VITamin D and omegA-3 triaL (VITAL)

描述(申请人提供)：我们建议进行一项大型、成本效益高、随机、双盲、安慰剂对照的2x2因素试验，将维生素D(以维生素D3[胆钙化醇]的形式)和海洋omega-3脂肪酸(二十碳五烯酸[EPA]+二十二碳六烯酸[DHA])补充剂用于癌症和心血管疾病(CVD)的一级预防。实验室研究、流行病学研究、小型一级预防试验和/或大型二级预防试验的数据有力地表明，这些营养剂降低了癌症或心血管疾病的风险，但缺乏在普通人群中具有足够剂量的大型一级预防试验(即，未根据疾病风险进行选择)。人们对补充维生素D和鱼油的热情日益高涨，突显出迫切需要在它们的使用变得如此普遍(通过补充和强化食品供应)使参与者招募和假设检验变得不可能之前，及时启动这种试验。拟议的试验将在20,000名年龄为60岁的男性和20,000名年龄为65岁的女性中进行，将从邮寄给120万人的邮件中招募，其中包括卫生和其他专业人员、美国退休人员协会(美国退休人员协会)成员和其他人。邮寄将包含一封描述试验的信，一份知情同意书，以及一份问卷，征求有关过去病史、癌症和血管风险因素、饮食以及药物和营养补充剂使用情况的信息。有意愿和符合条件的受访者将参加为期3个月的试运行，在此期间他们将获得安慰剂。在磨合结束时，那些仍然愿意并符合条件的人，以及那些报告至少服用了三分之二的药片的人，将被随机分配到四个治疗组中的一个，为期5年：维生素D3(1600IU/d)和鱼油(EPA+DHA，1g/d)；维生素D3和鱼油安慰剂；安慰剂维生素D3和鱼油；以及安慰剂维生素D3和安慰剂鱼油。将收集和储存血液样本，以便通过基线25-羟基维生素D和omega-3脂肪酸水平以及未来对遗传/生化假说的辅助研究来评估效果修改。每隔一年，参与者将收到一份新的药物供应和一份关于依从性、可能的副作用和终点发生率的后续问卷。终端将通过病历审查进行确认。鉴于我们之前在基于邮件的大型简单试验和队列研究中的成功，以及在目标来源人群中进行的试点研究的结果，我们相信试验将能够提供关于研究假设的确凿的、积极的或信息性的无效结果。与公共健康相关：维生素D和海洋omega-3脂肪酸的所谓健康益处正在医学文献和流行媒体中受到越来越多的关注。然而，缺乏关于这些制剂的健康益处和风险的明确数据。这项大型临床试验的结果将阐明维生素D和海洋omega-3脂肪酸补充剂在男性和女性癌症和心血管疾病一级预防中的作用。

DESCRIPTION (provided by applicant): We propose to conduct a large, cost-effective, randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements in the primary prevention of cancer and cardiovascular disease (CVD). Data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials strongly suggest that these nutritional agents reduce cancer or CVD risk, but large primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. Growing enthusiasm for supplemental vitamin D and fish oil underscores the urgent need for a timely initiation of such a trial, before their use becomes so prevalent (through supplements and fortification of the food supply) as to render participant recruitment and hypothesis testing impossible. The proposed trial will be conducted among 20,000 men aged e60 and women aged e65, to be recruited from a mailing to 1.2 million persons, including health and other professionals, members of AARP (formerly known as the American Association of Retired Persons), and others. The mailing will contain a letter describing the trial, an informed consent form, and a questionnaire soliciting information on past medical history, cancer and vascular risk factors, diet, and medication and nutritional supplement use. Willing and eligible respondents will be enrolled in a 3-month run-in, during which they will receive placebos. At the end of the run-in, those who remain willing and eligible, and who report having taken at least two-thirds of the pills, will be randomly assigned to one of four treatment groups for 5 years: vitamin D3 (1600 IU/d) and fish oil (EPA+DHA, 1 g/d); vitamin D3 and fish oil placebo; placebo vitamin D3 and fish oil; and placebo vitamin D3 and placebo fish oil. Blood samples will be collected and stored to allow assessment of effect modification by baseline 25-hydroxyvitamin D and omega-3 fatty acid levels, as well as future ancillary studies of genetic/biochemical hypotheses. 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. Endpoints will be confirmed by medical record review. Given our success with prior mail-based large simple trials and cohort studies, as well as results of a pilot study in the intended source population, we believe the trial will be able to provide either definitive positive or informative null results regarding the study hypotheses. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D and marine omega-3 fatty acids are receiving increasing attention in the medical literature and the popular press. However, definitive data on health benefits and risks of these agents are lacking. Findings from this large clinical trial will clarify the role of vitamin D and marine omega-3 fatty acid supplements in the primary prevention of cancer and cardiovascular disease in men and women.