VITAL-AMD: Prevention of AMD in the VITamin D and OmegA-3 Trial

描述（由申请人提供）：本申请拟研究维生素D3和海洋omega-3脂肪酸补充剂预防老年性黄斑变性（AMD）的功效，AMD是美国致盲的主要原因。该研究将利用维生素D和OmegA-3试验（VITAL）的宝贵资源和数据，这是一项随机、双盲、安慰剂对照、2 × 2因子试验，旨在测试维生素D（维生素D3[胆骨化醇]，2000 IU/ D）和海洋OmegA-3脂肪酸（二十碳五烯酸[EPA] +二十二碳六烯酸[DHA]， 1 g/ D）补充剂对癌症和心血管疾病的一级预防作用。美国国立卫生研究院(1 u01ca138962)是资金的主要重要的审判,将研究20000岁e60 y岁的男性和女性e65 y。自2010年10月开始,持续了整个2011年,愿意和合格的受访者邀请赛邮寄美元将参加三个月的争执,随后那些仍然愿意并有资格,并报告了至少三分之二的研究药物,将随机分配到1的4 5年治疗组:维生素D3 （2000 IU/d）和鱼油（EPA+DHA, 1 g/d）；维生素D3和鱼油安慰剂；维生素D3安慰剂和鱼油；维生素D3安慰剂和鱼油安慰剂每隔1年，参与者将获得新的药物供应，并对依从性、可能的副作用和终点发生率进行随访问卷调查。我们建议在VITAL队列中确定AMD的流行和发生终点，以研究维生素D3和鱼油在AMD预防中的功效。本辅助研究的主要目的是测试：1)补充鱼油（EPA+DHA, 1g/d）是否可以减少AMD的发生和进展，以及2)补充维生素D3 （2000 IU/d）是否可以减少AMD的发生和进展。Secondary Aims将测试维生素D3和鱼油的协同或拮抗作用，以及维生素D3和鱼油的相互作用

DESCRIPTION (provided by applicant): This application proposes to study the efficacy of vitamin D3 and marine omega-3 fatty acid supplementation for prevention of age-related macular degeneration (AMD), the leading cause of blindness in the US. The study will leverage invaluable resources and data from the VITamin D and OmegA-3 TriaL (VITAL), a randomized, double-blind, placebo-controlled, 2x2 factorial trial designed to test vitamin D (vitamin D3 [cholecalciferol], 2000 IU/d) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1 g/d) supplements in the primary prevention of cancer and cardiovascular disease. The National Institutes of Health (1U01CA138962) is funding the main VITAL trial, which will study 20,000 men aged e60 y and women aged $ e65 y. Beginning in October 2010 and continuing throughout 2011, willing and eligible respondents to an $ invitational mailing will be enrolled in a 3-month run-in, and subsequently those who remain willing and eligible, and who report having taken at least two-thirds of study pills, will be randomly assigned to 1 of 4 treatment groups for 5 years: vitamin D3 (2000 IU/d) and fish oil (EPA+DHA, 1 g/d); vitamin D3 and fish oil placebo; vitamin D3 placebo and fish oil; and vitamin D3 placebo and fish oil placebo. At 1-year intervals, participants will receive a new supply of pills and a follow-up questionnaire on compliance, possible side effects, and incidence of endpoints. We propose to ascertain prevalent and incident AMD endpoints in the VITAL cohort in order to study the efficacy of vitamin D3 and fish oil in AMD prevention. The Primary Aims of this ancillary study are to test whether: 1) fish oil supplementation (EPA+DHA, 1g/d) reduces the incidence and progression of AMD and whether 2) vitamin D3 supplementation (2000 IU/d) reduces the incidence and progression of AMD. Secondary Aims will test for synergistic or antagonistic effects of vitamin D3 and fish oil, as well as interactions of vitamin D3 and fish oil with common AMD-associated genetic polymorphisms, and polymorphisms related to pathways involved in vitamin D3 or omega-3 fatty acid metabolic activity. This research is responsive to a program priority of the National Eye Institute's Strategic Plan to develop new treatments for AMD. We believe the timely start of the proposed AMD ancillary to the VITAL trial offers a unique but time-sensitive opportunity to obtain a reliable, efficient, and informative evaluation o the efficacy of two extremely promising preventive agents for AMD at a fraction of the cost of separate trials. Given our success with prior mail-based, large, simple trials and cohort studies, our experience with AMD, and our proposed methodology, we believe the trial will be able to provide either definitive positive or informative null results regarding the study hypotheses.