Clinical trial NCT06998225: Tolerance to Baked Goods in Allergic Children
Official title: Tolerance to Baked Goods in Children Under 5 Years Allergic to Cow's Milk or Egg Proteins
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cow Milk Protein Allergy
Hen Egg Allergy
Keywords: baked food tolerance
Lead sponsor: Fundació Sant Joan de Déu
Sponsor class: OTHER
Collaborators: name: Hospital Sant Joan de Deu
First posted: 2025-05-31
Enrollment: 148
Sex: ALL
Minimum age (years): 12
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 1. To evaluate proportion of children who develop tolerance to raw milk or cooked/raw egg at 12 months.
timeFrame: 12 months from enrollment
Secondary outcomes:
measure: Change in immunologic markers (IgE, IgG4, Tregs, BAT).
timeFrame: 12 months intervention
measure: Rate of reactions during oral food challenges.
timeFrame: 12 months intervention
measure: Changes in threshold dose triggering reactions.
timeFrame: 12 months intervention
Other outcomes:
Locations:
city: Esplugues de LLobregat
country: Spain
facility: Barcelona
state: Barcelona
Study officials:
affiliation: Hospital Sant Joan de Deu
name: Montserrat Alvaro, PhD, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: 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.