Multisite RCT Investigating the Efficacy of Massage in Osteoarthritis

描述(申请人提供)：骨关节炎(OA)是最常见的关节炎形式，是一种缓慢进展的关节软骨退行性疾病，困扰着4000万美国人。现有的药物疗法(醋氨酚、非类固醇抗炎药(NSAIDs)和COX-II抑制剂)可以帮助控制疼痛，但它们的使用往往受到毒性的限制，而且往往无法完全缓解症状。按摩疗法和其他补充和替代药物(CAM)干预措施正被OA患者使用，是有吸引力的、潜在有效的替代方案。瑞典按摩通常用于缓解肌肉骨骼疾病的疼痛，由训练有素的按摩治疗师提供时，安全性高，不良事件发生率低。 2004年，UMDNJ-SHRP和耶鲁-格里芬预防研究中心进行了一项由CDC支持的膝关节骨关节炎推拿疗法试点试验。这项研究发表在2006年的《内科医学档案》上，将68名受试者随机分为按摩干预组或等待名单对照组，并展示了瑞典按摩疗法对膝盖骨关节炎的治疗效果，治疗后8周仍有疗效。这项应用是为了进行一项随访的对照试验，以最终确定这种治疗的疗效。建议进行一项多部位随机等待名单对照试验(n=170)，由初始剂量发现阶段通知，以确定按摩治疗膝骨性关节炎的有效性。 主要目的是确定和评估治疗膝骨性关节炎的治疗效果的合适剂量的按摩。这个假设是，在为期8周的时间里，标准化剂量的瑞典按摩疗法将导致由西安大略省和麦克马斯特大学OA指数(WOMAC)评估的膝骨性关节炎干预对象与对照组相比在临床上有显著改善。WOMAC是一种经过验证的自我给药工具，用于评估疼痛、僵硬和功能。 次要目标包括：1)4种不同方案(共80个)的剂量发现阶段，对OA患者进行8周的瑞典按摩，以确定最合适的剂量进行彻底评估；2)确定8周按摩治疗的安全性；3)确定瑞典按摩在临床上对其他替代结果的显著改善；4)评估按摩的疗效持续时间；5)通过定量测定炎症细胞因子、II型胶原分解和合成生物标志物、高敏C反应蛋白和抗应激和抗炎激素(DHEA-S)来探讨按摩对膝骨性关节炎的作用机制；以及6)测量资源利用率以及与办公自动化管理和按摩干预相关的直接医疗、直接非医疗和生产力成本。拟议的试验将在骨性关节炎患者的治疗选择中确定适当的推拿治疗地点。 与公共卫生相关：骨关节炎(OA)是最常见的关节炎形式，是一种进展缓慢、使人衰弱的关节软骨退行性疾病，困扰着3000万美国人。传统的治疗骨性关节炎的方法往往不能完全消除症状，并有潜在的毒副作用，这就需要探索其他治疗方法。进行这项研究是为了确定按摩疗法作为治疗继发性膝骨性关节炎后疼痛和残疾患者的有效性，因此可能会减轻世界各地数百万人的痛苦。

DESCRIPTION (provided by applicant): Osteoarthritis (OA), the most common form of arthritis, is a slowly progressive degenerative disease of joint cartilage that afflicts 40 million Americans. Existing pharmacologic therapies (acetaminophen, non- steroidal anti-inflammatories (NSAIDs), & COX-II inhibitors) can help to control pain, but their use is often limited by toxicity, and they often fail to fully alleviate symptoms. Massage therapy and other complementary and alternative medication (CAM) interventions, are being utilized by OA sufferers and represent attractive, potentially effective alternatives. Swedish massage, generally used to relieve pain for musculoskeletal conditions, has a high safety, low adverse event profile when administered by trained massage therapists. In 2004, UMDNJ-SHRP & the Yale-Griffin Prevention Research Center conducted a CDC-supported pilot trial of massage therapy for OA of the knee. That study, published in Archives of Internal Medicine in 2006, randomized 68 subjects to massage intervention or wait-listed control and demonstrated efficacy of Swedish massage therapy in the treatment of OA of the knee, with benefits persisting 8 weeks beyond treatment. This application is to conduct a follow-up, controlled trial to determine conclusively the therapeutic efficacy of this treatment. Proposed is a multi-site randomized wait-list controlled trial (n=170), informed by an initial dose- finding phase, to determine the utility of massage for OA of the knee. The main objective is to identify and evaluate a suitable dose of massage for therapeutic efficacy as a treatment for OA of the knee. The hypothesis is that a standardized dose of Swedish massage therapy over an 8-week period will lead to clinically significant improvement in intervention vs control subjects with OA of the knee as assessed by the Western Ontario & McMaster Universities OA Index (WOMAC), a validated self- administered tool to assess pain, stiffness and function. Secondary Aims include: 1) A dose-finding phase of 4 different regimens (n=80 total) of 8 weeks of Swedish massage in OA patients to determine the most suitable dose for thorough evaluation; 2) Determine the safety profile of 8 weeks of massage therapy; 3) Identify clinically significant improvements in other surrogate outcomes as a result of Swedish massage; 4) Assess the duration of therapeutic effects of massage; 5) Investigate the mechanism of action of massage for OA the knee through the quantitation of inflammatory cytokines, type II collagen breakdown & synthesis biomarkers, high sensitivity C-Reactive Protein and an anti-stress & anti-inflammatory hormone (DHEA-S); and 6) Measure resource utilization and direct medical, direct non-medical and productivity costs associated with OA management and the massage intervention. The proposed trial will establish the proper place for massage therapy among treatment options for OA sufferers. PUBLIC HEALTH RELEVANCE: Osteoarthritis (OA), the most common form of arthritis, is a slowly progressive, debilitating degenerative disease of joint cartilage that afflicts 30 million Americans. Conventional therapies for OA often fail to eliminate symptoms fully and have potential toxicities, which has necessitated the need to explore additional treatments. This study is being conducted to ascertain the utility of massage therapy as a treatment for patients afflicted with pain and disability secondary to OA of the knee and therefore may lead to a lessening of suffering for millions of individuals world-wide.