Vitamin D and Fish Oil for Autoimmune Disease, Inflammation and Joint Pain

维生素 D 和鱼油治疗自身免疫性疾病、炎症和关节疼痛

• 批准号: 7861111
• 负责人: Karen H Costenbader
• 金额: $ 55.73万
• 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: 2010-05-07 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7861111
• 关键词: Adult; Adverse effects; Age; Aging; American; Ancillary Study; Anti-Inflammatory Agents; Anti-inflammatory; Arthralgia; Arthritis; Attention; Autoantibodies; Autoimmune Diseases; Biological Markers; Blood specimen; Body mass index; C-reactive protein; Calcium; Cardiovascular Diseases; Cells; Cholecalciferol; Chronic; Cohort Studies; Consent Forms; Controlled Clinical Trials; Data; Degenerative polyarthritis; Development; Diabetes Mellitus; Diet; Disease; Disease susceptibility; Docosahexaenoic Acids; Dose; Double-Blind Method; Economic Burden; Eicosapentaenoic Acid; Elderly; Enrollment; Epidemiologic Studies; Expenditure; Fish Oils; Funding; General Population; Generations; Health Benefit; Homeostasis; Immune; Immune system; Incidence; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Bowel Diseases; Interleukin-6; Laboratory Study; Letters; Leukotrienes; Literature; Mails; Marines; Medical; Medical History; Medical Records; Morbidity - disease rate; Muscle; Nutritional; Observational Study; Omega-3 Fatty Acids; Outcome; Pain; Parents; Participant; Pathway interactions; Persons; Pharmaceutical Preparations; Physicians; Placebo Control; Placebos; Polymyalgia Rheumatica; Population; Prevention; Preventive; Primary Cancer Prevention; Primary Prevention; Production; Prostaglandins; Psoriasis; Questionnaires; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Recruitment Activity; Reducing Agents; Reporting; Research Infrastructure; Rheumatoid Arthritis; Risk; Role; Running; Screening procedure; Supplementation; Testing; Therapeutic; Time; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; Validation; Vitamin D; Woman; aged; autoimmune thyroid disease; base; bone turnover; cigarette smoking; cytokine; design; dietary supplements; disability; disorder risk; follow-up; immune activation; knee pain; member; men; older men; pill; prevent; protective effect; public health relevance; randomized trial; retiree; success; systemic autoimmune disease

DESCRIPTION (provided by applicant): - We propose to leverage a newly NIH-funded large, randomized, double-blind, placebo-controlled, 2x2 factorial trial of vitamin D (in the form of vitamin D3 [cholecalciferol]) and marine omega-3 fatty acid (eicosapentaenoic acid [EPA] + docosahexaenoic acid [DHA]) supplements to study effects upon autoimmune disease incidence, biomarkers of systemic inflammation, and chronic knee pain. Data from laboratory studies, epidemiologic research, and small prevention trials strongly suggest that these nutritional agents reduce the risk of autoimmune diseases, reduce levels of circulating pro-inflammatory cytokines, and decrease chronic joint pain. However, large primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) have never been conducted. The growing enthusiasm for supplemental vitamin D and fish oils underscores the urgent need for their timely testing, before their use becomes so prevalent as to render participant recruitment and hypothesis testing impossible. The NIH-funded VITAL randomized controlled trial about to begin will involve 20,000 men aged e60 and women aged e65 recruited from a mailing to 1.2 million persons, including members of AARP (formerly known as the American Association of Retired Persons), and others. The mailing will contain a letter describing the trial, an informed consent form, and a questionnaire about past medical history, including autoimmune diseases and a screening assessment of chronic knee pain, as well as diet, medication and nutritional supplement use. At the end of a 3 month placebo 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 5 years: vitamin D3 (1600 IU/d) and fish oil (EPA+DHA, 1 g/d); vitamin D3 and fish oil placebo; placebo vitamin D3 and fish oil; and placebo vitamin D3 and placebo fish oil. At yearly intervals, participants will receive a new supply of pills, and assessments of incident autoimmune diseases, knee pain, compliance and potential side effects. A physician endpoints committee will confirm all autoimmune disease endpoints by medical record review. We anticipate validation of 600 incident cases of autoimmune disease, giving us sufficient statistical power to assess supplement effects on disease incidence. Blood samples at baseline and in follow-up will be collected in a random subcohort of 2000 individuals and analyzed for changes in biomarkers of systemic inflammation: C-reactive protein, interleukin-6, and tumor necrosis factor-a. Approximately 2000 individuals with chronic, frequent knee pain will be followed with annual questionnaires, providing ample statistical power to evaluate the supplement effects upon chronic knee pain. To complete the pre-randomization assessment of knee pain, it is critically important that this ancillary study be undertaken in parallel to enrollment for the parent VITAL trial, beginning January 2010. Given the NIH-funded VITAL trial and our success with prior large mail-based trials and cohort studies, the proposed trial will furnish either definitive positive or informative null results regarding the central study hypotheses. PUBLIC HEALTH RELEVANCE: The purported health benefits of vitamin D and marine omega-3 fatty acids for preventing autoimmune diseases, decreasing inflammation and relieving joint pain are receiving increasing attention in the medical literature and the popular press. However, definitive data supporting these health benefits of these two readily available over-the-counter agents are lacking. Findings from this large randomized clinical trial will clarify the roles of vitamin D and marine omega-3 fatty acid supplements for the prevention of autoimmune diseases, effects on levels of biomarkers of systemic inflammation, and treatment for chronic knee pain in older men and women.

