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
基本信息
- 批准号:9045228
- 负责人:
- 金额:$ 39.88万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 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:
- 关键词:
项目摘要
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(由申请人提供):肌萎缩侧索硬化症(ALS)被认为是最具破坏性的神经退行性疾病。患者遭受进行性功能丧失,包括言语、吞咽、移动和呼吸的丧失,导致诊断后平均2至4年死亡。除了积极的对症治疗外,没有有效的治疗方法。除了利鲁唑之外,50多项基于疾病机制合理假设的临床试验都失败了。已确定的遗传性致病突变占所有ALS病例的约10%;大多数散发病例的原因尚不清楚。ALS现在被认为是由遗传和环境风险因素共同引起的。我们的总体假设是,据报道与ALS相关的个别环境风险因素通过共同机制起作用,特别是氧化应激(OS)。我们的NIEHS资助的ALS前瞻性多中心队列研究(ALS COSMOS),调查了与OS相关的多种风险因素与ALS进展相关的程度,已进入最后阶段。我们目前的ARREST ALS项目通过国家ALS登记处在国家一级扩展ALS COSMOS,使用结构化电话采访和一次性尿液和唾液收集。现在,我们提出了一套精心设计的,高质量的,病例对照研究嵌套在ARREST ALS。我们的具体目标是:1。在国家ALS登记处ARREST ALS研究中嵌套的基于人群的病例对照研究中评估环境和其他风险因素。这些病例(150例患者)将在正在进行的ARREST ALS项目中确定。我们将根据性别、年龄(± 5岁)、人种/种族和居住地理区域为每例病例匹配2例对照。我们将管理我们经过验证的结构化访谈,以确定认知功能,并获得有关早期生活事件和环境,居住,职业,饮食,生活方式和心理因素的数据。将收集饮食问卷数据、测量OS标志物的首次排尿样本和唾液DNA; 2.在一项以同胞为基础的病例对照研究中评估生命早期和生命晚期的环境和其他危险因素。我们将确定一个同意参与并且年龄与案件最接近的同性兄弟姐妹。我们估计80%的病例会有一个符合这些标准的兄弟姐妹。他们将接受与人群对照相同的风险因素评估,并提供唾液和尿液样本。3.评估不同生命阶段病例和对照之间的个体或总体环境风险因素,并研究尿OS生物标志物与ALS和环境风险因素相关的意义。我们将结合病例分析两个对照组中不同生命阶段的风险因素,并进一步分析与风险因素相关的OS生物标志物。总之,精心设计的基于人群和基于同胞的病例对照研究嵌套在ARREST ALS中,将揭示有关环境风险因素,疾病进展和ALS潜在原因的全新和独特的数据。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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HIROSHI MITSUMOTO其他文献
HIROSHI MITSUMOTO的其他文献
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{{ truncateString('HIROSHI MITSUMOTO', 18)}}的其他基金
Promoting Research in PLS: Current Knowledge and Future Challenges
促进 PLS 研究:当前知识和未来挑战
- 批准号:
9756640 - 财政年份:2019
- 资助金额:
$ 39.88万 - 项目类别:
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:
9321613 - 财政年份:2015
- 资助金额:
$ 39.88万 - 项目类别:
NIH ALS Conference: Clinical Research to Find the Pathogenesis and Cause of ALS
NIH ALS 会议:寻找 ALS 发病机制和原因的临床研究
- 批准号:
8129353 - 财政年份:2011
- 资助金额:
$ 39.88万 - 项目类别:
Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
氧化应激和疾病进展的多中心 ALS 队列研究
- 批准号:
8463181 - 财政年份:2009
- 资助金额:
$ 39.88万 - 项目类别:
Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
氧化应激和疾病进展的多中心 ALS 队列研究
- 批准号:
8070075 - 财政年份:2009
- 资助金额:
$ 39.88万 - 项目类别:
Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
氧化应激和疾病进展的多中心 ALS 队列研究
- 批准号:
8065999 - 财政年份:2009
- 资助金额:
$ 39.88万 - 项目类别:
Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
氧化应激和疾病进展的多中心 ALS 队列研究
- 批准号:
7727882 - 财政年份:2009
- 资助金额:
$ 39.88万 - 项目类别:
Multicenter ALS Cohort Study of Oxidative Stress and Disease Progression
氧化应激和疾病进展的多中心 ALS 队列研究
- 批准号:
8274459 - 财政年份:2009
- 资助金额:
$ 39.88万 - 项目类别:
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