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

NCT05960045 | Completed

• 1 other identifier: MS 476/2021
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

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.

Conditions

Cow Milk Allergy; Tolerance

Outcome Measures

Primary Outcomes (1)

• Compare the frequency of tolerance to milk between the two groups

  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

  intervention will be made six months of elimination diet, and follow up of 2 months later

Secondary Outcomes (1)

• 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

Study Arms (2)

Patients receiving direct milk antigen (Group A)

ACTIVE COMPARATOR

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

Dietary Supplement: Direct Milk antigen reintroduction

Patients subjected to gradual reintroduction of milk through a milk ladder (Group B)

ACTIVE COMPARATOR

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.

Dietary Supplement: Milk ladder

Interventions

Direct Milk antigen reintroduction DIETARY_SUPPLEMENT

Direct milk antigen re-introduction milk according to ESPGHAN guidelines

Patients receiving direct milk antigen (Group A)

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

Patients subjected to gradual reintroduction of milk through a milk ladder (Group B)

Eligibility Criteria

• Age: 9 Months - 3 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Ain Shams University: lead

Study Sites (1)

Ain Shams University

Cairo, Egypt

Location

Related Publications (15)

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  PMID: 12487206 BACKGROUND

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  PMID: 30027590 BACKGROUND

• Fiocchi A, Schunemann HJ, Brozek J, Restani P, Beyer K, Troncone R, Martelli A, Terracciano L, Bahna SL, Rance F, Ebisawa M, Heine RG, Assa'ad A, Sampson H, Verduci E, Bouygue GR, Baena-Cagnani C, Canonica W, Lockey RF. Diagnosis and Rationale for Action Against Cow's Milk Allergy (DRACMA): a summary report. J Allergy Clin Immunol. 2010 Dec;126(6):1119-28.e12. doi: 10.1016/j.jaci.2010.10.011.

  PMID: 21134569 BACKGROUND

• Kim JS, Nowak-Wegrzyn A, Sicherer SH, Noone S, Moshier EL, Sampson HA. Dietary baked milk accelerates the resolution of cow's milk allergy in children. J Allergy Clin Immunol. 2011 Jul;128(1):125-131.e2. doi: 10.1016/j.jaci.2011.04.036. Epub 2011 May 23.

  PMID: 21601913 BACKGROUND

• Koletzko S, Niggemann B, Arato A, Dias JA, Heuschkel R, Husby S, Mearin ML, Papadopoulou A, Ruemmele FM, Staiano A, Schappi MG, Vandenplas Y; European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Diagnostic approach and management of cow's-milk protein allergy in infants and children: ESPGHAN GI Committee practical guidelines. J Pediatr Gastroenterol Nutr. 2012 Aug;55(2):221-9. doi: 10.1097/MPG.0b013e31825c9482.

  PMID: 22569527 BACKGROUND

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  PMID: 28516451 BACKGROUND

• Longo G, Barbi E, Berti I, Meneghetti R, Pittalis A, Ronfani L, Ventura A. Specific oral tolerance induction in children with very severe cow's milk-induced reactions. J Allergy Clin Immunol. 2008 Feb;121(2):343-7. doi: 10.1016/j.jaci.2007.10.029. Epub 2007 Dec 26.

  PMID: 18158176 BACKGROUND

• Luyt D, Ball H, Makwana N, Green MR, Bravin K, Nasser SM, Clark AT; Standards of Care Committee (SOCC) of the British Society for Allergy and Clinical Immunology (BSACI). BSACI guideline for the diagnosis and management of cow's milk allergy. Clin Exp Allergy. 2014;44(5):642-72. doi: 10.1111/cea.12302.

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• Venter C, Brown T, Meyer R, Walsh J, Shah N, Nowak-Wegrzyn A, Chen TX, Fleischer DM, Heine RG, Levin M, Vieira MC, Fox AT. Better recognition, diagnosis and management of non-IgE-mediated cow's milk allergy in infancy: iMAP-an international interpretation of the MAP (Milk Allergy in Primary Care) guideline. Clin Transl Allergy. 2017 Aug 23;7:26. doi: 10.1186/s13601-017-0162-y. eCollection 2017.

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• Yang M, Tan M, Wu J, Chen Z, Long X, Zeng Y, Cai H, Zhang Y, Geng L, Xiao Y, Ke H, Liu Y, Rong L, Fu S, Wang H, Wang Y, Li X, Chen P, Li K, Xie J, Chen H, Li H, Wang H, Li DY, Gong S. Prevalence, Characteristics, and Outcome of Cow's Milk Protein Allergy in Chinese Infants: A Population-Based Survey. JPEN J Parenter Enteral Nutr. 2019 Aug;43(6):803-808. doi: 10.1002/jpen.1472. Epub 2018 Nov 19.

  PMID: 30452099 BACKGROUND

MeSH Terms

Conditions

Milk Hypersensitivity

Condition Hierarchy (Ancestors)

Food Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Ahmed Saber

  AinShams University

  STUDY DIRECTOR

• Yasmine El-Gendy

  AinShams university

  STUDY DIRECTOR

• Yosra Awad

  Ain Shams University

  STUDY DIRECTOR

• Nesreen Hammad

  Ain Shams University

  STUDY DIRECTOR

• Mostafa EL-Hodhod

  Ain Shams University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 2 groups

Study Record Dates

• First Submitted: September 10, 2022
• First Posted: July 25, 2023
• Study Start: July 1, 2024
• Primary Completion: April 15, 2025
• Study Completion: April 28, 2025
• Last Updated: May 7, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)