Novel Insights into Osteoarthritis, Pain and Function: MOST4

对骨关节炎、疼痛和功能的新见解：MOST4

• 批准号: 10555681
• 负责人: DAVID Tobin FELSON
• 金额: $ 1151.4万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-02-29
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10555681
• 关键词: Address; Adverse effects; Affect; Bathing; Biological Markers; Biology; Biomechanics; Calcium; Chronic; Clinical; Clinical Data; Clinical Trials; Clinical Trials Data Monitoring Committees; Communities; Complex; Crystal Formation; Data; Data Collection; Degenerative polyarthritis; Deposition; Deterioration; Diagnostic; Disease; Disease Progression; Elderly; Eligibility Determination; Enrollment; Exercise; Fright; Glues; Goals; Grant; Heterogeneity; Image; Impairment; Inflammation; Inflammatory; Investigation; Joints; K-Series Research Career Programs; Knee; Knee Osteoarthritis; Knowledge; Magnetic Resonance Imaging; Minority Groups; Nervous System; Outcome; Output; Pain; Pain Measurement; Pain management; Participant; Pathology; Patient Participation; Patients; Phenotype; Physical activity; Pilot Projects; Prevention; Proteins; Proteomics; Publishing; Recommendation; Replacement Arthroplasty; Research Personnel; Risk; Risk Factors; Sample Size; Signal Transduction; Source; Synovial Fluid; Talents; Underrepresented Minority; Visualization; Work; advanced disease; blood-based biomarker; career; career development; cohort; data management; disability; disabling disease; disorder prevention; effective therapy; experience; falls; functional decline; functional outcomes; individualized prevention; insight; interdisciplinary approach; knee pain; loss of function; mineralization; novel; novel strategies; novel therapeutic intervention; pain sensitivity; personalized approach; personalized medicine; prognostic; radiological imaging; reconstitution; recruit; response; therapeutic target; therapy development; treatment guidelines

OVERALL ABSTRACT The Multicenter Osteoarthritis (MOST) Study has been a major source of new knowledge about the course of OA and factors that affect it, having published over 180 articles ranging from studies of pain and pain sensitization, to investigations of biomechanics, to inquiries into structural joint pathology as visualized by MRI, and to studies of decline in function, buckling and falls, among others. The initial cohort enrolled 3026 participants with or at risk of knee OA; a new cohort consisting of 1525 subjects was recruited at the last cycle (MOST3) who were slightly younger and unlikely to have advanced disease. We will recruit an additional 150 participants from underrepresented minority groups for a total projected sample size of 2293 in this next cycle of MOST (MOST4). In addition to its scientific output, the study has been remarkable in recruiting and encouraging talented young investigators to take on career defining investigations within MOST, having served as the basis for 31 career development awards. Our overall goal is to advance our understanding of OA and its consequences to open doors to new treatment approaches including stratified approaches to treatments. We will use an integrated approach in the next cycle of MOST (MOST4) overseen by an Administrative Core, involving a Clinical Data Collection and Management Core, Analysis Core, and Imaging Core, with guidance from an Observational Safety Monitoring Board and input from a Community Advisory Board, to efficiently address key knowledge gaps through the conduct of three Projects. Our Specific Aims are to: 1. Evaluate impaired exercise-induced hypoalgesia (EIH) in knee OA, evaluate the relation of nervous system alterations to EIH, and determine the impact of EIH on pain, function, physical activity, and fear-avoidance related to exercise (Project 1); 2. Carry out proteomics analysis of synovial fluid to determine networks of proteins associated with generalized vs. localized OA, pain and disease progression (Project 2); 3. Differentiate types of calcium crystals deposited in the joint and, for each of them, understand the clinical and structural consequences of crystal deposition (Project 3); 4. Take advantage of comprehensive longitudinal data already collected in MOST to address a wide range of questions related to OA and its impact on outcomes; 5. Bring a multidisciplinary approach to bear on this complex disease and offer career development opportunities to investigators including pilot project grants in this understudied condition. MOST4 will introduce new approaches to understanding disease and will continue to comprehensively assess pain, structural, and functional outcomes so that the specific effects of the factors proposed in the Projects and other risk factors can be examined. This work will produce new actionable insights regarding pain, structural deterioration and function loss in knee OA.

总体摘要 多中心骨关节炎 (MOST) 研究是有关骨关节炎病程新知识的主要来源 OA 及其影响因素，已发表 180 多篇文章，涉及疼痛研究 敏化、生物力学研究、MRI 可视化结构关节病理学调查， 以及功能衰退、屈曲和跌倒等方面的研究。初始队列招募了 3026 名参与者 患有膝关节骨关节炎或有膝关节骨关节炎风险；在上一个周期（MOST3）招募了一个由 1525 名受试者组成的新队列，他们 年龄稍小，不太可能患有晚期疾病。我们将另外招募 150 名参与者 在 MOST 的下一个周期 (MOST4) 中，少数群体代表性不足，预计样本总数为 2293 个。 除了科学成果外，该研究在招募和鼓励有才华的年轻人方面也取得了显著成果 调查人员将在 MOST 内进行职业定义调查，作为 31 项职业的基础 发展奖。我们的总体目标是增进我们对 OA 及其开放后果的理解 新治疗方法的大门，包括分层治疗方法。我们将使用一个集成的 由行政核心监督的下一个 MOST (MOST4) 周期中的方法，涉及临床数据 收集和管理核心、分析核心和成像核心，并在观测安全的指导下 监督委员会和社区咨询委员会的意见，以有效解决关键知识差距 通过三个项目的实施。我们的具体目标是： 1. 评估运动引起的受损 膝关节 OA 痛觉减退 (EIH)，评估神经系统改变与 EIH 的关系，并确定 EIH 对疼痛、功能、体力活动和与运动相关的恐惧回避的影响（项目 1）； 2. 执行 对滑液进行蛋白质组学分析，以确定与全身性与局部性相关的蛋白质网络 OA、疼痛和疾病进展（项目 2）； 3. 区分沉积在关节中的钙晶体的类型， 对于每个项目，了解晶体沉积的临床和结构后果（项目 3）； 4. 采取 利用 MOST 中已收集的全面纵向数据来解决广泛的问题 与 OA 及其对结果的影响相关； 5. 采用多学科方法来应对这种复杂的疾病 并为研究人员提供职业发展机会，包括在该研究中提供试点项目资助 健康）状况。 MOST4 将引入了解疾病的新方法，并将继续全面 评估疼痛、结构和功能结果，以便项目中提出的因素产生具体影响 和其他风险因素可以进行检查。这项工作将产生关于疼痛、结构性的新的可操作的见解 膝关节 OA 恶化和功能丧失。