Treatment of Rheumatoid Arthritis-Marine/Botanical Oils

类风湿关节炎的治疗-海洋/植物油

• 批准号: 6905539
• 负责人: ROBERT B ZURIER
• 金额: $ 74.73万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6905539
• 关键词: T lymphocyte; alternative medicine; arachidonate; arthritis therapy; clinical research; clinical trial phase III; diet therapy; dietary supplements; gene expression; human subject; human therapy evaluation; inflammation; marine animal oil; nutrition related tag; omega 3 fatty acid; patient oriented research; plant extracts; radiography; rheumatoid arthritis; tumor necrosis factor alpha

DESCRIPTION (provided by applicant): The object of this proposal is to determine whether treatment of rheumatoid arthritis (RA) with a combination of fish oil and borage seed oil is superior to treatment with either oil alone. Fish oil is rich in the antiinflammatory n3 unsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and borage oil contains gammalinolenic acid (GLA), an n6 unsaturated fatty acid with antiinflammatory and immunomodulatory properties. Administration of borage oil and of fish oil both suppress the clinical manifestations of RA. Animal studies indicate that the mechanisms whereby fish oil suppresses inflammation are both similar to and different from the means by which GLA reduces inflammation and that the combination treatment is more effective than each treatment alone. This proposal is for a multi-center, two-year, phase 3, double-masked, placebo-controlled trial of 375 patients, which includes 4 treatment groups: 1) corn oil as a polyunsaturated fatty acid control; 2) fish oil; 3) borage oil; 4) fish oil plus borage oil. Radiographic analysis (Sharp Scores) of hands and feet will be done at baseline, 12, and 24 months. Biochemical and molecular mechanisms whereby the fatty acid treatments influence activation of monocytes (cytokine and oxygen radical generation), and T lymphocytes (proliferation, cytokine production, Th1/Th2 skewing, signaling events) will be investigated. Results of the cell activation (ex vivo) studies will be correlated with clinical outcomes. Results of these studies should raise awareness of the usefulness of naturally occurring oils in inflammatory diseases, lead to more rational use of fatty acids in treatment of inflammatory arthritis, and provide a greater understanding of the mechanisms of action of antiinflammatory fatty acids.

描述（由申请人提供）：本提案的目的是确定用鱼油和琉璃苣籽油的组合治疗类风湿性关节炎（RA）是否上级单独使用任一种油的治疗。 鱼油富含n3不饱和脂肪酸二十碳五烯酸（EPA）和二十二碳六烯酸（DHA），琉璃苣油含有γ-亚麻酸（GLA），这是一种具有抗氧化和免疫调节特性的n6不饱和脂肪酸。 琉璃苣油和鱼油的管理都抑制类风湿关节炎的临床表现。 动物研究表明，鱼油抑制炎症的机制与GLA减少炎症的机制既相似又不同，联合治疗比单独治疗更有效。 该提案是针对375例患者的多中心、两年、III期、双盲、安慰剂对照试验，其中包括4个治疗组：1）玉米油作为多不饱和脂肪酸对照; 2）鱼油; 3）琉璃苣油; 4）鱼油加琉璃苣油。 将在基线、12个月和24个月时进行手部和足部的放射学分析（Sharp评分）。 将研究脂肪酸处理影响单核细胞（细胞因子和氧自由基产生）和T淋巴细胞（增殖、细胞因子产生、Th 1/Th 2偏斜、信号传导事件）活化的生化和分子机制。细胞活化（离体）研究的结果将与临床结局相关。 这些研究的结果应该提高人们对天然油在炎症性疾病中的有用性的认识，导致更合理地使用脂肪酸治疗炎症性关节炎，并提供对脂肪酸作用机制的更好理解。