VITamin D and omegA-3 triaL (VITAL)

描述（由申请人提供）：我们建议进行一项大型、具有成本效益、随机、双盲、安慰剂对照、2x2因子试验，研究维生素D（以维生素D3[胆骨化醇]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]）补充剂在癌症和心血管疾病（CVD）的初级预防中的作用。来自实验室研究、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强烈表明，这些营养制剂可降低癌症或心血管疾病的风险，但缺乏在普通人群（即未选择疾病风险的人群）中进行适当剂量的大型一级预防试验。人们对补充维生素D和鱼油的热情日益高涨，这突显了在它们的使用变得如此普遍（通过补充和强化食品供应），以至于无法招募参与者和验证假设之前，及时启动这样一项试验的迫切需要。拟议的试验将在20 000名60岁的男子和65岁的妇女中进行，从120万人的邮寄中招募，包括卫生和其他专业人员、美国退休人员协会（以前称为美国退休人员协会）的成员和其他人。邮件将包含一封描述试验的信，一份知情同意书，以及一份调查问卷，询问过去的病史，癌症和血管风险因素，饮食，药物和营养补充剂的使用情况。自愿和符合条件的受访者将参加为期3个月的磨合期，在此期间他们将获得安慰剂。在试验结束时，那些仍然愿意且符合条件的人，以及那些报告服用了至少三分之二药片的人，将被随机分配到四个治疗组中的一个，为期5年：维生素D3 （1600 IU/d）和鱼油（EPA+DHA, 1 g/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和鱼油血液样本将被收集和储存，以评估基线25-羟基维生素D和omega-3脂肪酸水平的效果改变，以及未来对遗传/生化假设的辅助研究。每隔1年，参与者将获得新的药物供应，并对依从性、可能的副作用和终点发生率进行随访问卷调查。终点将通过医疗记录审查确认。鉴于我们之前基于邮件的大型简单试验和队列研究的成功，以及在预期源人群中进行的试点研究的结果，我们相信该试验将能够为研究假设提供明确的阳性结果或信息性的无效结果。

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.