COSMOS Eye: Cataract and AMD in a Trial of a Multivitamin and Cocoa Extract

这项修订后的申请建议研究多种维生素和可可提取物补充剂在 预防白内障和老年性黄斑变性(AMD)，这是导致视力障碍的两个主要原因 在美国成年人身上。医生健康研究II的最新发现，这是每日唯一的大规模临床试验 复合维生素，表明白内障显著减少，但升高，尽管在统计上没有显著意义， 患AMD的风险增加。这些在男性身上的发现需要在其他男性身上得到证实，并推广到女性身上。这个 拟议的研究将利用可可补充剂和多种维生素结果研究的资源和数据 (COSMOS)，一项随机、双盲、安慰剂对照、2x2析因试验，测试一项获得专利的高质量 可可提取物补充剂(玛氏共生)和Centrum Silver复合维生素(辉瑞)预防糖尿病 ≥65岁的12,000名女性和60岁的6,000名男性的心血管疾病和癌症 4年的治疗和随访。女性参与者将来自妇女健康倡议(WHI) 队列，男性参与者将从经过筛选的目标人群中挑选出来(但不是 随机)在维生素D和omega-3试验(VITAL)中。从2015年6月开始，一直持续到 2016年，愿意和符合条件的应聘者将参加为期3个月的试运行。那些 在磨合过程中表现出良好的服药依从性，并保持意愿和资格，将随机进行 分配到4个治疗组中的1个，为期5年。每隔一年，参与者将获得新的 以及关于依从性、可能的副作用和终点发生率的跟踪调查问卷。我们 建议在#年记录突发白内障和AMD的流行和突发AMD终点 目的评价复合维生素和可可提取物补充剂在预防老年性黄斑变性和白内障中的作用。 这项拟议的研究的主要目的是测试1)每天服用多种维生素是否会降低患糖尿病的风险 白内障；2)每天服用复合维生素将降低AMD事件的总风险，这是AMD事件加上AMD事件的组合 进展为晚期AMD(新生血管性AMD合并中心性地理萎缩)的病例中 基线时患有AMD的受试者。可可提取物补充剂(750粒胶囊)的效果 黄烷醇，包括75毫克(-)-表儿茶素和90毫克可可碱)，可降低患AMD和白内障的风险 将被视为次要目标。这项研究是对《国家之眼》节目的优先考虑 该研究所改进眼病诊断、治疗和预防的战略计划。我们相信 提议的附属于COSMOS的眼病提供了一个独特的机会，以获得可靠、有效和 对两种极有希望的白内障和AMD预防药物的疗效进行信息性评估 单独试验费用的一小部分。

This revised application proposes to study the efficacy of a multivitamin and cocoa extract supplementation in prevention of cataract and age-related macular degeneration (AMD), two leading causes of visual impairment in US adults. Recent findings from the Physicians’ Health Study II, the only large-scale clinical trial of a daily multivitamin, indicated a significant reduction in cataract, but an elevated, though statistically non-significant, increased risk of AMD. These findings in men require confirmation in other men and extension to women. The proposed study will utilize resources and data from the COcoa-Supplement and Multivitamins Outcomes Study (COSMOS), a randomized, double-blind, placebo-controlled, 2x2 factorial trial testing a patented, high-quality cocoa extract supplement (Mars Symbioscience) and Centrum Silver multivitamin (Pfizer) in the prevention of cardiovascular disease and cancer among 12,000 women aged ≥65 years and 6,000 men aged ≥60 years with 4 years of treatment and follow-up. Woman participants will be drawn from the Women’s Health Initiative (WHI) cohort, and male participants will be drawn from a target population screened for participation (but not randomized) in the VITamin D and OmegA-3 TriaL (VITAL). Beginning in June, 2015 and continuing through 2016, willing and eligible respondents to an invitational mailing will be enrolled in a 3-month run-in. Those who demonstrate good compliance with pill taking during the run-in, and remain willing and eligible, will be randomly assigned to 1 of 4 treatment groups for 5 years. 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 document incident cataract and prevalent and incident AMD endpoints in the COSMOS cohort in order to evaluate the efficacy of multivitamin and cocoa extract supplements in cataract and AMD prevention. The primary aims of the proposed study are to test whether 1) a daily multivitamin will reduce the risk of cataract; 2) a daily multivitamin will reduce the risk of total AMD events, a composite of incident AMD plus cases of progression to advanced AMD (neovascular AMD plus central geographic atrophy) among participants with prevalent AMD at baseline. The effect of cocoa extract supplements (capsule containing 750 mg/d flavanols, including 75 mg (-)-epicatechin, and 90 mg theobromine) in reducing risks of AMD and cataract will be examined as secondary aims. This research is responsive to a program priority of the National Eye Institute’s Strategic Plan to improve diagnosis, treatment, and prevention of eye disease. We believe the proposed eye disease ancillary to COSMOS offers a unique opportunity to obtain a reliable, efficient, and informative evaluation of the efficacy of two extremely promising preventive agents for cataract and AMD at a fraction of the cost of separate trials.