Curcuma longa L. in Rheumatoid Arthritis (CLaRA): Clinical Planning Study

描述(由申请人提供)：NCCAM已将治疗肌肉骨骼疼痛的各种剂型的姜黄素/姜黄素确定为优先研究领域，包括生物利用度和药代动力学参数的比较，目的是确定合适的患者群体，优化干预措施，并为更大规模的临床试验确定适当的结果指标。利用类风湿性关节炎(RA)的实验模型，本提案的PI先前在NCCAM/ods资助的研究中对姜黄素/姜黄素在RA中的抗炎作用进行了详细分析，这是一种特别具有炎症和关节破坏性的关节炎形式，研究了疗效、生物活性部分和作用机制。我们现在建议在此基础上，将我们的发现转化为临床领域的初步研究，评估姜黄素/姜黄素治疗RA的可行性和耐受性，包括初步评估剂量、姜黄素类化合物和潜在生物活性代谢物的生物利用度，以及对已知的抗炎活性RA生物标志物的影响大小的估计。建议进行一项双臂双盲试点研究，评估具有增强生物利用度的商业可得姜黄素制剂的两种剂量。项目第一年将是一个管理期，专门用于获得IND和IRB的批准，以及所有与议定书相关的文件的定稿。项目第2-3年将专门用于临床试验本身，将检验对甲氨蝶呤反应不充分的活动性疾病的生物幼稚RA患者给予姜黄素的可行性和耐受性，包括药代动力学研究和对已知炎症生物标志物的影响大小的估计。这项临床规划研究的最终目标是获得数据，以指导一项大型临床试验(姜黄素治疗类风湿性关节炎[Clara])的设计，评估姜黄素在治疗慢性炎症性肌肉骨骼疾病--类风湿性关节炎--关节疼痛和炎症中的抗炎效果。

DESCRIPTION (provided by applicant): NCCAM has identified as a high priority research area the evaluation of various formulations of turmeric/curcumin for the treatment of musculoskeletal pain, including comparisons of bioavailability and pharmacokinetic parameters, with the goal of identifying an appropriate patient population, optimizing the intervention, and identifying appropriate outcome measures for a larger clinical trial. Using an experimental model of rheumatoid arthritis (RA), the PI of this current proposal has previously performed a detailed analysis of the anti-inflammatory effects of turmeric/curcumin in RA, a particularly inflammatory and joint destructive form of arthritis, in NCCAM/ODS-funded studies examining efficacy, bioactive moieties and mechanism of action. We now propose to build upon this knowledge base, translating our findings into the clinical arena in a preliminary study assessing the feasibility and tolerability of turmeric/curcumin use in RA, including an initial assessment of doses, bioavailability of curcuminoids and potentially bioactive metabolites, and estimates of effect size on known RA biomarkers of anti-inflammatory activity. A two-arm doubled blinded pilot study assessing two doses of a commercially available curcuminoid formulation with enhanced bioavailability is proposed. Project year 1 will be an administrative period devoted to obtaining IND and IRB approval, as well a finalization of all protocol related documents. Project Years 2-3 will be devoted to the clinical trial itself, which will examine the feasibility and tolerability of administering curcuminoids to biologic naive RA patients with active disease who have inadequately responded to methotrexate, including pharmacokinetic studies and estimates of effect size on known inflammatory biomarkers. The ultimate goal of this clinical planning study is to obtain data to guide the design of a large clinical trial (Curcuma longa L. in Rheumatoid Arthritis [CLaRA]) assessing the anti-arthritic effects of curcuminoids in the treatment of joint pain and inflammation in a chronic inflammatory musculoskeletal disorder, rheumatoid arthritis.