The VITamin D and OmegA-3 TriaL (VITAL)

描述(由申请人提供)：这是维生素D和omega-3试验(VITAL)的续展申请，该试验正在评估维生素D和海洋omega-3脂肪酸补充剂在癌症和心血管疾病(CVD)一级预防中的作用。关于这些制剂在预防癌症、心血管疾病和其他疾病中的作用的证据，关于因果关系仍然没有定论，也不足以提供初级预防的营养建议。在普通人群中缺乏适当设计的随机试验。为了填补这一知识空白，我们一直在进行VITAL，一项高度创新、成本效益高、大规模、随机、双盲、安慰剂对照的临床试验，在基线水平上没有癌症或心血管疾病的26,000名美国男性和女性中，他们只根据年龄(男性年龄为50岁，女性年龄为55岁)进行选择，黑人比例过高(Ne5000)。在2x2析因设计中，参与者被随机分为维生素D3(胆钙化醇，2000IU/d)和海洋omega-3脂肪酸(Omacor(R)鱼油，1g/d，含有二十碳五烯酸[EPA]+二十二碳六烯酸[DHA])补充剂(或安慰剂)。如果继续提供资金，中位数的治疗期将为5年。在第一个周期中，我们成功地达到或超过了我们的招募目标，招募了一个种族/民族多元化的队列，收集了16,000名参与者的基线血液/DNA样本(计划在6,000名参与者中进行后续抽血)，并在试验中对维生素D和omega-3脂肪酸的实验室分析进行了广泛的验证研究。年度跟踪调查问卷评估治疗依从性(通过部分参与者的血液样本确认)、副作用、终点发生情况以及癌症和血管风险因素。自我报告的终点是由对治疗分配视而不见的医生通过医疗记录审查确认的，死亡是通过国家死亡指数-Plus和其他来源确定的。我们存档的血液样本可以评估基线25-羟基维生素D和omega-3脂肪酸水平的效果修改，生物标记物随时间的变化，以及遗传/生化假说的测试。与我们的科学同事一起，我们已经获得了18项辅助研究的资金，以评估这些补充剂在预防其他慢性疾病(包括糖尿病、认知功能减退、抑郁症和自身免疫性疾病)中的作用，并建立了一个临床部分，用于对亚队列进行深入的表型分析(n=1000)。预计试验将为我们的初选提供最终的积极或信息性的无效结果 这是一项假设，并将成为研究维生素D和omega-3脂肪酸对健康影响的国家资源，并提供广泛合作的机会。这是一项高影响的试验，因为这些发现可能会对临床和公共卫生产生重大影响。

DESCRIPTION (provided by applicant): This is a renewal application for a 5-year continuation of the VITamin D and OmegA-3 TriaL (VITAL), which is evaluating the role of vitamin D and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease (CVD). Evidence for a role of these agents in preventing cancer, CVD, and other diseases remains inconclusive regarding causality and insufficient to inform nutritional recommendations for primary prevention. Appropriately designed randomized trials in general populations are lacking. To fill this knowledge gap, we have been conducting VITAL, a highly innovative, cost-efficient, large-scale, randomized, double-blind, placebo-controlled clinical tria among 26,000 U.S. men and women without cancer or CVD at baseline, who have been selected only on age (men aged e50 and women aged e55), with an oversampling of blacks (ne5000). In a 2x2 factorial design, participants have been randomized to vitamin D3 (cholecalciferol, 2000 IU/d) and marine omega-3 fatty acids (Omacor(R) fish oil, 1 g/d, containing eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements (or placebos) independently. Contingent on continued funding, the median treatment period will be 5 years. During the first cycle, we have successfully met or surpassed our recruitment goals, enrolled a racially/ethnically diverse cohort, collected baseline blood/DNA samples on >16,000 participants (with plans for follow-up bloods in 6000), and conducted extensive validation studies of the laboratory assays for vitamin D and omega-3 fatty acid measurements in the trial. Annual follow-up questionnaires assess treatment compliance (confirmed by blood samples in a subset of participants), side effects, endpoint occurrence, and cancer and vascular risk factors. Self-reported endpoints are confirmed by medical record review by physicians blinded to treatment assignment, and deaths are ascertained through the National Death Index-Plus and other sources. Our archived blood samples allow assessment of effect modification by baseline 25-hydroxyvitamin D and omega-3 fatty acid levels, changes in biomarkers over time, and testing of genetic/biochemical hypotheses. With our scientific colleagues, we have obtained funding for 18 ancillary studies to evaluate the role of these supplements in preventing other chronic diseases (including diabetes, cognitive decline, depression, and autoimmune disorders), and established an in-clinic component for in-depth phenotyping of a subcohort (n=1000). The trial is expected to provide either definitive positive or informative null results for our primary hypotheses and will serve as a national resource for research on the health effects of vitamin D and omega-3 fatty acids, with opportunities for extensive collaborations. This is a high-impact trial due to the potential for major clinical and public health implications of the findings.