An Interventional Study of Milk Allergy and Tolerance in Children

• Ratio for progression in tolerance of baked milk and ultimately unheated milk in Dose escalation sub-arm compared to Maintenance sub-arm 2 [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  

• Odds ratio for progression in tolerating more allergenic forms of milk [ Time Frame: At Months 12 and 24 ] [ Designated as safety issue: No ]
  
• Percent of participants becoming tolerant to unheated cow's milk [ Time Frame: At Months 12, 24, and 36 ] [ Designated as safety issue: No ]
  
• Percent of participants who develop tolerance to unheated cow's milk [ Time Frame: Through 36 Months ] [ Designated as safety issue: No ]
  
• Correlation of baseline mechanistic studies [humoral, T cell and basophil] and stool CD23 and IgE with the outcome of the baseline OFC to identify the biomarkers of clinical reactivity and persistence of milk allergy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Relationship between initial dose of tolerated baked-milk protein and time to complete tolerance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Relationship between reactivity to casein versus whey fractions and time to complete tolerance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Relationship between dose of baked-milk protein and reactivity to casein versus whey and type of symptoms elicited during OFC [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
  
• Comparison of percent of participants tolerant to non-heated milk protein between the participants in Arms 1 and 2 [ Time Frame: At Months 12, 24, and 36 ] [ Designated as safety issue: No ]
  
• 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 [ Time Frame: Throughout the study ] [ Designated as safety issue: No ]
  

In the United States, as many as 8% of children less than three years of age are affected by food hypersensitivity. Milk is among the most common food allergens in infants and children. Although strict avoidance of milk is the current standard of care for those with milk hypersensitivity, there are data that suggest that the majority of children allergic to milk will tolerate heated milk products. Preliminary findings suggest that tolerance may be induced more quickly in those participants who ingest extensively heated, baked milk products. Therefore, a more rapid introduction of increasing doses of baked milk protein into the diet may result in accelerated development of tolerance to unheated milk. The purpose of this study is to determine whether more rapid introduction of increasingly allergenic forms of baked-milk products in baked-milk non-reactive participants shortens the time until they tolerate higher doses of less heated milk and ultimately unheated milk.

The study will last up to 46 months for each study participant. There will be two Arms: Active Treatment Arm 1 and Comparison Arm 2. At study entry, all participants in Arm 1 will undergo sequential oral food challenges (OFCs) that contain increasing amounts of baked milk protein to determine the extent to which they tolerate various baked milk proteins. The participants tolerating baked milk will then be randomly assigned to one of two sub-arms that will receive treatment with various baked milk products.

Group 1 participants who react to baked milk will continue strict milk avoidance and return for re-evaluation with baked milk challenge every 12 months until Month 36. Participants in Groups 2, 3, and 4 are tolerant to different forms of baked milk and will be randomized to return for re-evaluation every 6 or 12 months for dose escalation. In Arm 1, a review of clinical reactions, OFC, prick skin test, quality of life assessment, anthropometric measurements, mechanistic studies, and stool sample collection will occur at all study visits.

Arm 2, the comparison group, will consist of participants who fulfill inclusion criteria, but have elected not to participate in the ingestion of baked milk products. Study visits will occur at months 12, 24, and 36. A review of clinical reactions, prick skin test, quality of life assessment, mechanistic studies, and stool sample collection will occur at all study visits. OFCs are optional for participants in Arm 2.