Efficacy and Safety of a Four-step Goat Milk Formula-based Ladder Versus a Four-step Cow's Milk Ladder in Children With IgE-mediated Cow's Milk Allergy: Protocol for the Exploratory GOAL Randomised Controlled Trial.
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 92
- 试验地点
- 2
- 主要终点
- Between-group difference in the proportion of children who tolerate non-heated pasteurised cow's milk
研究概览
简要总结
Children with immunoglobulin E (IgE)-mediated cow's milk allergy (CMA) who react to small amounts of baked cow's milk may require prolonged elimination. Preliminary observations suggest that some may tolerate products prepared with a low-αs1-casein goat milk formula. This study will compare a four-step goat milk formula-based ladder (4-GMFL) with a four-step cow's milk ladder (4-CML).
This exploratory open-label, multicentre, randomised trial will enroll 92 children aged 1-5 years with IgE-mediated CMA, allocated 1:1 to the 4-GMFL or 4-CML group. Both ladders comprise muffin, pancake and baked hard cheese, introduced at 4-week intervals and assessed by open, physician-supervised oral food challenges (OFCs) in hospital, followed by a final OFC with 120 mL of non-heated pasteurised cow's milk at week 12.
The primary outcome will be tolerance to non-heated cow's milk protein at this final step, defined as a negative OFC with 120 mL of pasteurised cow's milk containing 3.96 g of protein. Secondary outcomes will include tolerance to individual ladder products, allergic reactions, anaphylaxis, intramuscular adrenaline use, anthropometric changes, food allergy-related quality of life, caregiver anxiety and adherence. Molecular sensitisation profiles will be explored as potential predictors of OFC outcomes.
详细描述
Goat's milk differs from cow's milk in casein composition, protein structure and digestibility. Recent data suggest that these differences may modify IgE recognition and allergenic potential. This study is based on the hypothesis that repeated exposure to goat milk formula-containing products may provide a different pattern of allergen exposure from that achieved with a conventional cow's milk ladder.
This study aims to assess the effectiveness and safety of the 4-step goat milk formula-based ladder (4-GMFL) compared to the 4-step cow's milk ladder (4-CML) in children with IgE-mediated cow's milk allergy.
An exploratory open-label randomised trial with two parallel arms in two departments: the Department of Paediatrics, Medical University of Warsaw, and the Department of Paediatrics and Allergy, Copernicus Memorial Hospital, Medical University of Lodz, will be performed. A total of 92 children with IgE-mediated cow's milk allergy will be allocated to introduce cow's milk into their diet according to either 4-GMFL or 4-CML with a 4-week break period between subsequent steps. Oral food challenge (OFCs) with tested products - muffin with goat or cow's milk formula, pancake with goat or cow's milk formula, baked goat or cow's milk hard cheese, pasteurised cow's milk - at each subsequent steps of the ladders will be conducted in hospital settings. In both groups, the final 4th ladder step is identical and will assess whether tolerance to the assigned ladder products is accompanied by tolerance to cow's milk protein.
The primary outcome will be the between-group difference in the proportion of children who acquire tolerance to non-heated pasteurised cow's milk, as determined by a negative OFC at the final step of the 4-GMFL or 4-CML. Cow's milk will be administered at the end of the observation period (12 weeks). The challenge dose will consist of 120 mL of pasteurised cow's milk, corresponding to 3.96 g of cow's milk protein.
Secondary outcomes will include between-group difference in the proportion of children with negative OFCs to each ladder steps; between-group difference in the percentage of children with anaphylaxis who required epinephrine administration; between-group difference in the percentage of children with exacerbation of atopic dermatitis; growth; compliance; Food Allergy Quality of Child's Life and the caregivers and parents' anxiety about adverse events during their child's OFC.
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
- 1 Year 至 5 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 1 and 5 years.
- •Diagnosis of IgE-mediated CMA confirmed according to ESPGHAN guidelines, by a positive OFC with CMPs. In high-risk children (i.e., with a history of anaphylaxis occurring more than 6 months before enrolment) diagnosis may be established without a new OFC, based on a positive SPT wheal at least 3 mm greater than negative saline control and elevated specific IgE to CMPs >0.35 kUa/L.
- •On a cow's milk-free, therapeutic elimination diet for at least 6 months, or since before 12 months of age.
- •Eligible regardless of the risk of systemic reaction (anaphylaxis) and asthma.
- •Overall good health status.
- •Parents/legal guardians able to understand the study procedures and communicate effectively with the study team.
- •Written informed consent provided by parents/legal guardians.
- •Expected good cooperation of the child's parents/legal guardians with the study team.
排除标准
- •Uncontrolled asthma, defined as poor control according to the current GINA criteria, recent exacerbation requiring systemic corticosteroids or the need for medium to high-dose inhaled corticosteroids to maintain control
- •Signs of acute infectious disease (i.e., acute runny nose, cough, or fever).
- •Clinically relevant, uncontrolled exacerbation of another allergic disease that, in the investigator's judgement, could compromise OFC interpretation or safety (i.e., conjunctivitis, allergic rhinitis, atopic dermatitis).
- •History of anaphylaxis due to cow's milk proteins within the last 6 months.
- •Use of antihistamines within 3-10 days before the OFC, depending on the drug's pharmacokinetics and indication (time-limited contradiction - relative exclusion criterion).
- •Documented tolerance to baked CMPs or to higher steps of the milk ladder.
- •Use of immunosuppressive drugs or ongoing allergen immunotherapy.
研究组 & 干预措施
4-step Goat Milk Formula-Based Ladder
干预措施: oral food challenge (OFC) (Other)
4-step Cow's Milk Ladder
干预措施: oral food challenge (OFC) (Other)
结局指标
主要结局
Between-group difference in the proportion of children who tolerate non-heated pasteurised cow's milk
时间窗: Non-heated pasteurised cow's milk will be administered at the end of the observation period (week 12).
The primary outcome will be the between-group difference in the proportion of children who tolerate non-heated pasteurised cow's milk. Tolerance will be defined as the absence of an allergic reaction during an OFC with 120 mL of pasteurised cow's milk, corresponding to 3.96 g of cow's milk protein. In both the 4-CML and 4-GMFL groups, this OFC constitutes Step 4 and the final step of the ladder.
次要结局
- Between-group difference in the proportion of children tolerating the full predefined dose at Steps 1-3(Baseline (Step 1), week 4 (Step 2) and week 8 (Step 3))
- Between-group difference in maximum tolerated dose at each ladder step(Baseline (Step 1), week 4 (Step 2) and week 8 (Step 3))
- Between-group difference in the percentage of children who experienced anaphylaxis(Measured during the observation period (12 weeks).)
- Between-group difference in the proportion of children with anaphylaxis (grades 3-5, per 2023 WAO criteria) who required epinephrine administration(Measured during the observation period (12 weeks).)
- Between-group differences in anthropometric changes(Measured during the observation period (12 weeks).)
- Between-group difference in the change in the total score of the FAQLQ-PF(At the end of the observation period (12 weeks) from baseline.)
- Between-group differences in caregiver anxiety levels, measured by the Subjective Units of Distress Scale (SUDS)(Before each OFC at baseline, week 4, week 8 and week 12)
- Between-group difference in full adherence to the intervention protocol(At the end of the observation period (12 weeks).)
- In the subgroup of children with atopic dermatitis, changes in the total score of the oSCORAD index will be assessed before and after each OFC.(Upon completion of the observation period (12 weeks))
研究者
Andrea Horvath-Stolarczyk
Professor
Medical University of Warsaw