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: 8654296
• 负责人: Karen H Costenbader
• 金额: $ 50.98万
• 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 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8654296
• 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; Supplementation; Testing; Therapeutic; Time; Tumor Necrosis Factor-alpha; United States National Institutes of Health; 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; older women; pill; prevent; protective effect; public health relevance; randomized trial; retiree; screening; 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.

描述（由申请人提供）： - 我们建议利用 NIH 新资助的大型、随机、双盲、安慰剂对照、2x2 因子试验，研究维生素 D（以维生素 D3 [胆钙化醇] 的形式）和海洋 omega- 3 种脂肪酸（二十碳五烯酸 [EPA] + 二十二碳六烯酸 [DHA]）补充剂，用于研究对自身免疫性疾病发病率、全身炎症生物标志物和慢性膝盖疼痛。来自实验室研究、流行病学研究和小型预防试验的数据强烈表明，这些营养剂可以降低自身免疫性疾病的风险，降低循环促炎细胞因子的水平，并减轻慢性关节疼痛。然而，从未在普通人群中进行过足够剂量的大型初级预防试验（即未针对疾病风险进行选择）。人们对补充维生素 D 和鱼油的热情日益高涨，这凸显了在其使用变得如此普遍以至于无法招募参与者和进行假设检验之前对其进行及时测试的迫切需要。即将开始的由 NIH 资助的 VITAL 随机对照试验将涉及 20,000 名年龄在 60 岁的男性和年龄在 65 岁的女性，这些人是通过邮寄方式招募的 120 万人，其中包括 AARP（以前称为美国退休人员协会）的成员和其他人。邮件将包含一封描述试验的信件、一份知情同意书和一份有关既往病史的调查问卷，包括自身免疫性疾病和慢性膝关节疼痛的筛查评估，以及饮食、药物和营养补充剂的使用。在 3 个月的安慰剂磨合期结束时，那些仍然愿意且符合资格，并且报告已服用至少三分之二药物的患者，将被随机分配到四个治疗组之一，为期 5 年：维生素 D3（ 1600 IU/天）和鱼油（EPA+DHA，1克/天）；维生素 D3 和鱼油安慰剂；安慰剂维生素 D3 和鱼油；安慰剂维生素 D3 和安慰剂鱼油。每隔一年，参与者将收到新的药丸，并对发生的自身免疫性疾病、膝盖疼痛、依从性和潜在副作用进行评估。医生终点委员会将通过病历审查确认所有自身免疫性疾病终点。我们预计将验证 600 例自身免疫性疾病病例，从而为我们提供足够的统计能力来评估补充剂对疾病发生率的影响。基线和随访时的血液样本将在 2000 名个体的随机分组中收集，并分析全身炎症生物标志物的变化：C 反应蛋白、白细胞介素 6 和肿瘤坏死因子 -a。大约 2000 名患有慢性、频繁膝盖疼痛的人将接受年度调查问卷，为评估补充剂对慢性膝盖疼痛的效果提供充足的统计能力。为了完成膝盖疼痛的随机化前评估，至关重要的是，这项辅助研究与 2010 年 1 月开始的 VITAL 试验的入组并行进行。考虑到 NIH 资助的 VITAL 试验以及我们之前大型邮件试验的成功，基于试验和队列研究，拟议的试验将提供有关中心研究假设的明确的阳性结果或信息性无效结果。