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

项目1 - 中药治疗膝骨关节炎的剂量递增研究

• 批准号: 7549313
• 负责人: BRIAN M BERMAN
• 金额: $ 11.58万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7549313
• 关键词: Acetaminophen; Adherence; Adverse effects; Adverse event; Analgesics; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Arthritis; Asians; Biological Assay; Biological Markers; Blood; C-reactive protein; Caring; China; Chinese Herbs; Chinese People; Chinese Traditional Medicine; Clinical; Clinical Trials; Count; Data; Degenerative polyarthritis; Diagnosis; Disease; Dose; Double-Blind Method; Drug Formulations; Elderly; Functional disorder; Herb; Herbal Medicine; Inflammation; International; Knee; Knee Osteoarthritis; Measures; Medical; Medicine; Modality; Morbidity - disease rate; National Center for Complementary and Alternative Medicine; Ontario; Opioid; Outcome; Outcome Study; Pain; Pain management; Participant; Patients; Persistent pain; Persons; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Physical Examination; Placebo Control; Placebos; Play; Policies; Production; Property; Randomized; Reporting; Research; Risk; Role; SF-36; Safety; Societies; Standards of Weights and Measures; Symptoms; Therapeutic; Treatment Protocols; United States; United States Food and Drug Administration; Urine; Week; addiction; aged; arthropathies; base; cardiovascular risk factor; chronic pain; cyclooxygenase 1; design; diaries; dosage; functional improvement; gastrointestinal; health care service utilization; improved; indexing; pill; response

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.

相关性：骨关节炎（OA）是关节炎最常见的形式，是发病的主要原因， 活动和医疗保健利用受限，尤其是老年人。疼痛和功能限制是 OA的主要临床表现。膝关节OA是患者中最常见的关节疾病之一 关节炎由于目前尚无膝关节OA的治愈性疗法，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 诸如非甾体抗炎药的方法与严重的副作用相关， 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 它们的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。传统中医（TCM）被广泛用于 在亚洲社会治疗膝关节骨性关节炎，在美国被许多人使用。其科学依据 然而，使用相对较少。最近的数据表明，炎症在炎症中起着重要作用。 关于疼痛和僵硬的产生以及结构进展的OA的病理生理学。 中医传统上采用复合配方中的草药混合物来治疗 各种疾病。活络消苓丹是一种古老的复方制剂， 在中国治疗关节炎已有400多年的历史。我们已经发现，11种草药的配方， 传统中药活络消灵丹具有明显的抗肿瘤作用， 在动物模型中的炎症作用。它的11种草药中有10种被证明具有抗炎作用 属性，和九个具有镇痛特性。 项目概述：我们拟开展一项随机、安慰剂对照、双盲、II期剂量- 逐步扩大的临床试验，以找到HLXL提取物的最佳有效、安全和耐受剂量， 180例40岁及以上膝关节OA患者的连续治疗。60名与会者， 每个剂量水平将以2：1的分配比例随机分配至HLXL或安慰剂组。他们将被治疗6 在基线、第2、4和6周时评估临床重要的疼痛结局， 使用有效、可靠和反应性措施的功能限制-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 Short Form 36（MOS SF-36）等。我们将记录不良事件和症状， 血液和尿液分析、ECG和体格检查。我们将评估治疗的依从性 通过药丸计数和日记记录给药方案，并跟踪伴随药物和治疗使用。我们将检测C反应性 蛋白质，并将测量环加氧酶（考克斯）1和2活性作为炎症的生物标志物， 疾病