Efficacy of the "Milk Ladder" Intervention in the Development of Tolerance and the Recognition of B Cell Epitopes in Babies Who Are Allergic to Cow's Milk Proteins
试验速览
- 阶段
- 不适用
- 入组人数
- 114
- 试验地点
- 2
- 主要终点
- Number of participants that develop tolerance to milk after the 'Milk Ladder' intervention
研究概览
简要总结
Food allergies have become a relevant health problem in westernized societies, particularly, with children. Cow's milk (CM), along with hen's eggs, are the most common foods eliciting allergic reactions in children under 4 years of age. The main objective of this intervention study is to evaluate the safety and efficacy of the intervention known as "The Milk Ladder" in the development of tolerance by children with CM allergies. This will be compared to an historical cohort (CoALE), which investigated the natural history of this allergy. Additionally, the ability of informative epitopes will be evaluated for their potential to predict tolerance and their correlation against clinical variables.
The "Milk Ladder" will be evaluated within a prospective cohort of CM allergic children. This intervention is enacted through the introduction of meals cooked with progressively increasing amounts of cow's milk into the participant's diet. The primary outcome will be the development of tolerance which will be evaluated through a double-blind placebo-controlled food challenge. IgE and IgG4 epitopes will be described using a peptide microarray immunoassay. Quality of life will be determined by administering the FAQLQ-PF disease-specific questionnaire. Finally, within a subgroup of study participants, the ability of different peptides to activate basophils will be analyzed, and CM T cell epitopes will be studied by means of T-cell proliferation and cytokine production assays.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Month 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Babies of both sexes.
- •Age < 12 months.
- •Clinical history of immediate reaction (<2 hours) after the intake of baby's formula and/or foods containing cow's milk.
- •Sensitization to cow's milk proteins demonstrated by:
- •sIgE to cow's milk, alpha-Lactoabumin, beta-Lactoglobulin and/or Casein >0.1KU/l (ImmunoCAP®, ThemoFisher) and/or
- •Skin prick test to cow's milk, alpha-Lactoabumin, beta-Lactoglobulin and/or Casein ≥3mm
- •If the reaction to milk occurred over 3 months before the recruitment, it will be mandatory to confirm reactivity to milk with an oral food test.
- •Parents / legal representatives of the participant voluntary accept to participate.
排除标准
- •Delayed reactions (> 2 h) after milk intake.
- •Contact urticaria to milk if ingestion is well tolerated.
- •Previous participation in oral tolerance induction/desensitization protocols.
- •Treatment with any medication that might interfere the evaluation of the primary outcome or any study procedure.
- •Any disease or condition which presents a contraindication to perform an oral challenge, either open or double-blind or any other study procedure.
- •Social circumstances that might interfere with protocol adherence.
- •Egg and/or wheat allergy (this exclusion criterion shall be verified before the beginning of the intervention).
结局指标
主要结局
Number of participants that develop tolerance to milk after the 'Milk Ladder' intervention
时间窗: 12 months
Tolerance assessment: participants who successfully pass a double-blind placebo-controlled oral food challenge without experiencing any limiting symptom
Number of participants experiencing any adverse reaction
时间窗: 12 months
Number of participants experiencing any adverse reaction to milk-containing foods along the intervention assessed by Medical Dictionary for Regulatory Activities (MedDRA), version in place at the end of the study.
Change in antigen-specific IgE and IgG4 epitopes repertoire
时间窗: 6 and 18 months
Serum specific inmunnoglobulin levels using a milk peptide microarray immunoassay
次要结局
- Quality of life(6 and 18 months)
- Potential T-cell epitopes(12 months)
- Ability of the milk allergenic peptides to activate basophils(12 months)
研究者
Inmaculada Cerecedo
Principal Investigator
Hospital San Carlos, Madrid