Lung VITamin D and OmegA-3 TriaL (Lung VITAL)

肺维生素 D 和 OmegA-3 试用版（肺 VITAL）

基本信息

批准号：
8286081
负责人：
DIANE R GOLD
金额：
$ 75.65万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-01 至 2014-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8286081
关键词：
Absenteeism at work Acute Lung Injury Adult Age American Ancillary Study Arachidonic Acids Asthma Blood Breathing Cardiovascular Diseases Cause of Death Cholecalciferol Chronic Obstructive Airway Disease Clinical Trials Collagen Comorbidity Consumption Controlled Clinical Trials Data Deep Vein Thrombosis Diagnosis Dietary intake Digestion Disease Disease Outcome Disease Progression Docosahexaenoic Acids Dose Double-Blind Method Eicosanoids Eicosapentaenoic Acid Enrollment Epidemiologic Studies Epithelial Cells Equilibrium Evaluation Exposure to Fatty Acids Fibroblasts Fish Oils Fishes Forced expiratory volume function Genetic Polymorphism Gram-Negative Bacteria Health Heart failure Hormones Immune Incidence Infection Infectious Lung Disorder Inflammation Inflammatory Response Ingestion Inhibition of Matrix Metalloproteinases Pathway Intake Intervention Lipoxygenase Lung Lung diseases Malignant Neoplasms Marines Modality Morbidity - disease rate Mus Muscle Weakness Nutrient Observational Study Obstruction Obstructive Lung Diseases Omega-3 Fatty Acids Organism Paper Parents Participant Pathway interactions Peptides Phagocytes Pharmaceutical Preparations Placebo Control Placebos Pneumonia Positioning Attribute Prevalence Primary Cancer Prevention Production Public Health Pulmonary Function Test/Forced Expiratory Volume 1 Race Randomized Randomized Clinical Trials Randomized Controlled Trials Research Personnel Respiratory Tract Infections Respiratory physiology Risk Role Safety Schedule Serum Skin Pigmentation Source Steroids Sun Exposure Sunlight Supplementation Symptoms Testing Therapeutic Effect Time United States Viral Vitamin D Vitamin D Deficiency Vitamin D3 Receptor Wheezing Woman Work Wound Healing aged airway obstruction airway remodeling antimicrobial antimicrobial peptide cost effective design disability extracellular fungus high risk improved killings lipid mediator men mortality nutrition osteoporosis with pathological fracture public health relevance pulmonary function pulmonary function decline respiratory smoking cessation

项目摘要

DESCRIPTION (provided by investigator): COPD and pneumonia are among the leading causes of morbidity and mortality in adults 60 years and older, and pneumonia rates are higher for those with COPD. Asthma often coexists with COPD in adults and worsens COPD progression. The current modalities for treatment of COPD are limited, and prevalence of vitamin D deficiency is high. COPD lung disease (COPD, asthma, airflow obstruction), and most COPD additional co-morbidities responsible for COPD progression (e.g., respiratory infections/pneumonia, muscle weakness, cardiac failure) may benefit from vitamin D supplementation therapy but this requires rigorous testing. Marine omega-3 fatty acids work through different pathways from vitamin D to modulate inflammation. We have carefully evaluated the dose of each of these supplements to achieve the best balance of efficacy and safety. Observational studies and clinical trials suggest that fish consumption and EPA or DHA may protect against COPD, asthma or pneumonia, but data are not consistent. Thus there is a compelling rationale for a clinical trial to evaluate the potential benefits or risks of vitamin D and marine omega-3 fatty acid supplementation on COPD and asthma exacerbations, airflow obstruction and decline of lung function, and risk of pneumonia. We propose to take advantage of a large-scale randomized clinical trial-the VITamin D and OmegA-3 TriaL (VITAL), whose endpoints are primary prevention of cancer and cardiovascular diseases-to conduct the first major evaluation of the role of vitamin D and long-chain marine omega-3 polyunsaturated fatty acid (eicosapentaenoic acid [EPA] plus docosahexaenoic acid [DHA]) supplementation on obstructive and infectious respiratory disease outcomes. VITAL is a cost-effective, randomized, double-blind, placebo- controlled clinical trial among 20,000 men and women without cancer or CVD at baseline, who are selected on age only (men aged e60 and women aged e65), with an oversampling of blacks. In a 2x2 factorial design, participants will be randomized to moderate-to-high dose vitamin D3 (cholecalciferol; 1600 IU [40 5g]/d) and fish oil (EPA [500 mg/d] + DHA [500 mg/d]) supplements (or placebos) independently. We hypothesize that Vitamin D3 and marine omega-3 fatty acid (EPA+DHA) supplementation will result in reduction of COPD and asthma exacerbations; in reduction in decline of lung function; in improvement of airway obstruction and asthma control; and in reduction of pneumonia in adults. To test our Lung VITAL hypotheses it is essential to complete pre-randomization assessment of baseline respiratory symptom status, COPD and asthma exacerbations in the past year; asthma control and use of controller and rescue medication; pulmonary function; and baseline vitamin D and fatty acid levels. Thus it is critically important that this ancillary study be undertaken in parallel to the enrollment period for the parent VITAL trial (Appendix B), which is scheduled to begin in January 2010. PUBLIC HEALTH RELEVANCE: Chronic obstructive lung disease (COPD) and pneumonia are leading causes of death in United States and world-wide. COPD, which is also a significant source of disability, is increasing in prevalence. Approximately 14 million adults have asthma, which leads to approximately 12 million missed work days per year in the United States. In adults, COPD and asthma often coexist. If vitamin D or marine omega-3 fatty acid supplementation reduce COPD and asthma exacerbations, reduce decline of lung function, improve asthma control and/or reduce pneumonia risk, this would be of great benefit to public health.

