Arthritis and Traditional Chinese Medicine

描述（由申请方提供）：相关性：骨关节炎（OA）是关节炎最常见的形式，是发病、活动受限和医疗保健利用的主要原因，尤其是在老年人中。疼痛和功能受限是OA的主要临床表现。膝关节OA是关节炎患者中最常见的关节疾病之一。由于目前没有治愈性治疗膝关节骨性关节炎，管理包括控制疼痛和减少功能限制。然而，一些最常见的治疗方法，如非甾体抗炎药，与严重的副作用，包括胃肠道紊乱和心血管风险。阿片类药物可用于治疗慢性疼痛，但其使用也受到不良反应和成瘾风险的限制。据报道，约50%的持续性疼痛患者缺乏有效的疼痛控制。传统中医（TCM）在亚洲社会广泛用于治疗膝关节骨性关节炎，在美国也被许多人使用。然而，其使用的科学依据相对较少。最近的数据表明，炎症在OA的病理生理学中起着重要作用，涉及疼痛和僵硬的产生以及结构进展。中医传统上采用混合草药的复合配方来治疗各种疾病。活络消苓丹是我国治疗关节炎已有400多年历史的古方。我们已经发现，传统的中国全草药治疗活络消灵（HLXL）丹的11个草药配方在动物模型中具有显着的抗炎作用。它的11种草药中有10种被证明具有抗炎特性，9种具有镇痛特性。 项目概要：我们建议进行一项随机、安慰剂对照、双盲、II期剂量递增临床试验，以找到HLXL提取物作为180例40岁及以上诊断为膝关节OA患者的连续治疗的最佳有效、安全和耐受剂量。每个剂量水平的60例受试者将以2：1的分配比例随机分配至HLXL或安慰剂组。他们将接受6周治疗，并在基线、2、4和6周时使用有效、可靠和反应性指标-西安大略麦克马斯特（WOMAC）骨关节炎指数、患者总体评估（PGA）和医学结局研究简表36（MOS SF-36）等评估疼痛和功能受限的临床重要结局。我们将记录不良事件和症状，并进行血液和尿液分析，ECG和体格检查。我们将通过药丸计数和日记评估治疗方案的依从性，并跟踪伴随药物和治疗的使用。我们将检测C反应蛋白，并将测量环氧化酶（考克斯）1和2活性作为炎症和疾病的生物标志物。

DESCRIPTION (provided by applicant): Relevance: Osteoarthritis (OA) is the most common form of arthritis and is a major cause of morbidity, limitation of activity and health care utilization, especially in the elderly. Pain and functional limitation are the primary clinical manifestations of OA. Knee OA is one of the most common joint disorders among patients with arthritis. As there are presently no curative therapies for OA of the knee, management consists of control of pain and reduction in functional limitation. However, some of the most common therapeutic approaches such as non-steroidal anti-inflammatory drugs are associated with severe side effects including gastrointestinal disturbances and cardiovascular risks. Opioids can be used to manage chronic pain, but their use is also limited by adverse effects and the risk of addiction. It has been reported that about 50% of persistent pain sufferers lack effective pain control. Traditional Chinese Medicine (TCM) is widely used to treat OA of the knee in Asian societies and is used by many in the United States. The scientific basis for its use however, is relatively sparse. Recent data suggest that inflammation plays an important role in the pathophysiology of OA with respect to both the production of pain and stiffness, and structural progression. Chinese medicine has traditionally employed mixtures of herbs in composite formulas for the treatment of various ailments. Huo-Luo-Xiao-Ling (HLXL) Dan is an ancient polyprescription that has been used for more than 400 years in the treatment of arthritis in China. We have found that an 11 herb formulation of the traditional Chinese whole herbal remedy Huo-Luo-Xiao-Ling (HLXL) Dan has significant anti-inflammatory effects in animal models. Ten of its eleven herbs are documented to have anti-inflammatory properties, and nine to have analgesic properties. Project summary: We propose to conduct a randomized, placebo-controlled, double-blind, phase II dose escalation clinical trial to find an optimally efficacious, safe, and tolerable dosage of HLXL extract as adjunctive treatment in 180 patients, aged 40 and over, diagnosed with OA of the knee. Sixty participants at each dosage level will be randomized to HLXL or placebo in a 2:1 allocation ratio. They will be treated for 6 weeks and assessed at baseline, 2, 4, and 6 weeks for the clinically important outcomes of pain and functional limitation using valid, reliable and responsive measures - the Western Ontario McMaster (WOMAC) Osteoarthritis Index, the Patient Global Assessment (PGA), and the Medical Outcomes Study Short Form 36 (MOS SF-36), among others. We will record adverse events and symptoms and conduct blood and urine analyses, ECGs, and physical examinations. We will assess adherence with the treatment regimen via pill counts and diary, and track concomitant drug and treatment use. We will assay C reactive protein and will measure cyclo-oxygenase (COX) 1 and 2 activity as biological markers of inflammation and disease.