Effectiveness and Safety of Milk Ladders in Children with IgE-Mediated Cow's Milk Protein Allergy

NCT06664918 | Recruiting DMC

• 1 other identifier: ML2024
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 2

Brief Summary

Cow's milk protein allergy (CMPA) is one of the most common food allergies in early childhood. The first-line treatment of CMPA is the elimination of cow's milk proteins (CMPs) from the child's or maternal diet. Available data from the literature indicate that most children with CMPA acquire tolerance to CMPs with age. An assessment of tolerance acquisition to CMPs is commonly performed using milk ladder. However, scientific evidence regarding the effectiveness and safety of the milk ladder in children with CMPA is limited. Currently, there is no standardised milk ladder protocol, and different versions of the ladder and recommend by scientific societies in various countries. This study aims to assess the effectiveness and safety of the 4-step milk ladder (4-ML) compared to the 6-step milk ladder (6-ML) in children with IgE-mediated CMPA. This is an open-label, randomised superiority trial with two parallel arms and a 1:1 allocation ratio.

Conditions

Cow Milk Allergy; Food Allergy

Keywords

IgE-mediated cow's milk allergy; children; milk ladder

Outcome Measures

Primary Outcomes (1)

• The percentage of children who acquired tolerance to non-heated cow's milk proteins

  The percentage of children who acquired tolerance to non-heated cow's milk proteins defined as unreactive patients during OFC with non-heated cow's milk (the last step of milk ladder; a pasteurised cow milk or modified cow milk, the amount of 120-240 ml depending on the age of the patient, max. 7.95 g of CMPs)

  at the end of the observation period (12 or 20 weeks, depending on the study arm)

Secondary Outcomes (10)

• Percentage of children who experienced anaphylaxis

  during the observation period (12 or 20 weeks, depending on the study arm)

• Percentage of children who required adrenaline administration

  during the observation period (12 or 20 weeks, depending on the study arm)

• Change in BMI-for-age z-score

  at the end of the observation period (12 or 20 weeks, depending on the study arm) compared to baseline (before the first OFC)

• Assessment of parents' anxiety about adverse events during their child's OFC

  before each OFC, which means before the first OFC and depending on the study arm: after 4,8,12 weeks or after 4,8,12,16,20 weeks

• In a subgroup of children with atopic dermatitis, the percentage of children with mild, moderate, and severe atopic dermatitis

  before and after each OFC (during the examination following each observation period) which means before and after the first OFC and and before and after subsequent OFCs depending on the study arm: after 4,8,12 weeks or after 4,8,12,16,20 weeks

Study Arms (2)

4-step milk ladder

EXPERIMENTAL

Other: oral food challenge (OFC)

6-step milk ladder

ACTIVE COMPARATOR

Other: oral food challenge (OFC)

Interventions

oral food challenge (OFC) OTHER

oral food challenges with subsequent steps of 4-step milk ladder (muffin, pancake,baked hard cheese, yoghurt/pasteurised cow milk or modified cow milk)

4-step milk ladder

Eligibility Criteria

• Age: 1 Year - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age between 1 and 5 years.
• Diagnosis of IgE-mediated CMPA confirmed according to ESPGHAN guidelines, by a positive OFC with CMPs. In high-risk children (i.e., with a history of anaphylaxis), diagnosis based on positive skin prick testing and/or elevated specific IgE to CMPs is sufficient.
• On a therapeutic elimination diet for at least 6 months or up to 12 months of age.12
• Eligible regardless of the risk of systemic reaction (anaphylaxis) and asthma.
• Good overall health status.
• Parents without language barriers.
• Written informed consent signed by parents.
• Good cooperation with the child's guardians.

You may not qualify if:

• Uncontrolled asthma, defined as the presence of shortness of breath, chest tightness, cough, and/or auscultatory changes despite treatment.
• Signs of exacerbation of a chronic disease.
• Signs of acute infectious disease (i.e., acute runny nose, cough, subfebrile fever, or fever).
• Signs of exacerbation of another allergic disease (i.e., conjunctivitis, allergic rhinitis, atopic dermatitis).
• Anaphylaxis due to CMPs in the last 6 months.
• Used antihistamines within 3-10 days before the challenge (depending on the characteristics of the drug and the reason for use).
• Acquired tolerance to baked CMPs or higher steps of the milk ladder.
• Use of immunosuppressive drugs or immunotherapy

Sponsors & Collaborators

• Medical University of Warsaw: lead

Study Sites (2)

Medical University od Warsaw, Department od Pediatrics

Warsaw, Poland

RECRUITING

Medical University od Warsaw

Warsaw, Poland

NOT YET RECRUITING

Related Publications (1)

• Wiszniewska D, Horvath A, Strozyk A, Nowak-Wegrzyn A, Grzela K, Szajewska H. Effectiveness and safety of the four-step versus six-step milk ladder in children with IgE-mediated cow's milk protein allergy: protocol for an open-label randomised controlled trial. BMJ Open. 2025 Apr 14;15(4):e098314. doi: 10.1136/bmjopen-2024-098314.

  PMID: 40228856 DERIVED

MeSH Terms

Conditions

Milk Hypersensitivity; Food Hypersensitivity

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Andrea Horvath

  Medical University od Warsaw

  PRINCIPAL INVESTIGATOR

• Hanna Szajewska

  Medical University of Warsaw

  PRINCIPAL INVESTIGATOR

• Anna Nowak-Węgrzyn

  Collegium Medicum, University of Warmia and Mazury, Olsztyn, Poland; New York Univeristy, Grossmann School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrea Horvath, MD, PhD

CONTACT

048223179444; andrea.horvath@wum.edu.pl

Daria Wiszniewska, MD

CONTACT

048223179535; daria.wiszniewska@uckwum.pl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 16, 2024
• First Posted: October 30, 2024
• Study Start: December 3, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: March 18, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: After the publication of results, no later than 3 years from the completion of data analysis with no end date.
• Access Criteria: Upon reasonable request.

Locations

PL (2)