描述（由研究者提供）：慢性阻塞性肺病和肺炎是 60 岁及以上成年人发病和死亡的主要原因，慢性阻塞性肺病患者的肺炎发生率更高。成年人中哮喘常常与慢性阻塞性肺病并存，并加剧慢性阻塞性肺病的进展。目前治疗慢性阻塞性肺病的方法有限，而且维生素 D 缺乏症的患病率很高。 COPD 肺部疾病（COPD、哮喘、气流阻塞）以及大多数 COPD 导致 COPD 进展的其他合并症（例如呼吸道感染/肺炎、肌肉无力、心力衰竭）可能受益于维生素 D 补充剂治疗，但这需要严格的测试。海洋 omega-3 脂肪酸通过与维生素 D 不同的途径发挥作用，调节炎症。我们仔细评估了每种补充剂的剂量，以实现功效和安全性的最佳平衡。观察性研究和临床试验表明，食用鱼类和 EPA 或 DHA 可以预防慢性阻塞性肺病、哮喘或肺炎，但数据并不一致。因此，进行临床试验来评估补充维生素 D 和海洋 omega-3 脂肪酸对慢性阻塞性肺病和哮喘恶化、气流阻塞和肺功能下降以及肺炎风险的潜在益处或风险是有令人信服的理由的。我们建议利用一项大规模随机临床试验——维生素 D 和 OmegA-3 TriaL (VITAL)，其终点是癌症和心血管疾病的一级预防——对维生素 D 和 OmegA-3 的作用进行首次重大评估。长链海洋 omega-3 多不饱和脂肪酸（二十碳五烯酸 [EPA] 加二十二碳六烯酸 [DHA]）补充剂对阻塞性和传染性呼吸道疾病的影响。 VITAL 是一项经济高效、随机、双盲、安慰剂对照的临床试验，受试者为 20,000 名基线时没有癌症或 CVD 的男性和女性，仅根据年龄（男性年龄为 60 岁，女性年龄为 65 岁）进行选择，过采样为黑人。在 2x2 因子设计中，参与者将被随机分配至中高剂量维生素 D3（胆钙化醇；1600 IU [40 5g]/天）和鱼油（EPA [500 毫克/天] + DHA [500 毫克/天]））独立补充（或安慰剂）。我们假设补充维生素 D3 和海洋 omega-3 脂肪酸 (EPA+DHA) 将减少慢性阻塞性肺病和哮喘发作；减少肺功能下降；改善气道阻塞和哮喘控制；并减少成人肺炎的发生。为了检验我们的 Lung VITAL 假设，有必要完成去年基线呼吸道症状状态、COPD 和哮喘恶化的随机化前评估；哮喘控制以及控制器和救援药物的使用；肺功能；以及基线维生素 D 和脂肪酸水平。因此，至关重要的是，这项辅助研究必须与计划于 2010 年 1 月开始的母体 VITAL 试验（附录 B）的入组期同时进行。公共卫生相关性：慢性阻塞性肺病 (COPD) 和肺炎是美国和世界范围内的主要原因。慢性阻塞性肺病也是残疾的一个重要原因，其患病率正在增加。在美国，大约有 1400 万成年人患有哮喘，这导致每年大约有 1200 万个工作日缺勤。在成人中，慢性阻塞性肺病和哮喘常常同时存在。如果补充维生素D或海洋omega-3脂肪酸能够减少慢性阻塞性肺病和哮喘发作、减少肺功能下降、改善哮喘控制和/或降低肺炎风险，这将对公众健康大有裨益。