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

Tolerance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05960045
• Other study ID #: MS 476/2021
• Status: Not yet recruiting
• Phase: N/A
• Start date: August 20, 2023
• Est. completion date: February 28, 2024

Study information

• Verified date: July 2023
• Source: Ain Shams University
• Contact: Nesreen Hammad
• Phone: 00201069628508
• Email: nesreenhammad637[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 116
• Est. completion date: February 28, 2024
• Est. primary completion date: February 15, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 9 Months to 3 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cow Milk Allergy
• Hypersensitivity
• Milk Hypersensitivity
• Tolerance

Intervention

Dietary Supplement:
• Direct Milk antigen reintroduction
Direct milk antigen re-introduction milk according to ESPGHAN guidelines
• Milk ladder
B: Milk ladder according to the iMAP guideline which are 6 weeks of gradual reintroduction starting with baked milk not direct antigen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Ain Shams University

References & Publications (15)

Bahna SL. Cow's milk allergy versus cow milk intolerance. Ann Allergy Asthma Immunol. 2002 Dec;89(6 Suppl 1):56-60. doi: 10.1016/s1081-1206(10)62124-2. — View Citation

Esmaeilzadeh H, Alyasin S, Haghighat M, Nabavizadeh H, Esmaeilzadeh E, Mosavat F. The effect of baked milk on accelerating unheated cow's milk tolerance: A control randomized clinical trial. Pediatr Allergy Immunol. 2018 Nov;29(7):747-753. doi: 10.1111/pa — View Citation

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 — View Citation

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. — View Citation

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 — View Citation

Lambert R, Grimshaw KEC, Ellis B, Jaitly J, Roberts G. Evidence that eating baked egg or milk influences egg or milk allergy resolution: a systematic review. Clin Exp Allergy. 2017 Jun;47(6):829-837. doi: 10.1111/cea.12940. Epub 2017 May 17. — View Citation

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 20 — View Citation

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 All — View Citation

NIAID-Sponsored Expert Panel; Boyce JA, Assa'ad A, Burks AW, Jones SM, Sampson HA, Wood RA, Plaut M, Cooper SF, Fenton MJ, Arshad SH, Bahna SL, Beck LA, Byrd-Bredbenner C, Camargo CA Jr, Eichenfield L, Furuta GT, Hanifin JM, Jones C, Kraft M, Levy BD, Lie — View Citation

Nicolaou N, Tsabouri S, Priftis KN. Reintroduction of cow's milk in milk-allergic children. Endocr Metab Immune Disord Drug Targets. 2014 Mar;14(1):54-62. doi: 10.2174/1871530314666140121150228. — View Citation

Niggemann B, Beyer K. Diagnosis of food allergy in children: toward a standardization of food challenge. J Pediatr Gastroenterol Nutr. 2007 Oct;45(4):399-404. doi: 10.1097/MPG.0b013e318054b0c3. — View Citation

Upton J, Nowak-Wegrzyn A. The Impact of Baked Egg and Baked Milk Diets on IgE- and Non-IgE-Mediated Allergy. Clin Rev Allergy Immunol. 2018 Oct;55(2):118-138. doi: 10.1007/s12016-018-8669-0. — View Citation

Vandenplas Y, Koletzko S, Isolauri E, Hill D, Oranje AP, Brueton M, Staiano A, Dupont C. Guidelines for the diagnosis and management of cow's milk protein allergy in infants. Arch Dis Child. 2007 Oct;92(10):902-8. doi: 10.1136/adc.2006.110999. Erratum In: — View Citation

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 — View Citation

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 — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Recording of overall percentage of milk tolerance after 6 months elimination diet	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.	intervention will be made six months of elimination diet, and follow up of 2 months later