A randomized, placebo-controlled clinical trial examining the efficacy of Fecal Microbiota Transplantation (FMT) and subsequent dietary fiber in patients with moderate ulcerative colitis (MINDFUL)

一项随机、安慰剂对照临床试验，检验粪便微生物群移植 (FMT) 和随后的膳食纤维对中度溃疡性结肠炎 (MINDFUL) 患者的疗效

• 批准号: 10631895
• 负责人: randy s longman
• 金额: $ 33.9万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10631895
• 关键词: Affect; American; Animal Model; Bacteria; Biological; Cell physiology; Cells; Clinical; Clinical Research; Colitis; Complex; Computer software; Data; Diet; Dietary Fiber; Dietary Intervention; Dietary Supplementation; Engraftment; Enzymes; Fiber; Immune; Immunity; Immunologics; Inflammatory Bowel Diseases; Intervention; Intestines; Medical; Metagenomics; Microbe; Mucositis; Nutrient; Outcome; Participant; Patients; Pharmaceutical Preparations; Placebos; Polysaccharides; Psyllium; Randomized; Randomized, Controlled Trials; Refractory Disease; Research; Research Infrastructure; Resources; Role; Shapes; Source; Supplementation; Testing; Ulcerative Colitis; Volatile Fatty Acids; Work; bioinformatics pipeline; chronic inflammatory disease; clinical efficacy; clinical infrastructure; clinical remission; design; double-blind placebo controlled trial; effective therapy; efficacy evaluation; fecal transplantation; follow-up; gut inflammation; gut microbiome; healing; improved; inclusion criteria; meetings; metabolomics; microbial; microbiome; microbiome analysis; microbiota; novel; novel strategies; novel therapeutic intervention; open label; pre-clinical research; prebiotics; primary endpoint; randomized placebo-controlled clinical trial; response; secondary endpoint

Ulcerative colitis (UC) is a chronic inflammatory disease of the intestine affecting over 1 million Americans. Despite advances in medical therapies, nearly half of the patients requiring biologic medications will develop medically refractory disease. As such, there is an urgent need for new treatment approaches for UC. Emerging data from several randomized controlled trials (RCTs) suggest that fecal microbiota transplantation (FMT) is safe and effective for the treatment of UC. Although extensive pre-clinical research showing a central role for the gut microbiome in regulating animal models of colitis support these encouraging clinical findings, variability in the efficacy of FMT for UC has limited the clinical impact. Research from our own group and others has shown that the composition of the donor microbiome is associated with clinical response. Our preliminary data extend these findings with strain level characterization showing that a core transferable microbiota correlates with clinical response to FMT in UC. A detailed understanding of the mechanisms that promote the transfer and engraftment of these beneficial bacteria is needed to enhance the clinical efficacy of FMT for UC. Diet is a critical regulator of the intestinal microbiome and its subsequent impact on intestinal inflammation, but the effect of diet and/or prebiotic supplementation on microbial engraftment and clinical outcome following FMT has never been tested. It is, therefore, a critical need to assess the role for dietary interventions in shaping the microbiome and clinical outcomes of FMT for UC. This proposal will evaluate the fundamental hypothesis that dietary fiber supplementation can improve the clinical efficacy of FMT by shaping microbial engraftment and function of specific transferable microbes. We propose the following aims to evaluate this hypothesis: (i) to test the potential impact of fiber to improve clinical outcomes of FMT for UC with a randomized, double-blind, placebo-controlled trial of FMT with or without open-label dietary fiber supplementation for the treatment of mild to moderate UC; (ii) to define the impact of fiber supplementation on microbial engraftment and immune cell function after FMT in patients with UC. If successful, our study will offer critical support for the role of dietary fiber in shaping the outcome of FMT. Furthermore, our microbiome, metabolomic, and immunologic characterization will provide key mechanistic analysis to support the design of larger follow-up clinical studies. Given the feasibility and practicality of this intervention, results from this work have the potential to transform FMT for UC as well as other indications.

溃疡性结肠炎（UC）是肠道的一种慢性炎症性疾病，影响了100万美国人。 尽管医疗疗法进展，需要生物药物的患者中有将近一半 医学上难治性疾病。因此，迫切需要为UC采用新的治疗方法。 来自几个随机对照试验（RCT）的新兴数据表明，粪便菌群移植 （FMT）对于UC的治疗是安全且有效的。尽管广泛的临床前研究表明了中心 肠道微生物组在调节结肠炎动物模型中的作用支持这些令人鼓舞的临床发现， FMT对UC的疗效的可变性限制了临床影响。我们自己的小组的研究 其他人则表明，供体微生物组的组成与临床反应有关。我们的 初步数据以应变水平表征扩展了这些发现，表明核心可转移 微生物群与UC中对FMT的临床反应相关。对机制的详细理解 需要促进这些有益细菌的转移和植入，以增强 FMT用于UC。饮食是肠道微生物组的关键调节剂，其随后对肠道的影响 炎症，但饮食和/或益生元补充对微生物植入和临床的影响 FMT之后的结果从未进行过测试。因此，这是评估饮食作用的迫切需要 塑造UC的FMT的微生物组和临床结果的干预措施。该建议将评估 基本假设，即补充饮食纤维可以通过成型来提高FMT的临床功效 特定可转移微生物的微生物植入和功能。我们建议以下目标 评估这一假设：（i）测试纤维对改善UC的FMT临床结果的潜在影响 FMT的随机，双盲，安慰剂对照试验，带有或不带有标签的饮食纤维 补充治疗轻度至中度UC的治疗； （ii）定义纤维补充对 FMT后的微生物植入和免疫细胞功能在UC患者中。如果成功，我们的研究将提供 饮食纤维在塑造FMT结果中的作用的重要支持。此外，我们的微生物组， 代谢组和免疫学表征将提供关键的机械分析，以支持设计 更大的随访临床研究。鉴于这种干预的可行性和实用性，这项工作是由此造成的 有可能转换UC以及其他指示的FMT。