描述（由申请人提供）： - 我们提议利用新的NIH资助的大型，随机，双盲，安慰剂对照，2x2维生素D（以维生素D3的形式）（胆钙化脂蛋白）的形式（以维生素D3的形式）自身免疫性疾病发病率，全身炎症的生物标志物和慢性膝盖疼痛。实验室研究，流行病学研究和小型预防试验的数据强烈表明，这些营养剂降低了自身免疫性疾病的风险，降低循环促炎性细胞因子的水平并减轻慢性关节疼痛。但是，从未进行过大型的初级预防试验，并从未进行过适当的剂量（即未选择疾病风险）。对补充维生素D和鱼油的越来越多的热情强调了对及时测试的迫切需求，在使用之前，它们的使用变得如此普遍，以使参与者的招募和假设测试不可能。 NIH资助的生命随机对照试验即将开始，将涉及20,000名E60年龄的男性和从邮件中招募到120万人的E65妇女，包括AARP（以前称为美国退休人员协会）等人。邮寄将包含一封描述试验的信，知情同意书以及有关过去病史的问卷，包括自身免疫性疾病以及对慢性膝盖疼痛的筛查评估以及饮食，药物和营养补充剂的使用。在安慰剂的3个月结束时，那些愿意和符合条件的人，报告至少三分之二的药丸的人将被随机分配给四个治疗组之一：维生素D3（1600 IU/d）和鱼油（EPA+DHA，1 g/d）；维生素D3和鱼油安慰剂；安慰剂维生素D3和鱼油；和安慰剂维生素D3和安慰剂鱼油。每年的时间间隔，参与者将获得新的药丸供应，并评估事件自身免疫性疾病，膝盖疼痛，依从性和潜在的副作用。医师端点委员会将通过病历审查确认所有自身免疫性疾病终点。我们预计会验证600例自身免疫性疾病事件，从而为我们提供足够的统计能力来评估补充对疾病发病率的影响。基线和随访时的血液样本将在2000个个体的随机亚细胞中收集，并分析了系统性炎症的生物标志物的变化：C反应蛋白，白介素6和肿瘤坏死因子A。大约有2000名患有慢性，频繁膝盖疼痛的人会随着年度问卷调查，提供足够的统计能力来评估对慢性膝盖疼痛的补充作用。为了完成对膝关节疼痛的随机化评估，至关重要的是，这项辅助研究是从2010年1月开始的。鉴于NIH资助的重要试验，并通过先前的基于邮寄的大型试验和同类研究的成功进行，这项拟议的试验将提供确定性的积极或信息性的NULL研究结果。 公共卫生相关性：维生素D和海洋omega-3脂肪酸所谓的健康益处，可防止自身免疫性疾病，减少炎症和缓解关节疼痛在医学文献和大众媒体上引起了人们的关注。但是，缺乏支持这两个容易获得的非处方药的确定性数据。这项大型随机临床试验的发现将阐明维生素D和海洋omega-3脂肪酸补充剂在预防自身免疫性疾病方面的作用，对全身炎症的生物标志物的影响以及老年男性和女性的慢性膝盖疼痛治疗的影响。