Omega-3 Fatty Acids for Prevention of Dry Eye Disease: VITAL-DED

描述（由申请人提供）：干眼病（DED）是美国老年人的一个重要和普遍的公共卫生问题，每年与近40亿美元的直接成本和550亿美元的间接成本相关。VITAL-DED旨在研究补充海洋omega-3脂肪酸（FA）预防DED的疗效，以及长期改善其相关的慢性眼表疼痛和生活质量影响，包括阅读和驾驶问题。该研究将利用维生素D和OmegA-3试验（VITAL, 1U01CA138962）的宝贵资源和数据，该试验是一项随机、双盲、安慰剂对照、2 × 2因子试验，旨在测试海洋OmegA-3 FA （465 mg/ D二十碳五烯酸+ 375 mg/ D二十二碳六烯酸）和维生素D3（胆钙化醇，2000 IU/ D）补充剂在2万名年龄分别为50岁和55岁的男性和女性中对癌症和心血管疾病的初级预防作用。从2011年7月开始，一直持续到2012年，愿意和符合条件的邀请邮件的受访者将参加一个月的磨合，随后，那些在磨合期间仍然愿意，符合条件和遵守的人将被随机分配到omega-3 FA或匹配的安慰剂和维生素D3或匹配的安慰剂。每隔1年，参与者将获得新的药丸供应和跟踪

DESCRIPTION (provided by applicant): Dry eye disease (DED) is an important and prevalent public health concern for older Americans that is associated with nearly $4 billion in direct and $55 billion in indirect costs annually. VITAL-DED proposes to study the efficacy of marine omega-3 fatty acid (FA) supplementation for the prevention of DED, as well as the long-term amelioration of its associated chronic ocular surface pain and quality of life impacts, which include problems reading and driving. The study will leverage invaluable resources and data from the VITamin D and OmegA-3 TriaL (VITAL, 1U01CA138962), a randomized, double-blind, placebo-controlled, 2x2 factorial trial to test marine omega-3 FA (465 mg/d eicosapentaenoic acid + 375 mg/d docosahexaenoic acid) and vitamin D3 (cholecalciferol, 2000 IU/d) supplements in the primary prevention of cancer and cardiovascular disease among 20,000 men and women aged >50 y & >55 y, respectively. Beginning in July 2011 and continuing throughout 2012, willing and eligible respondents to an invitational mailing will be enrolled in a month run-in, and subsequently those who remain willing, eligible, and compliant during the run-in will be randomly assigned to omega-3 FA or a matching placebo and vitamin D3 or a matching placebo. At 1-year intervals, participants will receive a new supply of pills and a follow up questionnaire on compliance, side effects, and incidence of health endpoints. We propose to ascertain prevalent (pre-randomization) and incident (post-randomization) DED endpoints in the VITAL trail. The primary Specific Aims of VITAL-DED are to test whether omega-3 FA supplementation: 1) reduces the incidence of DED, 2) improves the natural history of DED by relieving symptoms and other impacts on quality of life. Secondary Aims will estimate the incidence of DED in the US, prospectively examine the natural history of DED, explore factors that could modify or influence the impact of omega-3 FA supplementation, evaluate the inter-relationship of DED and depression, and test for possible independent or joint effects of vitamin D3 supplementation in the incidence and natural history of DED. This research is responsive to a program priority of the National Eye Institute's Strategic Plan to improve our understanding of and develop preventive strategies for inflammatory corneal and ocular surface diseases; and also addresses several issues identified in the recent 2010 NEI Workshop on Ocular Pain and Sensitivity. The hypotheses are supported by a compelling biological rationale and strong preliminary data from our prior epidemiological studies, as well as from laboratory investigations and small randomized trials, which suggest that omega-3 FA supplementation, could prevent DED and improve its natural history. We believe the timely start of VITAL-DED offers a unique but time-sensitive opportunity to obtain a reliable, efficient, and informative evaluation of the efficacy of the most promising preventive agent for DED. Given our success with prior large simple trials, our experience with DED, and our proposed methodology, we think VITAL-DED will provide definitive results to guide public health and clinical recommendations for DED prevention and management.