Stepwise Heat-Denaturated Protein Introduction for Tolerance Induction in Food Allergy

NCT06380673 | Recruiting

• 1 other identifier: s68299
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 5

Brief Summary

This interventional study aims to validate an early heated protein introduction protocol in cow's milk allergic children who already developed tolerance towards extensively heated cow's milk, in order to speed up the development of complete cow's milk tolerance. Natural complete tolerance induction towards cow's milk takes several years of strict cow's milk avoidance with high risk of anaphylaxis by accidental cow's milk intake. By shortening the time towards complete tolerance, not only the quality of life of both children and parents ameliorates drastically, the time frame for potential anaphylactic reactions is also strongly reduced and can be considered as a preventive strategy to reduce allergic reactions too. Moreover, this strategy has proved efficient for hen's egg allergy. The main question this study wants to answer is whether a 12 months stepwise heated cow's milk introduction (either by gradual reduction of the cooking time or by the use of the Flemish Milk Ladder) in 20'-cooked cow's milk tolerant subjects, results in a larger proportion of complete cow's milk tolerant children after 12 months compared to natural tolerance induction (with 20' cooked milk introduction only).

Conditions

Food Allergy; Cow Milk Allergy

Outcome Measures

Primary Outcomes (1)

• Complete cow's milk tolerance after 12 months of stepwise heated cow's milk introduction

  We here want to test the hypothesis that a total period of 12 months stepwise heated cow's milk introduction (either by gradual reduction of the cooking time or by the use of the Flemish Milk Ladder) in 20'-cooked cow's milk tolerant subjects, results in a larger proportion of complete cow's milk tolerant children after 12 months compared to natural tolerance induction (with 20' cooked milk introduction only).

  12 months

Secondary Outcomes (6)

• Time to complete tolerance in all three arms

  12 months

• Quality of life in all three arms

  12 months

• Clinical reactions

  12 months

• Side effects

  12 months

• IL-10-producing cow's milk specific regulatory T and B cells

  Three times in 12 months

Study Arms (4)

Stepwise introduction using gradually shorter heating of cow's milk proteins

OTHER

Step 1: open introduction of 20' cooked cow's milk (at least 10 mL per portion, 2-3X a week) for 3 months. Step 2: open introduction of 15' cooked cow's milk (at least 10 mL per portion, 2-3X a week) for 3 months. Step 3: open introduction of 10' cooked cow's milk (at least 10 mL per portion, 2-3X a week) for 3 months. Step 4: open introduction of 5' cooked cow's milk (at least 10 mL per portion, 2-3X a week) for 3 months.

Other: Implementation of cow's milk in decreasingly heated forms

Stepwise introduction using the Flemish Milk Ladder

OTHER

The first 5 steps of the Flemish Milk Ladder (each containing a, b and c part) will be gradually introduced at home, each step for 21 days (2-3X a week during 3 consecutive weeks after which 3 days "rest"). We consider the 6th step the equivalent of tolerance induction so step 6 will be allowed once the OFC with uncooked milk is passed.

Other: Implementation of cow's milk in decreasingly heated forms

Control arm with introduction of 20' cooked cow's milk

OTHER

Step 1: open introduction of 20' cooked cow's milk (at least 10 mL per portion, 2-3X a week) for 12 months.

Other: Implementation of heated cow's milk

Healthy age-matched subjects

OTHER

For work package 2, 15 healthy age-matched subjects are included to compare immunological mechanisms with.

Other: No intervention

Interventions

Implementation of cow's milk in decreasingly heated forms OTHER

Implementation of cow's milk in decreasingly heated forms in cow's milk allergic subjects, tolerant to heated cow's milk, to assess the influence on tolerance induction.

Stepwise introduction using gradually shorter heating of cow's milk proteins; Stepwise introduction using the Flemish Milk Ladder

Implementation of heated cow's milk OTHER

Implementation of heated cow's milk in cow's milk allergic subjects, tolerant to heated cow's milk, to assess the influence on tolerance induction.

Control arm with introduction of 20' cooked cow's milk

No intervention OTHER

Healthy subjects undergo no intervention.

Healthy age-matched subjects

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Children (1-18y) had or have a clinical diagnosis of IgE mediated cow's milk allergy based on positive history as well as skin prick testing and/or specific IgE detection by CAPtest in an allergy clinic.
• Children are at least 12 months old before introduction of heated cow's milk is considered.
• Children did not suffer from grade 4 anaphylaxis due to cow's milk-ingestion at presentation.
• Children have specific IgE levels to Bos d 8 below 1.2 kU/mL and/or children passed 20' cooked cow's milk provocation test executed on clinical judgement.

You may not qualify if:

• Children had grade 4 anaphylaxis due to cow's milk ingestion.
• Children are younger than 12 months old at the moment of passing 20' cooked cow's milk OFC.
• Parents are not able or not willing to adhere to a specific cow's milk protein-containing diet on a regular basis at home.
• Multiple food allergy, not compatible with any of the choices in the Flemish Milk Ladder.
• Parents and/or children are not willing to give IC/assent.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (5)

Imelda Hospital Bonheiden

Bonheiden, Belgium

RECRUITING

AZ Sint-Jan

Bruges, Belgium

RECRUITING

AZ Maria Middelares

Ghent, Belgium

RECRUITING

Jessa Hospital

Hasselt, Belgium

RECRUITING

UZ Leuven Gasthuisberg

Leuven, Belgium

RECRUITING

MeSH Terms

Conditions

Food Hypersensitivity; Milk Hypersensitivity

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Jasmine Leus, MD

  Maria Middelares Hospital, Gent

  PRINCIPAL INVESTIGATOR

• Katrien Coppens, MD

  Imelda Hospital, Bonheiden

  PRINCIPAL INVESTIGATOR

• Sophie Verelst, MD

  KU Leuven and Jessa Hospital, Hasselt

  PRINCIPAL INVESTIGATOR

• Kate Sauer, MD

  AZ Sint-Jan AV

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Dominique MA Bullens, Prof. MD

CONTACT

+32016343801; dominique.bullens@kuleuven.be

Marleen Jannis

CONTACT

+32016343801; marleen.jannis@uzleuven.be

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinic Head in Pediatrics-Allergy at UZ Leuven, Head of the Allergy and Clinical Immunology Research group at KU Leuven (prof., dr.)

Study Record Dates

• First Submitted: March 19, 2024
• First Posted: April 24, 2024
• Study Start: April 22, 2024
• Primary Completion (Estimated): December 30, 2028
• Study Completion (Estimated): December 30, 2029
• Last Updated: May 16, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

BE (5)