea.12940. Epub 2017 May 17.

Reference Type RESULT
PMID: 28516451 (View on PubMed)

Anagnostou A, Mack DP, Johannes S, Shaker M, Abrams EM, DeSanto K, Greenhawt M. The Safety and Efficacy of Baked Egg and Milk Dietary Advancement Therapy: A Systematic Review and Meta-Analysis. J Allergy Clin Immunol Pract. 2024 Sep;12(9):2468-2480. doi: 10.1016/j.jaip.2024.06.016. Epub 2024 Jun 18.

Reference Type RESULT
PMID: 38901613 (View on PubMed)

Warren CM, Jiang J, Gupta RS. Epidemiology and Burden of Food Allergy. Curr Allergy Asthma Rep. 2020 Feb 14;20(2):6. doi: 10.1007/s11882-020-0898-7.

Reference Type RESULT
PMID: 32067114 (View on PubMed)

Provided Documents

Download supplemental materials such as informed consent forms, study protocols, or participant manuals.

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PIC-104-14

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.