Effects of alanyl-glutamine supplementation on C. difficile associated diarrhea

补充丙氨酰谷氨酰胺对艰难梭菌相关性腹泻的影响

• 批准号: 8669628
• 负责人: Cirle Alcantara Warren
• 金额: $ 23.7万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-03 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8669628
• 关键词: Acute; Animal Model; Animals; Antibiotic Therapy; Antibiotics; Apoptosis; Body Weight decreased; Caring; Cell Line; Cell Proliferation; Cells; Cessation of life; Clinical Protocols; Clinical Trials; Clostridium difficile; Conduct Clinical Trials; Consent Forms; Data; Development; Diarrhea; Dipeptides; Disease; Epithelial; Evaluation; Glutamine; Grant; Healthcare; Histopathology; Human; Human Resources; Impairment; In Vitro; Infection; Inflammatory disease of the intestine; Institutional Review Boards; Intestinal Secretions; Intestines; Manuals; Mediating; Monitor; Mus; Nosocomial Infections; Nutritional; Oral; Outcome; Patients; Performance; Pharmaceutical Preparations; Physiologic pulse; Prevention; Recurrence; Recurrent disease; Relapse; Reporting; Research; Running; Safety; Supplementation; Testing; Tissues; Toxin; Training; Treatment outcome; Vancomycin; alanylglutamine; caspase-8; cell motility; cost; data management; efficacy testing; human disease; improved; in vivo; microbial; mortality; mouse model; novel strategies; operation; prevent; public health relevance; repaired; restoration; standard care; tool

DESCRIPTION (provided by applicant): C. difficile is a leading cause of antibiotic-associated diarrhea and nosocomial infection. Antibiotic treatment is the standard approach in managing C. difficile infection (CDI) and is associated with recurrence rates of up to 65% depending on the number of previous disease. Alanyl-glutamine prevents C. difficile toxin-induced impairment of cell migration and proliferation in intestinal cell lines, secretion and histopathology in animal ieal tissues, and increased apoptosis in vitro and in vivo. Recently, we have shown that in the mouse model of CDI, alanyl-glutamine supplementation significantly reduced diarrhea, weight loss, histopathology, relapse and deaths in vancomycin-treated mice. We hypothesize that supplementation with alanyl-glutamine will improve outcomes of treatment of CDI in humans. To prove this hypothesis, the planned clinical trial will have 2 specific aims. First, we shall test te effect of oral supplementation with alanyl-glutamine on duration of diarrhea, recurrence and deaths in patients treated with standard anti-C.difficile agents. Secondly, we shall test the effec of alanyl-glutamine on intestinal inflammation, barrier function and gut flora in patients undergoing standard treatment for CDI. To adequately prepare for the clinical trial, this proposal will have the following specific aims: (1) Establish and prepare the research team to run the clinical trial; (2) Develop documents needed for the clinical trial; and (3) Develop tools that are required for the evaluation of the clinical trial. The planning grant will allow for a rigorous, sae, effective and productive performance of the clinical trial to prove the benefit of alanyl-glutamine in human disease, potentially introducing a novel approach to treatment of CDI.

描述（由申请人提供）：艰难梭菌是抗生素相关腹泻和医院感染的主要原因。抗生素治疗是管理艰难梭菌感染（CDI）的标准方法，并且根据先前疾病的数量，复发率高达65％。丙酰谷氨酰胺可防止艰难梭菌毒素诱导的细胞迁移损伤和肠细胞系中的增殖，动物IEAL组织中的分泌和组织病理学的增殖，并在体外和体内增加凋亡。最近，我们表明，在CDI的小鼠模型中，补充丙氨酸谷氨酰胺可显着降低腹泻，体重减轻，组织病理学，复发和死亡的小鼠死亡。我们假设补充丙酰基谷氨酰胺将改善人类CDI治疗的结果。为了证明这一假设，计划的临床试验将具有2个具体目标。首先，我们应测试用标准抗C.缺陷剂治疗的患者，用丙酰 - 谷氨酰胺补充口服对腹泻，复发和死亡的影响。其次，我们应测试接受CDI标准治疗的患者的肠道炎症，屏障功能和肠道菌群的EFEC。为了充分准备临床试验，该提案将具有以下具体目标：（1）建立并准备研究小组进行临床试验； （2）开发临床试验所需的文件； （3）开发工具 评估临床试验所必需的。规划赠款将允许临床试验的严格，SAE，有效和富有成效的表现，以证明丙氨酸的好处 在人类疾病中，有可能引入一种新型的CDI治疗方法。