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

描述（由申请人提供）：本申请旨在研究维生素D3和海洋ω-3脂肪酸补充剂预防年龄相关性黄斑变性（AMD）的疗效，AMD是美国致盲的主要原因。这项研究将利用维生素D和OmegA-3 TriaL（VITAL）的宝贵资源和数据，这是一项随机、双盲、安慰剂对照、2x2析因试验，旨在测试维生素D（维生素D3 [胆钙化醇]，2000 IU/d）和海洋ω-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，用于癌症和心血管疾病的初级预防。美国国立卫生研究院（1U01CA138962）正在资助主要的VITAL试验，该试验将研究20，000名年龄为60岁的男性和年龄为65岁的女性。从2010年10月开始并持续到2011年，将在3个月的导入期内招募愿意和符合条件的$邀请邮件应答者，随后将那些仍然愿意和符合条件且报告已服用至少三分之二研究药物的应答者随机分配至4个治疗组之一，持续5年：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;以及维生素D3安慰剂和鱼油安慰剂。每隔一年，参与者将收到一份新的药丸供应和一份关于依从性、可能的副作用和终点发生率的随访问卷。我们建议在VITAL队列中确定AMD的流行和偶发终点，以研究维生素D3和鱼油预防AMD的疗效。这项辅助研究的主要目的是测试：1）鱼油补充剂（EPA + DHA，1g/d）是否降低AMD的发病率和进展，以及2）维生素D3补充剂（2000 IU/d）是否降低AMD的发病率和进展。次要目的将测试维生素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 与常见的AMD相关的遗传多态性，以及与维生素D3或ω-3脂肪酸代谢活性相关的途径的多态性。这项研究是响应国家眼科研究所战略计划的一个优先项目，以开发AMD的新治疗方法。我们认为，VITAL试验的拟议AMD辅助试验的及时启动提供了一个独特但时间敏感的机会，可以以单独试验成本的一小部分获得两种非常有前途的AMD预防药物疗效的可靠、有效和信息丰富的评价。鉴于我们在之前基于邮件的大型简单试验和队列研究中的成功，我们对AMD的经验以及我们提出的方法，我们相信该试验将能够提供关于研究假设的明确的阳性或信息性无效结果。 公共卫生相关性：维生素D和ω-3脂肪酸的健康益处在医学文献和大众媒体中越来越受到关注。然而，缺乏关于这些药物的健康益处和风险的确切数据。这项大型临床试验的结果将阐明维生素D和omega-3脂肪酸补充剂在预防AMD中的作用，AMD是美国男性和女性失明的主要原因。

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. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D and omega-3 fatty acids are receiving increasing attention in the medical literature and the popular press. However, definitive data on health benefits and risks of these agents are lacking. Findings from this large clinical trial will clarify the role of vitamin D and omega-3 fatty acid supplements in he prevention of AMD, the leading cause of blindness in US men and women.