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: 6243962
• 负责人: Eugene William St. Clair
• 金额: $ 3.24万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1975
• 资助国家: 美国
• 起止时间: 1975-10-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6243962
• 关键词: antirheumatic agents; azithromycin; clinical research; clinical trial phase I; 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. Patients will be randomized into 3 groups: Group I receives I.V. doxycycline and oral placebo, Group II will receives I.V. placebo and oral azithromycin, and Group III receives I.V. and oral placebo. The I.V. therapy will be delivered through a peripheral long-line catheter. The initial treatment phase consists of daily infusions and oral therapy for 21 days. The second treatment phase consists of weekly infusions administered from week 4 through 11.

先前的随机对照临床试验表明，口服 四环素类药物可以减轻关节炎的症状， 类风湿性关节炎（RA）。这类抗生素已经被很好地描述 抗微生物作用以及抗胶原酶活性。 胶原酶 是一种降解软骨和骨骼的酶， 在RA的发病机制中起重要作用。 这项研究评估了 和潜在的临床疗效静脉注射强力霉素治疗60 并将探讨是否有任何改善关节炎 是由于它的抗菌作用或能力， 降低胶原酶活性。 本研究的三个目标是：1）确定可行性， 安全性和潜在的临床疗效，静脉注射多西环素治疗 RA，并探讨这种药物是否改善临床表现 通过抑制细菌感染或基质 金属蛋白酶（MMP）活性; 2）以确定是否每天和 每周一次静脉注射多西环素治疗可减少尿中 RA患者的胶原交联和潜在的关节延迟 3）探讨每日和每周一次静脉注射的潜在影响。 强力霉素治疗对软骨蛋白多糖生化指标的影响 降解 将患者随机分为3组：第I组接受静脉注射。 II组接受静脉注射安慰剂， 口服阿奇霉素，组III接受静脉注射和口服安慰剂。 的 静脉注射治疗将通过外周长线导管进行。 初始治疗阶段包括每日输液和口服治疗 21天。 第二个治疗阶段包括每周输注 从第4周到第11周。