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

描述（由申请人提供）：NCCAM已经确定了姜黄/姜黄素治疗肌肉骨骼疼痛的各种配方的评估作为一个高度优先的研究领域，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，并为更大的临床试验确定适当的结果措施。使用类风湿关节炎（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/姜黄素在RA（一种特别炎症和关节破坏形式的关节炎）中的抗炎作用进行了详细分析，研究了其疗效、生物活性部分和作用机制。我们现在建议在这个知识库的基础上，将我们的发现转化为临床领域的初步研究，评估姜黄/姜黄素在RA中使用的可行性和耐受性，包括对剂量的初步评估，姜黄素和潜在的生物活性代谢物的生物利用度，以及对已知RA生物标志物抗炎活性的效应大小的估计。提出了一项两臂双盲试点研究，评估两种剂量的市售姜黄素制剂与增强的生物利用度。项目第一年将是一个行政期间，致力于获得IND和IRB的批准，以及所有协议相关文件的最后确定。项目第2-3年将致力于临床试验本身，该试验将检验姜黄素治疗对甲氨蝶呤反应不足的活动性生物初发类风湿性关节炎患者的可行性和耐受性，包括药代动力学研究和对已知炎症生物标志物的效应大小估计。本临床计划研究的最终目的是获取数据，以指导大型临床试验（Curcuma longa L. in Rheumatoid Arthritis [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的关节疼痛和炎症中的抗关节炎作用。

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.