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

描述（由申请人提供）：NCCAM已确定为一个高度优先的研究领域，评价姜黄/姜黄素的各种制剂用于治疗肌肉骨骼疼痛，包括生物利用度和药代动力学参数的比较，目的是确定适当的患者人群，优化干预措施，并确定适当的结果措施，用于更大的临床试验。使用类风湿性关节炎（RA）的实验模型，本提案的PI先前已在NCCAM/ODS资助的研究中详细分析了姜黄/姜黄素在RA（一种特别具有炎症和关节破坏性的关节炎形式）中的抗炎作用，检查了疗效、生物活性部分和作用机制。我们现在建议建立在这一知识基础上，将我们的发现转化为临床竞技场，在初步研究中评估姜黄/姜黄素用于RA的可行性和耐受性，包括剂量的初步评估，姜黄素和潜在生物活性代谢物的生物利用度，以及对已知RA抗炎活性生物标志物的效应大小的估计。提出了一项评估两种剂量的具有增强的生物利用度的市售姜黄素制剂的双臂双盲初步研究。项目第1年将是一个管理期，用于获得IND和IRB批准，以及所有方案相关文件的定稿。项目第2-3年将致力于临床试验本身，该试验将研究对甲氨蝶呤反应不充分的活动性疾病的生物初治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效应大小估计。本临床计划研究的最终目的是获得数据以指导大型临床试验的设计（姜黄L。in Rheumatoid Arthritis [CLaRA]）评价类姜黄素在治疗慢性炎性肌肉骨骼疾病类风湿性关节炎中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.