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一项评估粪菌移植在儿童克罗恩病人群中可行性和疗效的双盲、随机、安慰剂对照的初步研究方案:PediCRaFT 试验。

Protocol for a double-blind, randomised, placebo-controlled pilot study for assessing the feasibility and efficacy of faecal microbiota transplant in a paediatric Crohn's disease population: PediCRaFT Trial.

机构信息

Pediatrics, Division of Pediatric Gastroenterology and Nutrition, McMaster University, Hamilton, Ontario, Canada

Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Ontario, Canada.

出版信息

BMJ Open. 2019 Nov 28;9(11):e030120. doi: 10.1136/bmjopen-2019-030120.


DOI:10.1136/bmjopen-2019-030120
PMID:31784432
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6924772/
Abstract

INTRODUCTION: Crohn's disease (CD) is a chronic inflammatory condition with transmural involvement of the gastrointestinal tract. Extraintestinal manifestations are common, and the disease burden on patients and the healthcare system is significant. While treatment options have expanded in recent years, they have mainly focused on dampening the immune response, thus carrying notable risks associated with long-term immunosuppression. Faecal microbiota transplant (FMT) targets inflammatory bowel disease (IBD) by modifying intestinal dysbiosis. Limited adult and paediatric data have demonstrated a favourable response to FMT in IBD; however, no randomised controlled trial has yet been published in paediatrics. This double-blind, randomised, placebo-controlled pilot study will assess feasibility and efficacy outcomes of FMT in a paediatric CD population. METHODS AND ANALYSIS: Forty-five patients between the ages of 3 and 17 years, with established CD or IBD unclassified, will be enrolled 2:1 to undergo FMT intervention or placebo control. Participants will undergo a colonoscopic infusion to the terminal ileum at baseline, followed by oral capsules two times per week for 6 weeks. Outcomes will be measured throughout the intervention period and 18 weeks of subsequent follow-up. Primary outcomes will assess feasibility, including patient recruitment, sample collection and rates of adverse events. Secondary outcomes will address clinical efficacy, including change in clinical response, change in urine metabolome and change in microbiome. ETHICS AND DISSEMINATION: Ethics approval from the local hospital research ethics board was obtained at the primary site (McMaster Children's Hospital, Hamilton), with ethics pending at the secondary site (Centre Hospitalier Universitaire-Sainte-Justine, Montréal). RBX7455 and RBX2660 are human donor-sourced, microbiota-based therapeutic formulations. Both RBX7455 and RBX2660 are currently undergoing clinical trials to support potential US Food and Drug Administration approval. Approval to conduct this paediatric clinical trial was obtained from Health Canada's Biologics and Genetic Therapies Directorate. The results of this trial will be published in peer-reviewed journals and will help inform a large, multicentre trial in the future. TRIAL REGISTRATION NUMBER: NCT03378167; pre-results.

摘要

介绍:克罗恩病(CD)是一种胃肠道黏膜全层受累的慢性炎症性疾病。肠道外表现很常见,疾病给患者和医疗系统带来的负担都很沉重。近年来,治疗方案虽有所扩展,但主要集中在抑制免疫反应上,因此长期免疫抑制相关的风险显著。粪便微生物群移植(FMT)通过改变肠道菌群失调来靶向治疗炎症性肠病(IBD)。虽然有限的成人和儿科数据表明 FMT 对 IBD 有良好的反应,但在儿科领域尚未发表随机对照试验。这项双盲、随机、安慰剂对照的初步研究将评估 FMT 在儿科 CD 人群中的可行性和疗效。 方法和分析:将招募 45 名 3 至 17 岁的已确诊 CD 或未分类 IBD 的患者,按照 2:1 的比例进行 FMT 干预或安慰剂对照。参与者将在基线时进行末端回肠的结肠镜下输注,然后每周口服两次胶囊,持续 6 周。结果将在整个干预期间和随后的 18 周随访中进行测量。主要结果将评估可行性,包括患者招募、样本采集和不良事件发生率。次要结果将评估临床疗效,包括临床反应的变化、尿液代谢组的变化和微生物组的变化。 伦理和传播:主要地点(汉密尔顿麦克马斯特儿童医院)已获得当地医院研究伦理委员会的伦理批准,次要地点(蒙特利尔圣贾斯汀中心医院)的伦理正在等待中。RBX7455 和 RBX2660 是源自人类供体的微生物群治疗制剂。RBX7455 和 RBX2660 目前都在进行临床试验,以支持潜在的美国食品和药物管理局批准。加拿大卫生部生物制品和基因治疗局批准了进行这项儿科临床试验。这项试验的结果将在同行评议的期刊上发表,并将有助于为未来的大型多中心试验提供信息。 试验注册号:NCT03378167;预结果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eda/6924772/bda70e3b71d2/bmjopen-2019-030120f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eda/6924772/8b8cde9357ab/bmjopen-2019-030120f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eda/6924772/bda70e3b71d2/bmjopen-2019-030120f02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eda/6924772/8b8cde9357ab/bmjopen-2019-030120f01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2eda/6924772/bda70e3b71d2/bmjopen-2019-030120f02.jpg

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本文引用的文献

[1]
Safety and preliminary efficacy of orally administered lyophilized fecal microbiota product compared with frozen product given by enema for recurrent Clostridium difficile infection: A randomized clinical trial.

PLoS One. 2018-11-2

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JAMA. 2017-11-28

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Inflamm Bowel Dis. 2017-10

[7]
Protocol for a randomised, placebo-controlled pilot study for assessing feasibility and efficacy of faecal microbiota transplantation in a paediatric ulcerative colitis population: PediFETCh trial.

BMJ Open. 2017-8-21

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Systematic review with meta-analysis: faecal microbiota transplantation for the induction of remission for active ulcerative colitis.

Aliment Pharmacol Ther. 2017-8

[9]
Editorial: Making Fecal Microbiota Transplantation Easier to Swallow: Freeze-Dried Preparation for Recurrent Clostridium difficile Infections.

Am J Gastroenterol. 2017-6

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Immunity. 2017-4-18

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