Dietary Intervention in Milk Allergy and Tolerance Development
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 170
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Years 至 10 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •Inability or unwillingness of a participant to give written informed consent or to comply with study protocol
研究组 & 干预措施
Milk-allergic; Non-consumption
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.
干预措施: Baked Milk (Biological)
Tolerated Muffin, Reacted to Pizza
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.
干预措施: Baked Milk (Biological)
Reacted to Rice Pudding
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.
干预措施: Baked Milk (Biological)
Reacted to Non-baked Milk
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.
干预措施: Baked Milk (Biological)
Reacted to Non-baked Milk
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.
干预措施: Non-baked Milk (Biological)
Tolerant to Baked and Non-baked Milk
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.
干预措施: Baked Milk (Biological)
Tolerant to Baked and Non-baked Milk
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.
干预措施: Non-baked Milk (Biological)
Non-Interventional Comparison
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.
结局指标
主要结局
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
时间窗: Randomization through end of study (up to 36 months)
Participants were grouped based on the food to which they experienced a reaction at the baseline Oral Food Challenge (OFC). Group 1=reacted to muffin; Group 2=reacted to pizza; Group 3=reacted to rice pudding; Group 4=reacted to non-baked milk; Group 5=did not react. Groups 2, 3, and 4 were randomized to dose escalation or maintenance, and at each visit following randomization, participants performed an OFC where they were given food products containing milk protein denatured through baking. Participants were given progressively less denatured milk protein food items until they had an allergic reaction. Participants were considered to have a positive progression in tolerance of baked milk if they experienced a reaction to a less denatured milk protein food item at any post randomization visits than the one to which they reacted at their baseline visit.
次要结局
- Percent of Participants Becoming Tolerant to Unheated Cow's Milk at 12, 24, and 36 Months(12 months, 24 months, and 36 months)
- Percent of Participants Becoming Tolerant to Unheated Cow's Milk(Randomization through end of study (up to 36 months))
- Comparison of Baseline IgE With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity(Baseline)
- Comparison of Baseline Mechanistic Studies [Treg and Basophil] With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity(Baseline)
- Relationship Between Initial Dose of Tolerated Baked-milk Protein and Time to Complete Tolerance(Randomization through end of study (up to 36 months))
- 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(Month 36)
- Changes in Mechanistic Values [Humoral, T Cell and Basophil](Baseline to the time complete milk tolerance was established)
- Number of Participants With a Positive Progression in Tolerating More Allergenic Forms of Milk at 12 and 24 Months(12 months, 24 months)
- Comparison of Baseline Basophil Percent Maximal Degranulation With the Outcome of the Baseline OFC to Identify the Biomarkers of Clinical Reactivity(Baseline)
- Relationship Between Dose of Baked-milk Protein and Reactivity to Casein Versus Whey(Baseline, Month 12, Month 24, Month 36)
- Changes in Mechanistic Values [Humoral, T Cell and Basophil](Baseline, Month 12, Month 24, and Month 36)