DOXYCYCLINE EFFECT ON OSTEOARTHRITIS PROGRESSION

描述(来自应用程序)： 膝关节骨关节炎(OA)是慢性骨性关节炎最常见的原因 在这个国家，残疾人权利受到严重威胁，并产生巨大的社会经济影响。值得注意的是， 目前对骨性关节炎的治疗仅限于对症治疗。非甾体类 抗炎药(NSAIDs)是最受欢迎的治疗药物 但老年妇女的风险最大，其中尤其常见的是老年妇女。 出现非类固醇抗炎药的严重副作用。然而，值得注意的是，有几个 药物已被证明可以预防或减缓软骨损伤的进展。 在0A的动物模型中，目前正在开发药物来抑制 蛋白水解酶诱导的软骨损伤，以期其在骨关节炎中的应用。我们有 结果表明，预防性口服多西环素(Doxy)显著 降低犬骨关节炎模型中软骨损伤的严重程度； 在软骨损伤建立后开始治疗，一种保护性的 效果是明显的。在豚鼠身上也观察到了类似的结果 兔骨性关节炎模型。这种影响与水平的降低有关。 胶原酶和明胶酶在骨性关节炎软骨中的含量。 基于OA动物模型中令人鼓舞的数据，我们建议进行 多西他滨的多中心、双盲、安慰剂对照临床试验 患有骨关节炎的受试者。我们的假设是DOXY会降低 骨性关节炎的严重程度或进展速度。因为一种治疗疾病的药物 因为办公自动化可能更有可能在早期表现出效果 我们的研究表明，疾病的分期比骨性关节炎的病理更晚期 人口将是2名肥胖女性，年龄在45-60岁之间， 有单侧胫股骨性关节炎的X线证据，其中X射线改变 据报道，在2%的时间内，对侧膝关节的发病率接近50% 好几年了。受试者(n=432)将被随机接受Doxy，100 mg，Bid，或 安慰剂服用两年半。不会试图影响非甾体抗炎药和/或 常规过程中规定的止痛治疗或其他措施 临床护理。将采用几种策略来最大限度地提高合规性 研究中的药物和受试者保留情况，包括 一种“心脏模糊”测试，它将在一开始被用来消除 违规者，并使用计算机化的医药帽来提供信息 关于在两次探视之间遵守规定的剂量方案， 允许研究人员努力加强遵从性，以 那些最能从中受益的研究对象。我们的主要成果 变量将是关节间隙缩窄率(JSN，由 数字化膝关节半屈曲X线片的计算机处理系统 使用一种技术显著降低放射解剖学中的可变性 定位)和OA的个体放射学特征的严重性， 例如，在对侧膝关节中的骨赘。因为JSN在中国的比率 对侧膝关节是不确定的，而公布的数据表明在 表现出骨性关节炎的膝关节(例如骨赘)是 足够快的速度，以允许在 在研究期间，示指膝关节的放射学进展也将服务于 作为主要结果变量。此外，我们还将研究 脑功能指数(WOMAC)、全球关节炎活动、总体健康 状态(SF-36)。两次治疗中的卫生服务利用情况 组。这项研究应该回答这样一个问题，即口服治疗是否与 Doxy-一种相对安全、容易获得和廉价的药物 几十年的临床经验积累了-可以修改自然病史 人类的骨性关节炎。

DESCRIPTION (from the application): Osteoarthritis (OA) of the knee is the most common cause of chronic disability in this country and has enormous socio-economic impact. Notably, management of OA today is limited to symptomatic therapy. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most popular agents used to treat OA but elderly women, in whom OA is especially common, are at greatest risk of developing serious side effects from NSAIDs. Notablly, however, several drugs have been shown to prevent, or slow progression of, cartilage damage in animal models of 0A, and drugs are currently being developed to inhibit protease-induced cartilage damage, with a view to their use in OA. We have shown that prophylactic oral administration of doxycycline (doxy) markedly reduces the severity of cartilage damage in a canine model of OA; even when therapy was initiated after cartilage lesions were established, a protective effect was apparent. Similar results have been noted in guinea pig and rabbit models of OA. The effect is associated with reduction in the levels of collagenase and gelatinase in the OA cartilage. Based on the encouraging data in animal models of OA, we propose to conduct a multi-center, double-blind, placebo-controlled clinical trial of doxy in subjects with OA. It is our hypothesis that doxy will decrease the severity, or rate of progression, of OA. Because a disease-modifying drug for OA will, presumably, be more likely to show an effect in the early stages of the disease than when OA pathology is more advanced, our study population will be 2 obese females, 45-60 years old, with x-ray evidence of unilateral tibiofemoral OA in whom x-ray changes have been reported to develop in the contralateral knee in nearly 50% within 2 years. Subjects (n=432) will be randomized to receive doxy, 100 mg bid, or placebo for 2-1/2 years. No attempt will be made to influence NSAID and/or analgesic treatment or other measures prescribed in the course of routine clinical care. Several strategies will be employed to maximize compliance with the study medications and retention of subjects in the study, including a "faintness-of-heart" test, which will be used at the outset to eliminate noncompliers, and use of a computerized medicine cap to provide information concerning compliance with the prescribed dosing regimen between visits, permitting study personnel to aim their efforts to enhance compliance at those subjects who can best benefit from them. Our primary outcome variables will be the rate joint space narrowing (JSN, measured by a computerized system on a digitized AP radiograph of the semi-flexed knee taken with a technique to markedly reduce variability in radioanatomic positioning) and the severity of individual radiographic features of OA, e.g., osteophytes, in the contralateral knee. Because the rate of JSN in the contralateral knee is uncertain, whereas published data indicate that in knees which exhibit bony changes of OA (e.g., osteophytes) it is sufficiently rapid to permit detection of a reasonable drug effect during the study period, radiographic progression in the index knee will also serve as a primary outcome variable. In addition, we will examine changes in an algofunctional index (WOMAC), global arthritis activity, general health status (SF-36). and utilization of health services in the two treatment groups. This study should answer the question whether oral treatment with doxy - a relatively safe, readily available and inexpensive drug with which decades of clinical experience have accrued - can modify the natural history of OA in humans.