Pediatric Eosinophilic Esophagitis (pedEoE): Effect of Allergen Heat Denaturation on EoE Remission: a Pilot Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 36
- 试验地点
- 2
- 主要终点
- Maintained remission of EoE
研究概览
简要总结
The objective of the study is to study whether the introduction of heated food products (more specifically heated hen's egg and/or cow's milk) in children with EoE would be possible without re-occurrence of the eosinophilic inflammation, while the intake of less heated products might cause disease recidive. Moreover, we would like to study whether the gradual re-introduction of less heated products after the most heated form is tolerated, could lead to tolerance induction in EoE.
详细描述
If inclusion criteria are met, after obtaining informed consent from the parents (and when old enough, assent from the children) children with cow's milk and/or hen's egg induced pedEoE will be included in this pilot trial. Baseline blood will be obtained before in-house OFC procedure and serum will be stored for specific IgG4 analysis. In parallel, PBMCs will be isolated and stimulated in vitro with heat denatured proteins. B cells will be stained by 4-laserflow cytometry. IgG4 production in supernatants will be studied by ELISA (specific IgG4 by Immunocap 100). This procedure will be repeated during each gastroscopy.
Children will be provoked in-house, based on the written procedure available for heated egg or cow's milk provocation. Afterwards, they will introduce heated egg by cake or 20' boiled cow's milk at least three times a week for 8 weeks and will return to the hospital for a gastroscopy with biopsies. EoE remission will be studied on biopsies of the upper and lower esophagus by eosinophil staining within the routine anatomopathological laboratory within our hospital.
If remission remains, subjects will be invited to introduce less heated hen's egg or cow's milk for 8 weeks, after which they will return to the hospital for the second gastroscopy with similar procedure. This is repeated three times until 4' soft-boiled egg or 5' boiled cow's milk is introduced for 8 weeks. When remission remains after this introduction, the children and parents are offered the possibility to terminate the study or to introduce either raw egg (tiramisu or chocolate mousse) or uncooked UHT-treated cow's milk for 8 weeks after which gastroscopy with biopsies will be performed.
If remission is lost, they will return to the strict avoidance diet for at least 10 weeks after which they will return to the hospital for their second gastroscopy. Upon remission after avoidance, the children will remain eligible for another heat denatured food challenge (when on diet for both).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 12 Months 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All children (aged 12 months and older) presenting (since 1-1-2014: moment of diagnostic guideline standardization for pedEoE) with diagnosed pedEoE at UZ Leuven eliminating either hen's egg or cow's milk or both and in complete remission after their latest biopsy (no longer than 12 months earlier, but preferentially as short as possible after their latest biopsy) are eligible for the study. If the last biopsy has been performed more than 12 months earlier, a new gastro-duodenoscopy will be performed to verify remission and rule out e.g. active gastritis. If they are on PPI and/or local budesonide treatment, this should be stable for at least 3 months and will remain untouched during the entire study. We will include 18 pedEoE subjects suffering from cow's milk induced EoE and 18 suffering from hen's egg induced EoE.
排除标准
- •Children younger than 12 months
- •Children with active pedEoE
- •Children who refuse to adhere to the protocol
- •Children with associated IgE mediated hen's egg and/or cow's milk allergy with specific IgE antibody titers that predict active (baked egg and/or baked milk) food allergy with cut-off titers as used at the consultation of allergy (KLL). Those children will become eligible however if their titers decrease while the study is still open.
结局指标
主要结局
Maintained remission of EoE
时间窗: 40 weeks
Primary end-point of the study is to study the number of pedEoE children by inclusion on hen's egg and/or cow's milk free diet with potential remaining remission (\<15 eosinophils/hpf on esophageal biopsies) after 8 weeks (re)introduction of heat-denatured hen's egg and/or cow's milk proteins (introduced sequentially as on the one hand baked egg (cake), hard-boiled egg, omelet and soft-boiled egg and on the other hand 20' cooked cow's milk, 15', 10' and 5' cooked cow's milk).
次要结局
- In vitro B cell test to mimic B cell activation after stimulation(Up to 6 months)
- Associated atopy(On inclusion with initial characteristics of the patients)
- Associated food allergies(On inclusion with initial characteristics of the patients)
- Association of remission with circulating IgG4 levels(Bloods will be taken during every gastroscopy)
- Maintained remission only in step 1 of the diet(Assessment of failed remission 8 weeks after step 2 but successful remission after step 1)
- Association of remission with IgG4 levels on biopsy(At every gastroscopy)
- Correlation between QoL and remission(Up to 45 weeks)
研究者
Dominque Bullens
Clinic Head in Pediatrics-Allergy at UZ Leuven, Head of the Allergy and Clinical Immunology Research group at KU Leuven (prof., dr.)
Universitaire Ziekenhuizen KU Leuven