ANTIBIOTIC THERAPY FOR RHEUMATOID ARTHRITIS (ATRA TRIAL)

类风湿性关节炎的抗生素治疗（ATRA 试验）

• 批准号: 6273983
• 负责人: Eugene William St. Clair
• 金额: $ 2.88万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6273983
• 关键词: antirheumatic agents; azithromycin; clinical research; collagenase; connective tissue disorder chemotherapy; drug screening /evaluation; enzyme activity; human subject; human therapy evaluation; rheumatoid arthritis; tetracyclines

Previous randomized, controlled clinical trials suggest that oral tetracyclines may reduce the symptoms of joint inflammation in rheumatoid arthritis (RA). This class of antibiotics has well-described antimicrobial effects as well as anti-collagenase activity. Collagenase is an enzyme that degrades cartilage and bone and is believed to be important in the pathogenesis of RA. This study evaluates the safety and potential clinical efficacy of I.V. doxycycline therapy in 60 patients with RA and will explore whether any improvements in arthritis from the doxycycline are due to its antibacterial actions or ability to reduce the activity of collagenase. The three objectives of this study are: 1) To determine the feasibility, safety, and potential clinical efficacy of I.V. doxycycline therapy in RA and explore whether this agent ameliorates clinical manifestations of this disease by suppressing bacterial infection or matrix metalloproteinases (MMP) activity; 2) To determine whether daily and weekly treatment with I.V. doxycycline can reduce urinary excretion of collagen crosslinks in patients with RA and potentially retard joint damage; and 3) To explore the potential effects of daily and weekly I.V. doxcycline therapy on biochemical markers of cartilage proteoglycan degradation; and 4) to determine whether IV doxycycline can reduce expression of nitric oxide synthase type 2 expressed by circulatory monocytes.

之前的随机对照临床试验表明，口服 四环素类药物可减轻类风湿关节炎的症状 关节炎(RA)。这类抗生素已经被很好地描述 抑菌效果以及抗胶原酶活性。胶原酶 是一种降解软骨和骨骼的酶，据信 在类风湿关节炎的发病机制中起重要作用。本研究对其安全性和安全性进行了评价 静脉注射多西环素治疗60例潜在临床疗效 并将探索是否有任何改善关节炎的 多西环素是由于它的抗菌作用或减少 胶原酶活性。 这项研究的三个目标是：1)确定可行性， 多西环素静脉注射治疗类风湿关节炎的安全性和潜在临床疗效 并探讨该制剂是否能改善本病的临床表现。 通过抑制细菌感染或基质金属蛋白酶而引发的疾病 (2)确定每日和每周的治疗是否与 静脉注射多西环素可减少大鼠尿胶原交联物的排泄 RA患者和可能延缓关节损害的患者；以及3)探索 每日和每周静脉注射多西环素的潜在疗效 软骨蛋白多糖降解的生化标志物；4) 确定静脉注射多西环素是否能减少一氧化氮的表达 由循环单核细胞表达的合成酶2型。