Clinical trial NCT00778258: Study of Milk Allergy and Tolerance in Children
Official title: Dietary Intervention in Milk Allergy and Tolerance Development
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Food Hypersensitivity
Milk Hypersensitivity
Keywords: Food Allergy
Milk Allergy
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Asthma and Allergic Diseases Cooperative Research Centers
First posted: 2008-10-23
Enrollment: 170
Sex: ALL
Minimum age (years): 4
Maximum age (years): 10
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if children who are allergic to milk can increase tolerance through frequent dose-escalation every 6 months versus 12 months leading to eventual tolerance of less heated milk and ultimately unheated milk.

Detailed description: Milk is among the most common food allergens in infants and children. The majority of children outgrow their milk allergies; however, the exact mechanisms by which food tolerance is achieved are unknown. Strict avoidance of the offending food is currently the only known therapy. However, some have been known to tolerate milk products cooked at high heat such as when baked in foods.

This clinical trial involves a diet containing extensively baked milk protein to investigate the effects of ingestion of heat-denatured milk on development of oral tolerance to non-baked milk.

Eligibility criteria: Inclusion Criteria:

One or more of the following inclusion criteria for enrollment in the study have to be met:

* Convincing history of an allergic reaction to milk or a positive double blind placebo controlled milk challenge (DBPCMC) within the past 2 years and either detectable milk immunoglobulin E (IgE) or positive prick skin test to milk OR
* Serum milk-IgE of high predictive value \>14 kUa/L or prick skin test to milk \> 10mm wheal within the past 6 months regardless of past clinical history of reactions OR
* Convincing history of an allergic reaction to milk or a positive DBPCMC more than 2 years ago and either a positive serum milk-IgE \< 14 kUA/L or positive prick skin test to milk \< 10 mm wheal within the past 6 months (eligible only for the active arm of the study and will undergo a reversed sequence of initial baked-milk challenges)

Exclusion Criteria:

* Inability or unwillingness of a participant to give written informed consent or to comply with study protocol

Primary outcomes:
measure: Number of Participants With a Positive Progression in Tolerance of Baked Milk and Ultimately Unheated Milk in Dose Escalation Sub-arm Compared to Maintenance Sub-arm
timeFrame: Randomization through end of study (up to 36 months)
Secondary outcomes:
measure: Number of Participants With a Positive Progression in Tolerating More Allergenic Forms of Milk at 12 and 24 Months
timeFrame: 12 months, 24 months
measure: Percent of Participants Becoming Tolerant to Unheated Cow's Milk at 12, 24, and 36 Months
timeFrame: 12 months, 24 months, and 36 months
measure: Percent of Participants Becoming Tolerant to Unheated Cow's Milk
timeFrame: Randomization through end of study (up to 36 months)
measure: Comparison of Baseline Basophil Percent Maximal Degranulation With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
timeFrame: Baseline
measure: Comparison of Baseline IgE With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
timeFrame: Baseline
measure: Comparison of Baseline Mechanistic Studies [Treg and Basophil] With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity
timeFrame: Baseline
measure: Relationship Between Initial Dose of Tolerated Baked-milk Protein and Time to Complete Tolerance
timeFrame: Randomization through end of study (up to 36 months)
measure: Relationship Between Dose of Baked-milk Protein and Reactivity to Casein Versus Whey
timeFrame: Baseline, Month 12, Month 24, Month 36
measure: Comparison of Percent of Participants Tolerant to Non-heated Milk Between the Participants Who Ingested Baked-milk Products and Participants Who Continued to Avoid All Forms of Milk
timeFrame: Month 36
measure: Changes in Mechanistic Values [Humoral, T Cell and Basophil]
timeFrame: Baseline, Month 12, Month 24, and Month 36
measure: Changes in Mechanistic Values [Humoral, T Cell and Basophil]
timeFrame: Baseline to the time complete milk tolerance was established
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Hugh A. Sampson, MD
role: STUDY_CHAIR
affiliation: Icahn School of Medicine at Mount Sinai
name: Anna Nowak-Wegrzyn, MD
role: STUDY_CHAIR
References:
citation: Nowak-Wegrzyn A, Bloom KA, Sicherer SH, Shreffler WG, Noone S, Wanich N, Sampson HA. Tolerance to extensively heated milk in children with cow's milk allergy. J Allergy Clin Immunol. 2008 Aug;122(2):342-7, 347.e1-2. doi: 10.1016/j.jaci.2008.05.043. Epub 2008 Jul 11.
citation: Skripak JM, Matsui EC, Mudd K, Wood RA. The natural history of IgE-mediated cow's milk allergy. J Allergy Clin Immunol. 2007 Nov;120(5):1172-7. doi: 10.1016/j.jaci.2007.08.023. Epub 2007 Nov 1.
citation: Staden U, Rolinck-Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy. 2007 Nov;62(11):1261-9. doi: 10.1111/j.1398-9995.2007.01501.x.
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.