Case-Control Studies Nested in National ALS Registry to Evaluate Environmental Risks

国家 ALS 登记处的病例对照研究用于评估环境风险

• 批准号: 9045228
• 负责人: HIROSHI MITSUMOTO
• 金额: $ 39.88万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9045228
• 关键词: Case; Control; Studies; Nested; National

 DESCRIPTION (provided by applicant): Amyotrophic lateral sclerosis (ALS) is considered the most devastating neurodegenerative disease. Patients suffer progressive functional loss, including loss of speech, swallowing, mobility, and respiration that leads to death on average 2 to 4 years after diagnosis. Except for aggressive symptomatic care, there are no effective treatments. More than 50 clinical trials based on plausible hypotheses of disease mechanisms have failed except for riluzole. Identified inherited pathogenic mutations account for ~10% of all ALS cases; the cause of most sporadic cases is unknown. ALS is now considered to be potentially caused by a combination of both genetic and environmental risk factors. Our overall hypothesis is that individual environmental risk factors reported to be associated with ALS act via a common mechanism, specifically oxidative stress (OS). Our NIEHS-funded prospective multicenter cohort study of ALS (ALS COSMOS), which investigates the extent to which multiple risk factors associated with OS are also associated with ALS progression, is in its final stages. Our current ARREST ALS project expands ALS COSMOS at a national level through the National ALS Registry, using structured telephone interviews and one-time urine and saliva collection. Now, we propose a set of well-designed, high-quality, case-control studies nested within ARREST ALS. We specifically aim: 1. To evaluate environmental and other risk factors in a population-based case-control study nested within the ARREST ALS study of the National ALS Registry. The cases (150 patients) will be identified in the on- going ARREST ALS project. We will match 2 controls to each case based on sex, age (± 5 years), race/ethnicity, and geographic area of residence. We will administer our well-validated, structured interview to determine cognitive function and obtain data on early life events and environmental, residential, occupational, dietary, lifestyle, and psychological factors. Dietary questionnaire data, first-void urine samples to measure OS markers, and saliva DNA will be collected; 2. To evaluate early life and late life environmental and other risk factors in a sibling-based, case-control study. We will identify a same-sex sibling who agrees to participate and is closest in age to the case. We estimate that 80% of cases will have a sibling who meets these criteria. They will receive the same risk factor assessment and provide saliva and urine samples as the population controls. 3. To evaluate individual or aggregate environmental risk factors between cases and controls at different stages of life and to investigate the significance of the urinary OS biomarker in relation to ALS and environmental risk factors. We will analyze risk factors at different stages of life in the two control groups combined in comparison to the cases and further analyze OS biomarkers in relation to risk factors. In summary, carefully designed population-based and sibling-based case-control studies nested within ARREST ALS will reveal entirely new and unique data concerning environmental risk factors, disease progression, and the potential cause(s) of ALS.

 描述（由适用提供）：肌萎缩性侧索硬化症（ALS）被认为是最毁灭性的神经退行性疾病。患者遭受进行性功能丧失，包括言语丧失，吞咽，流动性和呼吸，诊断后平均2至4年导致死亡。除了积极的症状护理外，没有有效的治疗方法。除Riluzole以外，基于疾病机制的合理假设的50多个临床试验失败了。确定的遗传病原突变占所有ALS病例的约10％；大多数零星病例的原因尚不清楚。现在，ALS被认为是由于遗传和环境风险因素的结合而可能引起的。我们的总体假设是，据报道，各个环境风险因素通过共同的机制，特别是氧化应激（OS）相关。我们的NIEHS资助的ALS（ALS Cosmos）的前瞻性多中心队列研究研究了与ALS进展相关的多个风险因素在多大程度上与ALS进展相关的程度。我们目前的逮捕ALS项目使用结构化电话采访以及一次性尿液和唾液收集，通过国家ALS注册表在国家一级扩展ALS Cosmos。现在，我们提出了一组精心设计的高质量，案例对照研究，这些研究嵌套在ALS中。我们具体目的：1。评估嵌套在国家ALS注册中心逮捕ALS研究中的基于人群的病例对照研究中的环境和其他危险因素。将在“逮捕ALS”项目中确定病例（150名患者）。我们将根据性别，年龄（±5岁），种族/种族和居住地理区域将2个对照与每个案例进行匹配。我们将管理经过良好的结构化访谈，以确定认知功能，并获取有关早期生活事件和环境，居民，住宅，饮食，生活方式和心理因素的数据。将收集饮食问卷数据，第一个尿液样品，以测量OS标记和唾液DNA； 2。在基于同胞的病例对照研究中评估早期生活和晚期环境和其他风险因素。我们将确定同意参加并在此案年龄关闭的同性兄弟姐妹。我们估计80％的案件将有一个符合这些标准的兄弟姐妹。他们将获得相同的风险因素评估，并提供与人口控制的唾液和尿液样本。 3。评估案例和对照在不同阶段的案例和对照之间的个人或总体环境风险因素，并研究与ALS和环境风险因素有关的尿OS生物标志物的重要性。我们将在两个对照组的生活阶段分析与案例相比，与危险因素相关的OS生物标志物的危险因素。总而言之，嵌套在ALS内的精心设计的基于人群和兄弟姐妹的病例对照研究将揭示有关环境风险因素，疾病进展以及ALS的潜在原因的全新和独特的数据。