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

描述(申请人提供)：本申请建议研究维生素D3和海洋omega-3脂肪酸补充剂对预防老年性黄斑变性(AMD)的疗效，AMD是美国的主要失明原因。这项研究将利用来自维生素D和omega-3试验(VITAL)的宝贵资源和数据，这是一项随机、双盲、安慰剂对照的2x2因子试验，旨在测试维生素D(维生素D3[胆钙醇]，2000IU/d)和海洋omega-3脂肪酸(二十碳五烯酸[EPA]二十二碳六烯酸[DHA]，1g/d)补充剂在癌症和心血管疾病的一级预防中的作用。美国国立卫生研究院(1U01CA138962)资助了这项主要的重要试验，该试验将研究20,000名60岁的男性和20,000名年龄65岁的女性。从2010年10月开始，持续到2011年，愿意并符合条件的受访者将参加为期3个月的初试，随后那些仍然愿意并符合条件的人将被随机分配到4组治疗中的1组，为期5年：维生素D3(2000IU/d)和鱼油(EPA DHA，1g/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。每隔一年，参与者将收到一份新的药物供应和一份关于依从性、可能的副作用和终点发生率的后续问卷。我们建议确定AMD在重要队列中的流行和发病终点，以研究维生素D3和鱼油在AMD预防中的效果。这项辅助研究的主要目的是测试：1)补充鱼油(EPA DHA，1g/d)是否降低AMD的发病率和进展；2)补充维生素D3(2000IU/d)是否降低AMD的发病率和进展。二级目标将测试维生素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 具有常见的与AMD相关的遗传多态，以及与维生素D3或omega-3脂肪酸代谢活动相关的途径的多态。这项研究是对国家眼科研究所开发AMD新疗法的战略计划的优先项目的响应。我们相信，作为VITAL试验辅助的拟议AMD的及时启动提供了一个独特但时间敏感的机会，可以以单独试验的一小部分费用，对两种极有希望的AMD预防药物的疗效进行可靠、有效和信息丰富的评估。鉴于我们之前在邮寄、大型、简单试验和队列研究方面的成功，我们在AMD方面的经验，以及我们建议的方法，我们相信试验将能够提供关于研究假设的确凿的积极或信息性的无效结果。

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.