Arthritis and Traditional Chinese Medicine

描述（由申请人提供）：相关性：骨关节炎（OA）是最常见的关节炎形式，是发病率，活动限制和医疗保健利用的主要原因，特别是在老年人中。疼痛和功能限制是OA的主要临床表现。膝关节炎是关节炎患者中最常见的关节疾病之一。由于目前没有治愈膝关节炎的治疗方法，治疗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，与严重的副作用有关，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，但其使用也受到不利影响和成瘾风险的限制。据报道，大约50%的持续性疼痛患者缺乏有效的疼痛控制。中医（TCM）在亚洲社会被广泛用于治疗膝关节OA，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，炎症在骨性关节炎的病理生理学中，无论是疼痛和僵硬的产生，还是结构进展，都起着重要的作用。中医传统上使用草药的混合配方来治疗各种疾病。活络消灵丹是一种古老的复方，在中国用于治疗关节炎已有400多年的历史。我们在动物模型中发现中药活络消灵（hhll）丹的11种中药制剂具有显著的抗炎作用。11种草药中有10种具有抗炎特性，9种具有镇痛特性。

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.