Testing Tolerance in Cow Milk Protein Allergy Patients: Milk Ladder or Direct Milk Administration?

Not Applicable

Completed

• Conditions: Tolerance; Cow Milk Allergy
• Interventions: Dietary Supplement: Direct Milk antigen reintroduction; Dietary Supplement: Milk ladder

• Registration Number: NCT05960045
• Lead Sponsor: Ain Shams University

Brief Summary

Majority of children outgrow their allergies, however there are two different methods to re-introduce milk products in the infant diet either direct milk intake in escalating doses or milk ladder, starting with baked milk products instead of pure milk.

This study aims to compare rate of tolerance after milk reintroduction among patient with cow milk protein allergy (CMPA) diagnosed by elimination re-challenge test after six months of elimination diet by milk ladder versus direct milk intake.

Detailed Description

CMPA is an immunological response to one or more milk proteins. CMPA may be IgE mediated or Non-IgE mediated. It is one of the most frequent causes of food allergies in young children with an estimated prevalence between 1.9% and 4.9% in the first year of life.

CMPA has a good prognosis and cow milk is reintroduced in child diet. Natural history of CMPA shows heterogeneity and it is closely related to the clinical phenotype by which it was presented.

The timing and evaluation of developing tolerance is determined by clinical response to milk introduction.

When diagnosis of CMPA is confirmed, fresh pasteurized cow's milk can be used above 12 months of age in oral food challenge procedure, the starting dose should be lower than a dose that can induce a reaction and then increased step wise to 100ml, in children with mild to moderate reactions doses of 1ml, 3ml, 10ml, 30ml, and 100ml may be given at 30 minutes' intervals.

The milk ladder is an evidence-based plan to re-introduce milk products gradually and in stages for infants and children with mild to moderate cow's milk allergy, starting with food that contain only small amount of well-cooked milk and progressing towards uncooked dairy products and fresh milk. It's only started once child has been on a milk free diet for at least 6 months and they are completely well with no active eczema or gastro-intestinal symptoms.

Addition of baked- milk to the diet appears to accelerate the development of unheated-milk tolerance compared to strict avoidance, also its consumption is considered a form of immunotherapy with favorable safety, higher convenience, lower cost and less intensity when compared to oral immunotherapy. It's suggested to enhance the quality of life by removing unnecessary dietary restrictions and change the natural evaluation of milk allergy by promoting the development of tolerance to regular cow's milk.

Study Timeline

• Study First Submitted: 2022-09-10
• Study First Submitted QC: 2023-07-21
• Study First Posted: 2023-07-25
• Study Start: 2024-07-01
• Status Verified: 2025-04
• Primary Completion: 2025-04-15
• Study Completion: 2025-04-28
• Last Update Submitted: 2025-05-06
• Last Update Posted: 2025-05-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 116

Inclusion Criteria

1. Patients age between 9 months old till 3 years old.
2. Patients with symptoms that suggest mild to moderate non IgE mediated Cow Milk Allergy
3. Patients on strict elimination diet for at least six months duration

Exclusion Criteria

Patient with:

• Chronic gastrointestinal disease (malabsorption, irritable bowel syndrome).
• Multiple food allergy and/or history of anaphylaxis.
• Ongoing eczema or severe gastrointestinal symptoms.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Patients receiving direct milk antigen (Group A)	Direct Milk antigen reintroduction	Patients with cow milk protein allergy after 6 month of elimination diet will receive direct milk antigen and will be followed up for 2 months for the development of any symptoms of milk intolerance
Patients subjected to gradual reintroduction of milk through a milk ladder (Group B)	Milk ladder	Patient with cow milk protein allergy after 6 month of elimination diet will be offered indirect milk antigen through a ladder starting by baked milk products and will be followed up for also for 2 months to detect any symptoms of intolerance.

Primary Outcome Measures

Name	Time	Method
Compare the frequency of tolerance to milk between the two groups	intervention will be made six months of elimination diet, and follow up of 2 months later	Questionnaire done to assess occurrence of following symptoms Vomiting, Hematemesis, Diarrhea (using BRISTOL scale), Constipation, Eczema, Skin rash, Perianal inflammation, weight loss in kilograms or failure to gain weight in kilograms, (Colic, Straining and marked Abdominal distension), and recurrent respiratory symptoms within two months of following up after milk reintroduction. If any of the previous items is present, then the patient is considered intolerant to milk. All items should be answered by (no) in order to consider the patient tolerant to milk

Secondary Outcome Measures

Name	Time	Method
Recording of overall percentage of milk tolerance after 6 months elimination diet	intervention will be made six months of elimination diet, and follow up of 2 months later	the same questionnaire used to assess tolerance to milk products. Also all answers should be answered by No, otherwise patient would still be considered intolerant.

Trial Locations

Locations (1)

Ain Shams University; 🇪🇬 Cairo, Egypt