PROBIOTICS IN PEDIATRIC DIARRHEA IN PERU: PLANNING GRANT

秘鲁益生菌治疗小儿腹泻：规划拨款

• 批准号: 6849167
• 负责人: RICHARD A OBERHELMAN
• 金额: $ 13.07万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-02-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6849167
• 关键词: Campylobacter; Escherichia coli; Giardia; Lactobacillus; Peru; Rotavirus; Shigella; biotherapeutic agent; breast feeding; children; clinical trial phase III; data collection methodology /evaluation; diarrhea; drug adverse effect; drug screening /evaluation; gram positive bacteria; health care cost /financing; human therapy evaluation; low socioeconomic status; malnutrition; medically underserved population; method development; pediatrics; rural area

DESCRIPTION (provided by applicant): Diarrhea causes a billion illness episodes and 2.5 million deaths/year in children under the age of 5 years in the developing world and China. Oral rehydration therapy has reduced mortality from this disease, but repeated episodes of diarrhea still affect many children in the developing world, contributing to the problem of malnutrition. Probiotic bacteria have been shown to be effective for treatment of pediatric diarrhea in many studies, but variations in study design, probiotic agents used, and causes of diarrhea make it difficult to determine the most appropriate role for probiotics in childhood diarrhea in malnourished populations from developing countries. This proposal is submitted to the R34 NIH Clinical Trial Planning Grant Program to support development of a Phase III clinical trial evaluating the relative efficacy of the most promising probiotic agents for treatment of diarrhea in a population representative of high-risk undernourished children around the world, examining practical issues of cost and distribution, adverse effects, the impact of breast feeding, and pathogen-specific responses. The investigators will build on their extensive experience in community based clinical trials in Peru by supporting the necessary but time consuming work needed to prepare for a successful clinical trial with the current grant. The principal investigator will work with Peru-based consultants to build laboratory and field site capabilities in the community of Santa Clara, Peru, a rural community in the Amazon Basin located 10 km. from the urban center of Iquitos. This community has been the site of an ongoing successful longitudinal surveillance study of Shigella transmission, and it was chosen as a site for the probiotics clinical trial due to high rates of diarrhea and childhood malnutrition. The planning grant will be used to support investigator time, travel expenses, and equipment needed for 1) developing an ongoing mechanism for census data collection to identify potential subjects for the clinical trial, 2) training and infrastructure improvements in the clinical laboratory to optimize capability for diagnostic testing of diarrhea cases, microbiologic methods for quality control, and evaluation of adverse events, 3) discussions with manufacturers of probiotic products to be included in the clinical trial, 4) obtaining agreements for administration and human subjects monitoring from involved institutions, including the establishment of a Data Safety Monitoring Board and Certification Training, 5) establishing Standard Operating Procedures (SOP) and documentation Procedures for the clinical trial phase, along with tools for data collection and procedures for periodic analyses, and 6) development of dialog with the community to build support for the trial and address concerns. Support for these activities during a planning period before the clinical trial will greatly facilitate the implementation of the trial.

描述（由申请人提供）：在发展中国家和中国，腹泻每年导致 5 岁以下儿童发生 10 亿次疾病和 250 万人死亡。口服补液疗法降低了这种疾病的死亡率，但腹泻的反复发作仍然影响着发展中国家的许多儿童，导致营养不良问题。许多研究已证明益生菌可有效治疗儿童腹泻，但研究设计、使用的益生菌制剂以及腹泻原因的差异使得很难确定益生菌在发展中国家营养不良人群儿童腹泻中的最合适作用。该提案已提交给 R34 NIH 临床试验规划拨款计划，以支持开展 III 期临床试验，评估最有前途的益生菌制剂治疗全球高危营养不良儿童代表人群腹泻的相对功效，并研究成本和分配、不良反应、母乳喂养的影响和病原体特异性反应等实际问题。研究人员将利用他们在秘鲁社区临床试验的丰富经验，支持利用当前拨款为成功的临床试验做准备所需的必要但耗时的工作。首席研究员将与秘鲁的顾问合作，在秘鲁圣克拉拉社区建立实验室和现场能力，圣克拉拉是距离亚马逊盆地 10 公里的一个农村社区。从伊基托斯市中心出发。该社区一直是一项持续成功的志贺氏菌传播纵向监测研究的地点，并且由于腹泻和儿童营养不良的高发生率而被选为益生菌临床试验的地点。规划拨款将用于支持研究人员的时间、差旅费和所需设备：1）开发持续的普查数据收集机制，以确定临床试验的潜在受试者，2）临床实验室的培训和基础设施改进，以优化腹泻病例的诊断测试、质量控制的微生物学方法和不良事件评估的能力，3）与益生菌产品制造商进行讨论，以纳入研究 临床试验，4) 从相关机构获得管理和人体受试者监测协议，包括建立数据安全监测委员会和认证培训，5) 建立临床试验阶段的标准操作程序 (SOP) 和记录程序，以及数据收集工具和定期分析程序，以及 6) 与社区开展对话，为试验提供支持并解决问题。在临床试验前的规划期间对这些活动的支持将极大地促进试验的实施。