VITAL-DEP: Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL

描述（由申请人提供）：我们建议在nih资助的大规模随机试验中评估维生素D3 （1600 IU/天）和omega-3脂肪酸（二十碳五烯酸[EPA] +二十二碳六烯酸[DHA]， 1g/天）补充剂对晚年抑郁和抑郁症状风险的影响，维生素D和omega-3试验（VITAL, 1 U01 CA 138962）。VITAL是一项2x2因子随机对照试验，旨在评估维生素D3和海洋omega-3脂肪酸补充剂在2万名美国老年男性和女性心血管疾病和癌症一级预防中的功效。我们将解决两个主要目标。首先，我们将测试维生素D或omega-3补充剂是否能降低所有试验参与者的抑郁症发病率和复发率。抑郁症病例将通过问卷调查和来自医疗保险和医疗补助服务中心数据库的精神病学访问、诊断和药物的额外数据来确定。其次，在5年的研究期间，我们将测试维生素D或omega-3补充剂是否能在重复测量中产生更好的持续情绪得分。此外，我们将讨论三个次要目标。首先，在一项包含1000名高风险参与者的亚研究中，我们将测试这些药物在降低抑郁风险和降低抑郁评分方面是否有效，高风险参与者被定义为具有已知的晚年抑郁风险因素（选择性预防）或具有亚综合征抑郁症状（指示性预防）的人。本亚研究的参与者将在美国的四个临床和转化科学中心（CTSC）站点（波士顿、芝加哥、旧金山和休斯顿）招募，并将在基线和2年随访时接受精神病学访谈（访问将根据季节进行匹配，以避免维生素D的季节性偏差）。其次，我们将探讨在整个VITAL队列中，非裔美国人种族是否会改变维生素D补充对抑郁风险和情绪评分的影响（非裔美国人受维生素D不足的影响不成比例）。第三，在巢式病例对照设计中，我们将评估维生素D和omega-3脂肪酸的基线血浆水平是否与抑郁症风险相关，以及它们是否会改变治疗效果。我们还将能够探索药物的加性和/或协同效应，以及年龄、性别、基线营养水平、基线医疗合并症、纬度和身体活动对效果的影响。总之，本研究提出了一种高效和创新的策略，可以同时评估维生素D和omega-3脂肪酸补充剂在普遍、选择性和指示性预防老年抑郁症方面的功效，并提供可能影响这种益处的相关生理参数的表征。我们请求资金用于抑郁症病例的确定、精神病学评估以及在巢式病例对照样本中进行随机化前血液中维生素D和脂肪酸水平的分析。为了检验我们的假设并完成预随机化的精神病学评估，这项辅助研究必须与预定于2010年开始的母体VITAL试验的入组期同时进行，这一点至关重要，而且时间敏感。

DESCRIPTION (provided by applicant): We propose to evaluate the effects of vitamin D3 (1600 IU/day) and omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA], 1g/day) supplements on risk of late-life depression and depressive symptoms in the setting of an NIH-funded large-scale randomized trial, the VITamin D and OmegA-3 TriaL (VITAL, 1 U01 CA 138962). VITAL is a 2x2 factorial RCT designed to evaluate the efficacy of vitamin D3 and marine omega-3 fatty acid supplements in the primary prevention of cardiovascular disease and cancer among 20,000 older U.S. men and women. We will address two primary aims. First, we will test whether vitamin D or omega-3 supplementation reduces incident and recurrent depression rates among all participants in the trial. Cases of depression will be identified using questionnaires and additional data on psychiatric visits, diagnoses, and medications from the Centers for Medicare and Medicaid Services database. Second, we will test whether vitamin D or omega-3 supplementation yields better continuous mood scores on repeated measures over the 5-year study period. In addition, we will address three secondary aims. First, in a substudy of 1,000 high-risk participants, defined as persons with known risk factors for late-life depression (selective prevention) or with subsyndromal depressive symptoms (indicated prevention), we will test whether the agents are effective at reducing risk of depression and at yielding lower depression scores over time. Participants in this substudy will be recruited at four Clinical and Translational Science Center (CTSC) sites across the U.S. (Boston, Chicago, San Francisco, and Houston), and will undergo a psychiatric interview at baseline and at 2 years of follow-up (visits will be matched for season, to avoid seasonal bias for vitamin D). Second, we will address whether African-American race modifies effects of vitamin D supplementation on depression risk and on mood scores in the entire VITAL cohort (African-Americans are disproportionately affected by vitamin D insufficiency). Third, in a nested case-control design, we will assess whether baseline plasma levels of vitamin D and omega-3 fatty acids are related to depression risk, and whether they modify treatment effects. We will also be able to explore additive and/or synergistic effects of the agents, as well as effect modification by age, gender, baseline nutrient levels, baseline medical comorbidity, latitude, and physical activity. In summary, this proposal presents a highly efficient and innovative strategy to evaluate simultaneously the efficacy of vitamin D and omega-3 fatty acid supplementation for universal, selective and indicated prevention of late-life depression, as well as to provide characterization of relevant physiologic parameters that may influence this benefit. We request funds for depression case ascertainment, psychiatric assessments, and assays of pre-randomization blood levels of vitamin D and fatty acids in a nested case-control sample. In order to test our hypotheses and to complete pre- randomization psychiatric assessments, it is critically important and time-sensitive that this ancillary study be undertaken in parallel to the enrollment period for the parent VITAL trial, which is scheduled to begin in 2010. PUBLIC HEALTH RELEVANCE: Biologic and observational evidence supports potential mental health benefits of both vitamin D and marine omega-3 fatty acids. However, it remains unclear whether the use of these supplements can prevent onset of late-life depression or can significantly reduce depressive symptoms in late-life. Findings from this proposed study, conducted within a large clinical trial among U.S. adults aged 60 years and above, will clarify whether vitamin D and/or omega-3 fatty acid supplementation reduces risk of late-life depression and depressive symptoms, and will provide important data that will be applicable to public health and clinical guidelines for both primary and secondary prevention of depression.