Phased Exploratory Clinical Studies of Harpagophytum procumbens’ Impact upon the Biological Signature of Inflammatory Osteoarthritis

Harpagophytum procumbens 对炎症性骨关节炎生物学特征的影响的分阶段探索性临床研究

• 批准号: 9095048
• 负责人: William Robert Folk
• 金额: $ 19.12万
• 依托单位: UNIVERSITY OF MISSOURI KANSAS CITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9095048
• 关键词: Address; Adverse effects; American; Animal Model; Area; Arthritis; Biological; Biological Availability; Biological Markers; Botanicals; C-reactive protein; Chronic low back pain; Claw; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Data; Degenerative polyarthritis; Dinoprostone; Dose; Drug Kinetics; Effectiveness; Emotional; Ensure; Enteral; Enteric-Coated Tablets; European; Formulation; Future; Goals; Headache; Health; Health Expenditures; Human; Incidence; Individual; Inflammatory; Inflammatory Arthritis; Integrative Medicine; Interleukin-6; Joints; Knee Osteoarthritis; Legal patent; Leukotrienes; Lipoxygenase; Low Back Pain; Manuals; Measures; Medical; Methodology; Monitor; Musculoskeletal; Musculoskeletal Pain; Natural Products; Neuralgia; Outcome; Outcome Measure; Pain; Pain management; Participant; Patients; Pharmaceutical Preparations; Phase; Prevalence; Procedures; Protocols documentation; Randomized; Rattus; Recruitment Activity; Research; Research Infrastructure; Research Priority; Resistance; Rheumatism; Safety; Sample Size; Series; Serum; Site; Societies; Source; Southern Africa; Staging; Symptoms; Synovial Fluid; System; TNF gene; Thromboxane B2; TimeLine; Toxicology; Uncaria procumbens; United Kingdom; United States; United States National Institutes of Health; Urine; aqueous; arthritic pain; base; burden of illness; chronic pain; clinical efficacy; clinical research site; cost; cytokine; effective therapy; efficacy trial; harpagoside; in vivo; loss of function; meetings; operation; patient population; population based; prospective

 DESCRIPTION (provided by applicant): Musculoskeletal conditions represent a major source of pain, loss of function, and health care expenditure that costs Americans many billions, yearly. People with conditions causing chronic pain turn to integrative health practices to supplement other conventional medical treatment, or when their pain is resistant to or in an effort to avoid side effects of medications. However, scientific evidence of safety, efficacy and mechanisms of such practices are limited. European clinical research has provided evidence for safety and efficacy of the botanical Harpagophytum procumbens (H. procumbens or Devil's Claw) for many patients suffering from arthritis and chronic low back pain. The variability in the natural products, however, and lack of a well-defined biological signature necessitate additional exploratory studies with well-characterized products, so that subsequent clinical studies of appropriate methodological rigor can be conducted. The proposed project will use a well characterized product to assess a biological signature for a hypothesized mechanism of action. The R21 phase of the proposed project will address the following objectives: (1) further define the bioavailability and short term pharmacokinetics of the principal secondary metabolites of a well-characterized aqueous-ethanolic extract of H. procumbens in non-enteric and enteric formulations; (2) define the biological signature and hypothetical mechanism of action of the H. procumbens extract in patients with early stage inflammatory knee osteoarthritis over four week dosing; and, (3) develop protocol, data and safety monitoring plan and manual of operations/procedures and obtain all necessary regulatory approvals for the R33 phase. Following successful completion of the R21 phase, the following objectives will be addressed during the R33 phase: (1) confirm and extend assessment of the impact of the H. procumbens extract upon the biological signature of the above referenced systemic inflammatory biomarkers and biomarkers in synovial fluid of patients consuming either of two doses over twelve weeks; and, (2) evaluate the relationship between changes in systemic and local joint biomarker levels and clinical outcomes (pain, stiffness, functional difficulty). Completion of this study will ensure that future clinical trials can be conducted with the methodological rigor and outcome measures needed to appropriately evaluate the effectiveness of H. procumbens products.

 描述（由申请人提供）：肌肉骨骼疾病是疼痛，功能丧失和医疗保健支出的主要来源，每年花费美国人数十亿美元。患有引起慢性疼痛的疾病的人转向综合健康实践，以补充其他常规药物治疗，或者当他们的疼痛抵抗或努力避免药物的副作用时。然而，关于这种做法的安全性、有效性和机制的科学证据有限。欧洲的临床研究已经为植物性的平卧哈帕格植物的安全性和有效性提供了证据。对于许多患有关节炎和慢性腰痛的患者来说，然而，天然产物的变异性和缺乏明确的生物学特征需要对具有良好特征的产品进行额外的探索性研究，以便可以进行适当方法学严谨性的后续临床研究。拟议的项目将使用一种充分表征的产品来评估一种假设的作用机制的生物特征。该项目的R21阶段将实现以下目标：（1）进一步确定已充分表征的水乙醇提取物的主要次级代谢产物的生物利用度和短期药代动力学。非肠溶和肠溶制剂中的平卧层;（2）定义H.在早期炎性膝骨关节炎的患者中进行为期四周的平卧草提取物给药;以及（3）制定方案、数据和安全性监测计划以及操作/程序手册，并获得R33阶段的所有必要的监管批准。在成功完成R21阶段之后，将在R33阶段处理以下目标：（1）确认和扩大对H.根据以上提及的全身性炎症生物标志物和在十二周内消耗两个剂量中的任一个的患者的滑液中的生物标志物的生物特征，评估平卧草提取物;和（2）评估全身和局部关节生物标志物水平的变化与临床结果（疼痛、僵硬、功能困难）之间的关系。本研究的完成将确保未来的临床试验能够以适当评估H.的产品。