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

描述(由申请人提供)：我们建议在一项由美国国立卫生研究院资助的大规模随机试验、维生素D和omega-3试验(VITAL，1 U01 CA 138962)的背景下，评估维生素D3(1600IU/天)和omega-3脂肪酸(二十碳五烯酸+二十二碳六烯酸[DHA]，1g/天)对晚年抑郁和抑郁症状的影响。VITAL是一项2x2因素随机对照试验，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中对心血管疾病和癌症的一级预防效果。我们将解决两个主要目标。首先，我们将测试补充维生素D或omega-3是否可以降低试验中所有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科就诊、诊断和药物治疗的额外数据来确定。其次，我们将测试维生素D或omega-3补充剂在5年的研究期间反复测量的持续情绪得分中，哪一个产生更好的结果。此外，我们将解决三个次要目标。首先，在一项针对1000名高风险参与者的子研究中，我们将测试这些药物是否有效地降低了抑郁的风险，并随着时间的推移降低了抑郁评分。高危参与者被定义为具有老年抑郁症已知风险因素(选择性预防)或亚综合征抑郁症状(指示预防)的人。这项子研究的参与者将在美国四个临床和转化科学中心(CTSC)(波士顿、芝加哥、旧金山和休斯顿)招募，并将在基线和两年的随访中接受精神病学访谈(访问将与季节相匹配，以避免对维生素D的季节性偏见)。其次，我们将讨论非洲裔美国人是否改变了补充维生素D对抑郁症风险和整个重要队列中情绪评分的影响(非洲裔美国人受维生素D缺乏的影响不成比例)。第三，在嵌套式病例对照设计中，我们将评估基线血浆维生素D和omega-3脂肪酸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。我们还将能够探索这些制剂的相加和/或协同效应，以及年龄、性别、基线营养水平、基线医学合并症、纬度和体力活动对效果的影响。总之，这项建议提出了一种高效和创新的战略，以同时评估维生素D和omega-3脂肪酸补充剂在普遍、选择性和有针对性地预防老年抑郁症方面的有效性，并提供可能影响这一益处的相关生理参数的特征。我们要求资金用于抑郁症病例确定、精神病学评估和嵌套病例对照样本中随机前血液维生素D和脂肪酸水平的分析。为了检验我们的假设并完成随机化前的精神病学评估，这项辅助研究与定于2010年开始的父母重要试验的登记阶段同时进行，这是至关重要的，也是具有时间敏感性的。 与公共健康相关：生物学和观察性证据支持维生素D和海洋omega-3脂肪酸对精神健康的潜在益处。然而，目前尚不清楚使用这些补充剂是否可以预防老年抑郁症的发生，或者是否可以显著减少老年抑郁症状。这项拟议的研究是在对60岁及以上的美国成年人进行的一项大型临床试验中进行的，研究结果将澄清补充维生素D和/或omega-3脂肪酸是否可以降低老年抑郁症和抑郁症状的风险，并将提供重要的数据，这些数据将适用于公共卫生和抑郁症的一级和二级预防临床指南。

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.