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。疼痛和功能受限是骨性关节炎的主要临床表现。膝骨性关节炎是关节炎患者中最常见的关节疾病之一。由于目前尚无根治方法治疗膝骨性关节炎，治疗方法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，如非类固醇抗炎药，与严重的副作用有关，包括胃肠道紊乱和心血管风险。阿片类药物可用于控制慢性疼痛，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。中医药在亚洲社会被广泛用于治疗膝骨性关节炎，在美国也有许多人使用。然而，使用它的科学基础相对较少。最近的数据表明，炎症在骨性关节炎的病理生理学中扮演着重要的角色，包括疼痛和僵硬的产生，以及结构的进展。传统上，中医在治疗各种疾病的复方中使用草药的混合物。活络消灵丹是中国治疗关节炎的一种古老的方剂，已有400多年的历史。我们发现中药活络消灵丹(HLXL)的11种中药配方在动物模型上具有显著的抗炎作用。它的11种草药中有10种被证明具有抗炎特性，9种具有止痛特性。 项目摘要：我们建议进行一项随机、安慰剂对照、双盲、II期剂量递增的临床试验，以寻找HLXL提取物作为辅助治疗的最佳有效、安全和可耐受的剂量，用于180名年龄在40岁及以上的膝骨性关节炎患者。每个剂量水平的60名参与者将按2：1的分配比例随机服用HLXL或安慰剂。他们将接受为期6周的治疗，并在基线、2周、4周和6周使用有效、可靠和灵敏的测量方法--西部安大略省麦克马斯特(WOMAC)骨关节炎指数、患者总体评估(PGA)和医疗结果研究简表36(MOS SF-36)等-评估疼痛和功能受限的临床重要结果。我们将记录不良事件和症状，并进行血和尿分析、心电图和体检。我们将通过药片计数和日记来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，并将检测环氧合酶(COX)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.