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Completed

NCT Number: NCT05960045

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

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.

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Key information

Conditions

Cow Milk Allergy Food Hypersensitivity Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Milk Hypersensitivity Tolerance

Age range

9 month–3 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Ain Shams University

Cairo, Egypt

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patients age between 9 months old till 3 years old.
  • Patients with symptoms that suggest mild to moderate non IgE mediated Cow Milk Allergy
  • 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.

Treatment and study plan

Direct Milk antigen reintroduction

Dietary Supplement

Direct milk antigen re-introduction milk according to ESPGHAN guidelines

Milk ladder

Dietary Supplement

B: Milk ladder according to the iMAP guideline which are 6 weeks of gradual reintroduction starting with baked milk not direct antigen

Primary outcomes

  1. Compare the frequency of tolerance to milk between the two groups

    Time frame: 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 outcomes

  1. Recording of overall percentage of milk tolerance after 6 months elimination diet

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Ain Shams University

Other

Registry information

Important dates

Study start
2024
Primary completion
2025
Study completion
2025
First posted
Jul 25, 2023
Registry last updated
May 7, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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