Project 1 - Dose Escalation Study of Chinese Herbs in Osteoathritis of the Knee

相关：骨关节炎(OA)是最常见的关节炎形式，也是发病率的主要原因， 限制活动和保健利用，特别是在老年人。疼痛和功能受限是 骨性关节炎的主要临床表现。膝骨性关节炎是患者中最常见的关节疾病之一。 患有关节炎。由于目前尚无根治膝骨性关节炎的疗法，管理包括 控制疼痛，减少功能限制。然而，一些最常见的治疗方法 非类固醇抗炎药等方法与严重的副作用有关，包括 胃肠紊乱和心血管风险。阿片类药物可以用来治疗慢性疼痛，但 它们的使用也受到不良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。中医药被广泛应用于 在亚洲社会治疗膝骨性关节炎，在美国被许多人使用。智能交通系统的科学基础 然而，使用相对稀少。最近的数据表明，炎症在高血压中起着重要作用。 就疼痛和僵硬的产生以及结构进展而言，骨性关节炎的病理生理学。 中医传统上在复方中使用草药混合物来治疗 各种疾病。活络消灵丹是一种古老的方剂，已被广泛使用 400多年来在中国治疗关节炎。我们发现一种11草药配方的 传统中药活络消灵丹(S^JD^F)具有显著的抗衰老作用。 动物模型中的炎症效应。据记载，它的11种草药中有10种具有抗炎作用 其中9种具有止痛作用。 项目摘要：我们建议进行一项随机、安慰剂对照、双盲、II期剂量试验。 升级临床试验，寻找HLXL提取物AS的最佳有效、安全和可耐受的剂量 180例40岁及以上膝关节骨关节炎患者的辅助治疗。60名与会者参加了 每个剂量水平将按2：1的分配比例随机分配给HLXL或安慰剂。他们将接受6年的治疗 在基线、2周、4周和6周评估疼痛和疼痛的临床重要结局 使用有效、可靠和响应措施的功能限制--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 缩写表格36(MOS SF-36)等。我们将记录不良事件和症状并进行 血液和尿液分析，心电图和体检。我们将评估治疗的依从性 通过药片计数和日记进行养生，并跟踪伴随药物和治疗的使用。我们将化验C反应 蛋白，并将测定环氧合酶(COX)1和2的活性作为炎症和 疾病。

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 (S^Jd^F]-) 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.