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

VITAL-AMD：维生素 D 和 OmegA-3 试验中预防 AMD

• 批准号: 8728867
• 负责人: WILLIAM G CHRISTEN
• 金额: $ 77.68万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8728867
• 关键词: Address; Adverse effects; Age; Age related macular degeneration; Ancillary Study; Angiogenesis Inhibitors; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Attention; Benefits and Risks; Blindness; Blood specimen; Cardiovascular Diseases; Cholecalciferol; Clinical; Clinical Trials; Clinical Trials Design; Cohort Studies; Complement Factor H; Data; Docosahexaenoic Acids; Double-Blind Method; Eicosapentaenoic Acid; Elderly; Enrollment; Evaluation; Exudative age-related macular degeneration; Fatty Acids; Fish Oils; Funding; Gene-Modified; Genes; Genetic Polymorphism; Guidelines; Health Benefit; Incidence; Literature; Mails; Marines; Medical; Metabolic; Methodology; National Eye Institute; Omega-3 Fatty Acids; Participant; Pathway interactions; Patients; Placebo Control; Placebos; Prevention; Preventive; Primary Cancer Prevention; Primary Prevention; Property; Public Health; Questionnaires; RORA gene; Randomized; Reducing Agents; Reporting; Research; Resources; Respondent; Risk; Role; Running; Sampling; Secondary Prevention; Staging; Strategic Planning; Subgroup; Supplementation; Testing; Time; United States National Institutes of Health; Vascular Endothelial Growth Factors; Visual Acuity; Vitamin D; Vitamin D3 Receptor; Woman; Zinc; advanced disease; aged; base; case control; cohort; cost; cost effective; desaturase; design; efficacy testing; experience; follow-up; geographic atrophy; innovation; men; older men; older women; pill; programs; public health relevance; sex; success

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.

描述（由申请人提供）：本申请拟研究维生素 D3 和海洋 omega-3 脂肪酸补充剂预防年龄相关性黄斑变性 (AMD) 的功效，AMD 是美国失明的主要原因。该研究将利用维生素 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 omega-3 脂肪酸（二十碳五烯酸 [EPA] + 二十二碳六烯酸 [DHA]，1 g/d) 癌症和心血管疾病一级预防的补充剂。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 60 岁以下的男性和 65 岁以下的女性。从 2010 年 10 月开始，一直持续到 2011 年，愿意并符合资格的 $ 邀请函的受访者将参加为期 3 个月的磨合期，随后那些仍愿意且符合资格并报告已参加至少三分之二的人将参加为期 3 个月的磨合期。研究药丸，将被随机分配到 4 个治疗组中的 1 个，持续 5 年：维生素 D3（2000 IU/天）和鱼油（EPA+DHA，1 克/天）；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和一份关于依从性、可能的副作用和终点发生率的后续调查问卷。我们建议确定 VITAL 队列中常见和事件性 AMD 终点，以便研究维生素 D3 和鱼油在预防 AMD 中的功效。这项辅助研究的主要目的是测试：1) 补充鱼油（EPA+DHA，1g/天）是否可以降低 AMD 的发病率和进展，以及 2) 补充维生素 D3（2000 IU/天）是否可以降低 AMD 的发病率和进展？ AMD 的进展。次要目标将测试维生素 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 AMD 相关遗传多态性，以及与维生素 D3 或 omega-3 脂肪酸代谢活性相关途径相关的多态性。这项研究响应了国家眼科研究所战略计划的优先项目，即开发针对 AMD 的新疗法。我们相信，及时启动拟议的 VITAL 试验辅助 AMD 提供了一个独特但时间敏感的机会，可以获得可靠、高效和信息丰富的评估，以评估两种极具前景的 AMD 预防药物的功效，而成本仅为单独的试验。鉴于我们之前基于邮件的大型简单试验和队列研究的成功、我们在 AMD 方面的经验以及我们提出的方法，我们相信该试验将能够提供有关研究假设的明确的阳性结果或信息性无效结果。