A Large Randomized Trial of Vitamin D, Omega-3 Fatty Acids and Cognitive Decline

描述(申请人提供)：VITAL(维生素D和omega-3试验)研究最近获得资助(2010年1月开始招募)，以调查维生素D和海洋omega-3脂肪酸补充剂对心血管疾病和癌症的一级预防作用。我们建议在3000名65岁以上的参与者中发起一项认知衰退的子研究，其中包括1000名非裔美国人。这是一个令人兴奋的机会，可以进行一项大规模、高成本效益的随机、双盲、安慰剂对照的2x2因素试验，研究维生素D(维生素D3[胆钙醇]，每天2000 IU)和海洋欧米伽-3脂肪酸(二十二碳六烯酸+二十碳五烯酸，每天1000毫克)补充剂对减缓认知能力下降的作用。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表明，这些营养剂可能会减少认知能力下降，但在一般健康的老龄化人口中缺乏大型试验。公众对补充维生素D和鱼油的热情日益高涨，突显出在它们的使用变得足够普遍(通过补充剂和食品强化)之前，迫切需要及时启动这种试验。重要的参与者将通过邮寄从普通人群中招募，包括卫生和其他专业人员、美国退休人员协会成员、Essence杂志订阅者和其他人；非洲裔美国人将被过度抽样，因为他们维生素D缺乏症的患病率更高。受访者将参加为期3个月的安慰剂磨合阶段，以测试参与程度。我们建议在磨合期进行基线电话认知测试，允许进行预随机化评估。电话认知电池将包括一般认知、言语记忆和执行功能的7项测试(我们在电话认知测试方面有丰富的经验，该电池将通过面对面认知测试在300名生命相关参与者中进行验证)。在磨合结束时，那些仍然愿意和符合条件并且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4.5年。将采集血液样本，以通过基线25-羟基维生素D、omega-3脂肪酸水平以及载脂蛋白E4状态来评估效果改善。每隔一年，参与者将收到新的药片供应和关于依从性、可能的副作用和病史的后续问卷。每隔1.5到2年，生命齿参与者将接受后续的认知功能评估，在4.5年内总共进行3次评估；下降最严重的第10个百分位数的参与者还将接受使用痴呆症问卷的电话线人访谈。鉴于我们之前在多个试验环境中进行的基于电话的认知功能评估的成功，我们相信VITAL-COG将能够提供关于研究假设的明确结果。为了完成认知功能的随机化前评估，VITAL-COG必须与定于2010年4月开始的父母试验(1 U01 CA138962)的安慰剂磨合期同时进行。 公共卫生相关性：鉴于人口老龄化的预测，在老年期间保持认知功能具有重大的公共卫生重要性，早期干预可能是最有效的。VITAL(维生素D和omega-3试验)研究最近获得资助，将于2010年1月开始招募，以调查维生素D和海洋omega-3脂肪酸补充剂对心脏健康和癌症预防的影响。我们提出了一项令人兴奋的子研究，在65岁以上的重要参与者中进行认知测试，以评估海洋omega-3脂肪和维生素D是否在维持男性和女性的认知功能方面可能是重要的。

DESCRIPTION (provided by applicant): The VITAL (VITamin D and OmegA-3 TriaL) study was recently funded (recruitment starts January 2010) to investigate the effects of vitamin D and marine omega-3 fatty acid supplements on the primary prevention of cardiovascular disease and cancer. We propose to initiate a substudy of cognitive decline (VITAL-Cog) among 3000 participants aged 65+years, including 1000 African-Americans. This is an exciting opportunity to conduct a large and highly cost-effective randomized double-blind placebo-controlled 2x2 factorial trial of vitamin D (vitamin D3 [cholecalciferol], 2000 IU/day) and marine omega-3 fatty acid (docosahexaenoic acid + eicosapentaenoic acid, 1000 mg/day) supplements for slowing cognitive decline. Data from laboratory studies, epidemiologic research, small primary prevention trials, and/or large secondary prevention trials suggest that these nutritional agents may reduce cognitive decline, but large trials among a generally healthy aging population are lacking. Growing public enthusiasm for supplemental vitamin D as well as fish oil underscores the urgent need for a timely initiation of such a trial, before their use becomes sufficiently prevalent (through supplements and food fortification). VITAL participants will be recruited from the general population by mail among health and other professionals, members of AARP, subscribers to Essence magazine, and others; African-Americans will be oversampled, as they have a higher prevalence of vitamin D deficiency. Respondents will be enrolled in a 3-month placebo run-in phase to test participation. We propose to administer baseline telephone cognitive testing during the run-in period, permitting a pre-randomization assessment. The telephone cognitive battery will include 7 tests of general cognition, verbal memory, and executive function (we have extensive experience with telephone cognitive testing, and the battery will be validated in 300 VITAL-Cog participants with in-person cognitive tests). 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 4.5 years. Blood samples will be collected to allow assessment of effect modification by baseline 25-hydroxyvitamin D, omega-3 fatty acid levels, as well as by apolipoprotein E4 status. At 1-year intervals, participants will receive a new supply of pills and a follow-up questionnaire on compliance, possible side effects and medical history. At 1.5 to 2-year intervals, VITAL-cog participants will receive follow-up cognitive function assessments, for a total of 3 assessments over the 4.5 years; participants in the 10th percentile of worst decline will also receive telephone informant interviews using the Dementia Questionnaire. Given our success with prior telephone based cognitive function assessments in multiple trial settings, we believe VITAL-cog will be able to provide definitive results regarding the study hypotheses. To complete pre-randomization assessment of cognitive function, it is critical that VITAL-Cog be undertaken in parallel to the placebo run-in period for the parent trial (1 U01 CA138962), which is scheduled to begin in April 2010. PUBLIC HEALTH RELEVANCE: Given the projected aging of the population, maintaining cognitive function into older ages is of major public health importance, and early interventions may be most effective. The VITAL (VITamin D and OmegA-3 TriaL) study was recently funded and will begin recruitment in January 2010 to investigate the effects of vitamin D and marine omega-3 fatty acid supplements on heart health and cancer prevention. We propose an exciting substudy, incorporating cognitive testing among VITAL participants aged 65+ years to evaluate whether marine omega-3 fatty and vitamin D may be important in the maintenance of cognitive function in men and women.