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40亿美元的直接费用和550亿美元的间接费用有关。VITAL-DED计划研究海洋omega-3脂肪酸（FA）补充剂预防DED的功效，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 TriaL的宝贵资源和数据（VITAL，1U 01 CA 138962），一项随机、双盲、安慰剂对照、2x2析因试验，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20，000名年龄>50岁和>55岁的男性和女性中分别用于癌症和心血管疾病的初级预防。从2011年7月开始并持续到2012年，将在一个月的导入期内招募自愿且符合条件的邀请邮件应答者，随后将在导入期内保持自愿、符合条件和依从性的应答者随机分配至omega-3 FA或匹配的安慰剂和维生素D3或匹配的安慰剂组。每隔一年，参与者将获得一个新的药丸供应和后续 关于依从性、副作用和健康终点发生率的调查问卷。我们建议在VITAL试验中确定流行（随机化前）和事件（随机化后）DED终点。VITAL-DED的主要具体目的是测试omega-3 FA补充剂是否：1）降低DED的发病率，2）通过缓解症状和对生活质量的其他影响来改善DED的自然病程。次要目的将估计美国DED的发病率，前瞻性检查DED的自然史，探索可能改变或影响omega-3 FA补充剂影响的因素，评价DED和抑郁症的相互关系，并测试维生素D3补充剂在DED发病率和自然史中可能的独立或联合作用。这项研究是响应国家眼科研究所的战略计划，以提高我们的理解，并制定预防策略，炎症性角膜和眼表疾病的计划优先级;也解决了几个问题，在最近的2010年NEI眼疼痛和敏感性研讨会确定。这些假设得到了令人信服的生物学原理和来自我们先前流行病学研究以及实验室调查和小型随机试验的强有力的初步数据的支持，这些数据表明omega-3 FA补充剂可以预防DED并改善其自然史。我们认为，VITAL-DED的及时启动提供了一个独特但时间敏感的机会，可以对最有前途的DED预防剂的疗效进行可靠，有效和信息丰富的评估。鉴于我们在之前的大型简单试验中取得的成功，我们在DED方面的经验以及我们提出的方法，我们认为VITAL-DED将提供明确的结果，以指导DED预防和管理的公共卫生和临床建议。

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.