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

维生素 D 和 OmegA-3 试验中的 VITAL-DEP 抑郁症终点预防

• 批准号: 8990077
• 负责人: Olivia Ifeoma Okereke
• 金额: $ 85.29万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-29 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8990077
• 关键词: Address; African American; Age; Anxiety; Attention; Bioavailable; Biochemical; Biological; Biological Assay; Biological Markers; Blood specimen; Brain-Derived Neurotrophic Factor; Center for Translational Science Activities; Cholecalciferol; Clinical; Clinical Research; Clinical Sciences; Data; Data Set; Diagnostic; Elderly; Ensure; Fish Oils; Funding; Health; Health Benefit; Incidence; Individual; Interview; Long-Term Effects; Malignant Neoplasms; Marines; Measures; Mediating; Mediator of activation protein; Mental Depression; Mental Health; Minority; Minority Participation; Moods; Neuropsychological Tests; Nutrient; Omega-3 Fatty Acids; Outcome; Parents; Participant; Patient Self-Report; Performance; Personal Satisfaction; Persons; Plasma; Prevention; Public Health; Race; Randomized; Recurrence; Research Infrastructure; Resources; Risk Factors; Sampling; Serum; Social Functioning; Specific qualifier value; Structure; Supplementation; Symptoms; Testing; Time; Variant; Vitamin D; Woman; Work; aged; behavioral health; cohort; daily functioning; data integrity; depression prevention; depressive symptoms; design; ethnic difference; follow-up; geriatric depression; heart disease prevention; high risk; men; novel; novel marker; positive mood; prevent; public health relevance; racial and ethnic; racial difference; racial/ethnic difference; randomized trial; response; social; treatment duration; treatment effect; trial design

 DESCRIPTION (provided by applicant): VITAL-DEP (Depression Endpoint Prevention in the VITamin D and OmegA-3 TriaL) is an ongoing, large- scale, 2x2 factorial randomized trial of vitamin D (vitamin D3 [cholecalciferol] 2000 IU/d) and omega-3 fatty acids (EPA and DHA, in 1:1 ratio, 1000 mg/d) for the prevention of late-life depression and promotion of long- term benefits for mood. In the first funding period (9/29/10-06/30/15), we completed baseline and early follow- up of depression outcomes among nearly 19,000 successfully randomized men and women, aged 50+ years (mean age=65y), who were eligible for incidence or recurrence of late-life depression; nearly 70% of participants have provided pre-randomization blood samples for nutrient biochemical assays. Furthermore, in the Clinical and Translational Science Center (CTSC) component, detailed phenotypic assessments were conducted among a subset of over 1,000 individuals who received in-person structured psychiatric diagnostic interviews, underwent neuropsychological testing, and provided data on dimensional measures of mood, well- being, and social and daily functioning. Finally, another landmark aspect of VITAL-DEP is its substantial racial and ethnic diversity: over 25% of participants are from minority racial and/or ethnic backgrounds, including 19% who are African American. Indeed, our first funding period aims emphasized potential differences in vitamin D response among African Americans, given high risk of low 25(OH)D in this group. However, late- breaking evidence indicates that bioavailable vitamin D is of greatest relevance to race/ethnic differences. In this 5-year renewal proposal, we expand upon what has been achieved in the first period - assembly of a unique trial cohort - and focus on the unprecedented scientific opportunities afforded by this RCT design. Our Primary Aims are: 1) to extend follow-up of mood to examine with high statistical power the long-term (up to 7 years) effects of vitamin D and marine omega-3 fatty acids on depression outcomes among all ~19,000 participants; 2) to examine with high power the impact of biochemical nutrients levels of vitamin D and omega- 3 fatty acids on depression outcomes as well as treatment interaction with baseline biochemical levels. Secondary Aims focus on two critical themes that our particular trial design is uniquely poised to address: 1) racial/ethnic differences in long-term treatment effects; 2) mechanisms, mediators and moderators of mood effects of vitamin D and fish oil in this diverse cohort. Specifically, in a sub-set of 2,000 participants, we will examine relations of bioavailable vitamin D to depression, with attention to race differences in outcomes. Further, among the entire eligible CTSC cohort, we will obtain pre- and post-randomization serum brain- derived neurotrophic factor and targeted plasma metabolite levels to examine biological paths involved in mood responses to vitamin D and fish oil treatment and to test whether biomarker change explains variation in treatment effects. Thus, this proposal not only will ensure comprehensive, definitive testing of the benefits of vitamin D and fish oil for late-life mood but also will inform specific mechanisms involved in a diverse sample.

 描述（由申请人提供）：VITAL-DEP（维生素D和OmegA-3 TriaL中的抑郁终点预防）是一项正在进行的大规模、2x2析因随机试验，研究维生素D（维生素D3 [胆钙化醇] 2000 IU/d）和ω-3脂肪酸（EPA和DHA，比例为1：1，1000 mg/d）用于预防晚年抑郁症和促进对情绪的长期益处。在第一个供资期间（2010年9月29日至2015年6月30日），我们在近19，000名成功随机化的男性和女性中完成了抑郁结局的基线和早期随访，年龄50岁以上（平均年龄= 65岁），这些人有资格发生或复发晚年抑郁症;近70%的参与者提供了随机化前的血液样本用于营养生化测定。此外，在临床和转化科学中心（CTSC）部分，对超过1，000名接受面对面结构化精神病诊断访谈、接受神经心理学测试并提供情绪、幸福感以及社交和日常功能维度测量数据的个体进行了详细的表型评估。最后，VITAL-DEP的另一个标志性方面是其巨大的种族和民族多样性：超过25%的参与者来自少数种族和/或民族背景，包括19%的非裔美国人。事实上，我们的第一个资助期的目标是强调非裔美国人对维生素D反应的潜在差异，因为这一群体中低25（OH）D的风险很高。然而，最新的证据表明，生物可利用的维生素D与种族/民族差异最相关。在这个为期5年的更新提案中，我们扩展了第一阶段所取得的成就-组装了一个独特的试验队列-并专注于这项RCT设计所提供的前所未有的科学机会。我们的主要目标是：1）扩展情绪随访，以高统计功效检查维生素D和海洋omega-3脂肪酸对所有约19，000名参与者中抑郁症结局的长期（长达7年）影响; 2）以高功效检查维生素D和omega- 3脂肪酸的生化营养素水平对抑郁症结局的影响以及与基线生化水平的治疗相互作用。次要目的集中在两个关键主题，我们的特定试验设计是唯一准备解决：1）长期治疗效果的种族/民族差异; 2）维生素D和鱼油在这个多样化队列中的情绪效应的机制，介质和调节剂。具体来说，在2,000名参与者的子集中，我们将研究生物可利用维生素D与抑郁症的关系，并注意结果的种族差异。此外，在整个合格的CTSC队列中，我们将获得随机化前后的血清脑源性神经营养因子和靶向血浆代谢物水平，以检查涉及对维生素D和鱼油治疗的情绪反应的生物学途径，并测试生物标志物变化是否解释了治疗效果的变化。因此，这项提案不仅将确保全面、明确地测试维生素D和鱼油对晚年情绪的益处，而且还将为不同样本中涉及的特定机制提供信息。