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

该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 预防白内障和年龄相关性黄斑变性（AMD），这是视力受损的两个主要原因 在美国成年人。最近的发现来自医生的健康研究II，这是唯一的大规模临床试验， 复合维生素，表明白内障的显着减少，但升高，虽然统计学上不显着， 增加AMD的风险。这些在男性中的发现需要在其他男性中得到证实，并扩展到女性。的 拟议中的研究将利用可可补充剂和多学科成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， 可可提取物补充剂（Mars Symbioscience）和Centrum银复合维生素（Pfizer）预防 在12，000名年龄≥65岁的女性和6，000名年龄≥60岁的男性中， 4年的治疗和随访。妇女参与者将从妇女健康倡议中挑选 队列，男性受试者将从筛选参与的目标人群中抽取（但不 随机化）的维生素D和OmegA-3 TriaL（VITAL）。从2015年6月开始，持续到 2016年，将在3个月的磨合期内招募有意愿和符合条件的邀请邮件受访者。的人 在导入期表现出良好的服药依从性，并保持意愿和合格，将被随机 分配至4个治疗组之一，持续5年。每隔一年，参与者将获得一个新的供应， 药丸和关于依从性、可能的副作用和终点发生率的随访问卷。我们 建议记录COSMOS队列中的偶发白内障和流行和偶发AMD终点， 评价多种维生素和可可提取物补充剂预防白内障和AMD的有效性。 这项拟议研究的主要目的是测试1）每日服用多种维生素是否会降低以下风险 白内障; 2）每日多种维生素将降低总AMD事件的风险，即AMD事件加上 进展为晚期AMD（新生血管性AMD+中央地图状萎缩）的病例， 基线时患有AMD的受试者。可可提取物补充剂的效果（胶囊含750 黄烷醇类，包括75 mg（-）-表儿茶素和90 mg可可碱）降低AMD和白内障风险 将作为次要目标进行研究。这项研究是响应国家眼睛的计划优先事项 研究所的战略计划，以改善诊断，治疗和预防眼病。我们相信 COSMOS辅助的拟议眼病提供了一个独特的机会，以获得可靠，有效， 两种非常有前途的预防剂对白内障和AMD的有效性的信息评估， 单独审判费用的一小部分。

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.