Gut Microbial Taxonomy and Metabolism in Paediatric Crohn's Disease During Exclusive and Supplementary Enteral Nutrition Using -Omics Technologies
试验速览
- 阶段
- 不适用
- 入组人数
- 200
- 试验地点
- 5
- 主要终点
- Bacterial metabolism
研究概览
简要总结
Exclusive Enteral Nutrition (EEN) is the liquid diet given to children with active Crohn's Disease (CD). EEN has previously been shown to induce changes in major bacterial metabolites and dominant bacterial species which are more profound in children that clinically improve. This study aims to determine whether it is possible to maintain these bacterial changes with prolonged supplementary enteral nutrition (SEN) while returning to normal diet and if this can reduce risk of subsequent relapse for children with CD.
New technologies will allow measurement of a broad range of bacteria and metabolites, to test if the clinical response to EEN and changes in gut inflammation are associated with bacterial composition and chemical products; and if maintenance of changes using SEN reduces the risk of relapse over a 12 month period.
The study will aim to recruit all potential Crohn's disease children coming to a tertiary paediatric centre for colonoscopy. Once consented, an initial blood, urine and faecal sample will be requested along with 8 mucosal biopsies during the routine endoscopy session. If diagnosed with CD, and if the clinician prescribes treatment with EEN, an additional blood sample will be requested at the end of EEN, and 5 faecal and urine samples spread over 12 months; as well as some dietary information.
Samples will be collected from up to 42 children with CD and 42 age- and sex-matched healthy volunteers. Initial samples taken from children who were not diagnosed with CD will be compared with CD samples to look for potential metabolic disease markers. Characterisation of faecal bacteria and metabolites in both faeces and urine; as well as measurement of blood inflammatory biomarkers will be performed.
详细描述
The null hypothesis is that the clinical response to exclusive enteral nutrition (EEN) and reduction of colonic inflammatory markers are not associated with a characteristic bacterial taxonomy (composition) and metabolites (functionality); and that maintenance of any bacterial changes with supplementary enteral nutrition (SEN), while returning to habitual diet, does not reduce the risk of disease relapse.
The study design will build on previous work by looking at differences in both the gut bacteria (faecal and mucosal) and bacterial metabolic activity at different stages of disease activity. Changes in bacterial composition between disease groups will be examined; between Crohn's disease children on different treatments; and between different sites in the gut. Crohn's disease biomarkers in faeces and urine will also be assessed by analysing bacterial metabolites.
Up to a total of 42 children with Crohn's Disease will be recruited. 42 healthy children will also be recruited to provide a faecal and urine sample, to show the normal variety of gut bacteria and metabolites in healthy children for comparison.
Children who underwent colonoscopy but did not have Crohn's disease will be used as a comparison group to try and identify Crohn's disease bacterial signatures from faeces and urine, and as a non-Crohn's disease control group for comparison of mucosal biopsies.
Recruitment Three groups of children will participate in this study. A. Children undergoing endoscopic investigations (colonoscopy) for colonic inflammation including Crohn's disease [children who are found not to have Crohn's disease will not participate in the follow up aspect (during treatment with EEN) of this study].
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 3 Years 至 17 Years(Child)
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Group A: children with suspected Crohn's Disease with scheduled colonoscopy
- •Group B: children with existing Crohn's Disease about to undergo treatment with EEN
- •Group C: healthy volunteers up to age 17 years willing to provide one urine and stool sample
排除标准
- •children who have taken antibiotics in the previous 4 weeks
- •children found not to have Crohn's Disease after colonoscopy will not be required to take any further part in the study
结局指标
主要结局
Bacterial metabolism
时间窗: 12 months
Change in short chain fatty acid level following treatment with enteral nutrition
Gut bacterial composition
时间窗: 12 months
Change in overall gut bacteria composition following treatment with enteral nutrition
Mucosal bacterial composition
时间窗: 12 months
Change in overall bacteria composition in mucosal tissue biopsies
次要结局
- Dietary information(12 months)
- Inflammatory markers(12 months)
