Multisite RCT Investigating the Efficacy of Massage in Osteoarthritis

描述（由申请人提供）：骨关节炎（OA）是关节炎的最常见形式，是一种缓慢进行的关节软骨退行性疾病，折磨着4000万美国人。现有的药物疗法（对乙酰氨基酚、非甾体抗炎药（NSAID）和COX-II抑制剂）可以帮助控制疼痛，但它们的使用通常受到毒性的限制，并且它们通常不能完全缓解症状。按摩疗法和其他补充和替代药物（CAM）干预措施正在被OA患者使用，并代表有吸引力的，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，具有高安全性，低不良事件的轮廓时，由训练有素的按摩治疗师管理。 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OA按摩疗法的试点试验。该研究于2006年发表在《内科学文献》上，将68名受试者随机分为按摩干预组或等待对照组，并证明了瑞典按摩疗法在治疗膝关节OA方面的疗效，治疗后持续8周。本申请旨在进行一项随访、对照试验，以最终确定该治疗的疗效。拟定的是一项多中心随机化等待列表对照试验（n=170），通过初始剂量探索阶段确定按摩对膝关节OA的效用。 主要目的是确定和评估一个合适的按摩剂量的治疗效果作为治疗膝关节骨性关节炎。该假设是，根据西安大略和麦克马斯特大学骨关节炎指数（WOMAC）（一种经验证的自我管理工具，用于评估疼痛、僵硬和功能）的评估，在8周时间内，标准剂量的瑞典按摩疗法将导致干预组与对照组膝关节骨关节炎受试者相比临床显著改善。 次要目标包括：1）4种不同方案的剂量探索阶段（共80例）对OA患者进行8周瑞典式按摩，以确定最合适的剂量进行全面评估; 2）确定8周按摩治疗的安全性; 3）确定瑞典式按摩导致的其他替代结局的临床显著改善; 4）评估按摩治疗效果的持续时间; 5）通过量化炎性细胞因子、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）来研究按摩对膝关节OA的作用机制;以及6）测量与OA管理和按摩干预相关的资源利用和直接医疗、直接非医疗和生产力成本。拟议中的试验将确立按摩疗法在OA患者治疗选择中的适当位置。 公共卫生相关性：骨关节炎（OA）是关节炎的最常见形式，是一种缓慢进行的，使人衰弱的关节软骨退行性疾病，困扰着3000万美国人。OA的常规治疗通常不能完全消除症状，并且具有潜在的毒性，这使得需要探索其他治疗方法。这项研究的目的是确定按摩疗法作为治疗膝关节骨性关节炎继发性疼痛和残疾患者的效用，因此可能会减轻全球数百万人的痛苦。

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.