PROBIOTICS IN PEDIATRIC DIARRHEA IN PERU: PLANNING GRANT

描述(申请人提供)：在发展中国家和中国，腹泻每年导致10亿例5岁以下儿童发病和250万人死亡。口服补液疗法降低了这种疾病的死亡率，但反复发作的腹泻仍然影响着发展中国家的许多儿童，加剧了营养不良的问题。在许多研究中，益生菌已被证明是治疗儿童腹泻的有效方法，但由于研究设计、益生菌制剂的使用和腹泻原因的不同，很难确定益生菌在发展中国家营养不良人群的儿童腹泻中最合适的作用。这项建议被提交给R34 NIH临床试验计划资助计划，以支持第三阶段临床试验的开发，评估最有希望的益生菌制剂在世界各地具有高危营养不良儿童代表的人群中治疗腹泻的相对有效性，检查成本和分配、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。研究人员将以他们在秘鲁社区临床试验方面的丰富经验为基础，支持必要但耗时的工作，以利用当前的赠款为成功的临床试验做准备。首席调查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，圣克拉拉是亚马逊盆地10公里处的一个农村社区。从伊基托斯市中心出发。这个社区一直是志贺氏菌传播的持续成功的纵向监测研究的地点，由于腹泻和儿童营养不良的高比率，这里被选为益生菌临床试验的地点。计划拨款将用于支持研究人员的时间、旅费和所需设备：1)开发持续的普查数据收集机制，以确定潜在的临床试验对象；2)培训和改善临床实验室的基础设施，以优化腹泻病例诊断测试、质量控制的微生物方法和不良事件评估的能力；3)与将包括在临床试验中的益生菌产品制造商进行讨论；4)从相关机构获得管理和人类受试者监测的协议，包括建立数据安全监测委员会和认证培训；5)为临床试验阶段建立标准操作程序(SOP)和文件程序；以及数据收集工具和定期分析程序，以及6)与社区建立对话，以建立对试验的支持并解决关切问题。在临床试验前的规划期内支持这些活动将极大地促进试验的实施。

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.