Clinical trial exploring the diet-microbiome axis in allo-HCT patients

探索异基因 HCT 患者饮食-微生物组轴的临床试验

• 批准号: 10441583
• 负责人: MUNEESH TEWARI
• 金额: $ 43.96万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10441583
• 关键词: Acute; Acute Graft Versus Host Disease; Allogenic; Bacteria; Benign; Bile Acids; Bioinformatics; Biological; Biometry; Butyrates; Cell Therapy; Clinic; Clinical; Clinical Data; Clinical Trials; Collection; DNA; Data; Death Rate; Development; Diet; Dietary Intervention; Dietary Supplementation; Digestive System Disorders; Disease; Enzymes; Epithelial Cells; Face; Feces; Gastrointestinal tract structure; Hematological Disease; Hematology; Hematopoietic Stem Cell Transplantation; Human; Immunocompromised Host; Immunosuppression; Incidence; Institution; Intervention; Intestines; Joints; Laboratories; Life; Malignant - descriptor; Measurement; Mediating; Metabolism; Metagenomics; Microbe; Mus; Pathogenesis; Patient-Focused Outcomes; Patients; Phase II Clinical Trials; Pilot Projects; Plasma; Plasma Cells; Play; Potato; Probiotics; RNA; Reporting; Research; Research Personnel; Resistance; Role; Safety; Savings; Severities; Severity of illness; Specimen; Starch; T-Lymphocyte; Technology; Testing; Tissues; Translating; Volatile Fatty Acids; Work; base; bench to bedside; cost; dietary; dietary manipulation; epithelial injury; fecal transplantation; gastrointestinal; gastrointestinal epithelium; graft vs host disease; gut bacteria; gut microbiome; gut microbiota; host microbiota; improved; improved outcome; intestinal epithelium; member; metabolome; metabolomics; microbial; microbiome; microbiome alteration; microbiome composition; microbiome therapeutics; microbiota metabolites; mortality; mouse model; new technology; novel; phase II trial; pre-clinical; prebiotics; prophylactic; safety and feasibility; standard of care; stool sample

PROJECT SUMMARY/ABSTRACT – PROJECT 4 Allogeneic hematopoietic stem cell transplantation (allo-HCT) is a potent form of cellular therapy that has the potential to cure malignant and benign hematological conditions. However, its utility is limited by the development of graft-versus-host disease (GVHD). GI GVHD is the principal cause of non- relapse mortality (NRM) after allo-HCT. Recent evidence has brought into focus the role played by the metabolites derived from host-microbiota interactions in the severity of GI GVHD. However, the biological mechanisms, clinical feasibility, and the impact of altering the GI microbial metabolites on GI GVHD remain unknown. Project 4 will focus on dietary manipulation of the microbiome-metabolomic axis via dietary supplementation with resistant potato starch (RPS) for mitigating GVHD in allo-HCT patients. This project encompasses an investigator initiated proof-of-concept clinical trial that has been developed to translate the preliminary data generated from Projects 1 and 3. This trial is being performed under an IND from the FDA. It includes serial biosample (stool and plasma) collection and analyses for the microbiota and metabolite alterations, informed by mechanistic studies from projects 1, 2, and 3. We will also combine these data with longitudinal measurement of molecules reflecting intestinal epithelial injury, collectively comprising discovery approaches to more comprehensively study the effects of RPS on the microbiome, its dependent metabolites and host in allo-HCT patients.

项目摘要/摘要 - 项目4 同种异体造血干细胞移植（Allo-HCT）是细胞疗法的潜在形式 有可能治愈恶性和良性血液学状况。但是，它的效用是有限的 通过移植抗宿主病（GVHD）的发展。 GI GVHD是非 - Allo-HCT后复发死亡率（NRM）。最近的证据使重点是 源自GI GVHD严重程度的宿主 - 微生物群相互作用的代谢产物。但是， 生物学机制，临床可行性以及改变GI微生物代谢物对GI的影响 GVHD仍然未知。项目4将集中于微生物组 - 代谢组的饮食操纵 通过饮食补充轴抗耐药的马铃薯淀粉（RPS），用于缓解Allo-HCT中的GVHD 患者。该项目涵盖了一个调查员发起的概念证明临床试验 开发以翻译项目1和3产生的初步数据。该试验正在 在FDA的IND下进行。它包括串行生物样品（粪便和等离子体）集合和 对菌群和代谢物改变的分析，通过项目1的机械研究告知 2和3。我们还将将这些数据与反映分子的纵向测量结合在一起 肠上皮损伤，共同完成发现方法以进行更全面的研究 RPS对微生物组，其依赖的代谢产物和宿主的影响。