Study of Milk Allergy and Tolerance in Children

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase: Completed; Phase 2

Conditions: Milk Hypersensitivity; Food Hypersensitivity

Treatments: Biological: Non-baked Milk; Biological: Baked Milk

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00778258

DAIT AADCRC-MSSM-02

Details and patient eligibility

About

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.

Full 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.

Enrollment: 170 patients

Sex: All

Ages: 4 to 10 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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170 participants in 6 patient groups

Milk-allergic; Non-consumption

Experimental group

Description:

Subjects in this arm reacted to the lowest baseline dose of baked milk (muffin) and will continue strict milk avoidance, returning for re-evaluation with laboratory tests at 12 and 24 months and baked milk challenge at 36 months. Individual participants may be challenged at 12 and or 24 months.

Treatment:

Biological: Baked Milk

Tolerated Muffin, Reacted to Pizza

Experimental group

Description:

Subjects will be assigned to this arm, if they can tolerate ingesting a muffin but react to ingesting the amount of baked milk in a standardized portion of pizza. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein.

Treatment:

Biological: Baked Milk

Reacted to Rice Pudding

Experimental group

Description:

Subjects will be assigned to this arm, if they can tolerate ingesting a muffin and a standardized portion of pizza but react to a standardized dose of baked milk in rice pudding. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein.

Treatment:

Biological: Baked Milk

Reacted to Non-baked Milk

Experimental group

Description:

Subjects will be assigned to this arm, if they can tolerate ingesting a muffin, pizza and rice pudding but react to a standardized dose of non-baked milk. Within the arm, subjects will be randomized in 1:1 ratio to either return for re-evaluation at 6 months (Dose Escalation sub-arm) or 12 months (Maintenance sub-arm) to determine whether they might progress to ingesting higher amounts of baked milk protein.

Treatment:

Biological: Baked Milk

Biological: Non-baked Milk

Tolerant to Baked and Non-baked Milk

Experimental group

Description:

Biological/Vaccine: Baked Milk At baseline, each subject will undergo sequential oral food challenges with the products that contain increasing amounts of milk protein that are baked: Stage 1 (muffin), Stage 2 (pizza), and Stage 3 (rice pudding) doses of baked milk to determine the extent to which they tolerate various baked milk proteins. Based on the outcomes of the baseline oral food challenges, subjects will be assigned to one of the 5 study arms. Biological/Vaccine: Non-baked Milk Those subjects tolerant to rice pudding will undergo oral food challenge with non-baked milk.

Treatment:

Biological: Baked Milk

Biological: Non-baked Milk

Non-Interventional Comparison

No Intervention group

Description:

Thirty subjects who fulfill inclusion criteria but are unwilling to participate in the full protocol will be enrolled as a comparison group to the active arms.