Preventing Incident Knee Osteoarthritis: The Osteoarthritis Prevention Study (TOPS)

预防膝骨关节炎：骨关节炎预防研究 (TOPS)

• 批准号: 9978413
• 负责人: Stephen P Messier
• 金额: $ 25.44万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9978413
• 关键词: Adherence; Adult; Analgesics; Attenuated; Blinded; Body Weight; Body Weight decreased; Boston; Cartilage; Clinic; Clinical; Clinical Trials; Clinical Trials Design; Communication; Consent; Data; Degenerative polyarthritis; Diagnostic radiologic examination; Diet; Disease; Elderly; Exercise; Female; Future; Gadolinium; Gait; Goals; Grant; Health; Hormones; Hospitals; Image; Inflammation; Inflammatory; Institutional Review Boards; Intervention; Knee; Knee Osteoarthritis; Knee joint; Magnetic Resonance Imaging; Manuals; Mechanics; Medial; Medical; Methods; Modeling; Monitor; North Carolina; Obesity; Outcome; Pain; Participant; Prevention; Preventive measure; Procedures; Proteoglycan; Protocols documentation; Quality Control; Randomized Clinical Trials; Reaction Time; Reading; Research; Research Ethics Committees; Research Personnel; Risk; Safety; Self Efficacy; Series; Sex Differences; Site; Statistical Data Interpretation; Surveys; Symptoms; System; Technology; Testing; Thick; TimeLine; Training; Universities; Update; Visit; Weight; Woman; adult obesity; articular cartilage; base; clinical research site; cost effectiveness; cytokine; data collection methodology; data management; diet and exercise; disability; disorder prevention; forest; high risk; improved; inclusion criteria; intervention effect; joint inflammation; joint loading; medical schools; meetings; multi-site trial; prevent; recruit; sex; symposium; therapy design; time use; trial design; willingness

Abstract Osteoarthritis (OA) is the leading cause of disability among older adults; in the absence of a cure, the need for primary preventive measures is essential. The objective of this R34 is to plan an assessor- blinded, 48-month, multi-center, randomized clinical trial designed to (a) establish intensive diet and exercise as an efficacious intervention for preventing incident symptomatic, radiographic knee OA; and (b) determine the cost-effectiveness of this non-pharmacologic intervention in preventing incident symptomatic, radiographic knee OA in high risk adult females. A substantial body of observational data suggests that interventions designed to attenuate joint loading and inflammation by exercise and weight loss show promise in preventing the onset of knee OA. Greater weight loss is associated with better cartilage health in the medial tibial compartment, including improvements in the quality (increased proteoglycan content) and quantity (attenuated cartilage thickness loss) of medial articular cartilage. Data also indicate that losing as little as 5 kg or 5% of baseline weight may result in as much as a 3-fold reduction in the risk of incident radiographic knee OA in obese women. Our approach of long-term intensive weight loss and exercise as a non- pharmacologic treatment for obese adults with knee OA recently tested in the IDEA trial elicited significant reductions in knee joint loads and pro-inflammatory cytokines, and improvements in self- efficacy. Taken together, these studies provide the clinical and mechanistic underpinning for our premise that dietary weight loss of ≥10% of body weight combined with exercise will improve long-term clinical outcomes (pain and function) and prevent incident knee OA relative to control by reducing joint loads, lowering inflammation, and improving self-efficacy for weight loss in at-risk females. The FDA recognizes OA as a serious disease with an unmet medical need. The importance of OA disease prevention is evident because we presently have no effective disease-modifying interventions, there are substantial safety concerns associated with many pain medications, and there is no cure. This planning grant will provide support to conduct a model recruitment to test feasibility, establish a central IRB, refine the study protocol and retention and adherence plans, finalize a statistical analysis plan, and complete the manual of operating procedures. We will also establish and test a centralized reading protocol for all radiographs, develop training manuals for interventionists, and a detailed project timeline for the future clinical trial.

抽象的 骨关节炎（OA）是老年人残疾的主要原因。在没有治疗的情况下 对主要预防测量的需求至关重要。 R34的目的是计划评估师 盲人，48个月，多中心，随机临床试验，旨在（a）建立密集饮食和 锻炼作为预防发生症状的有效干预措施，放射线照相膝关节；和 （b）确定这种非药物干预在预防事件中的成本效益 高风险成年女性的有症状，射线照相膝关节OA。 大量观察数据表明，旨在减轻关节负荷的干预措施 运动和减肥通过炎症表明有望防止膝盖OA发作。 更大的体重减轻与媒体胫骨隔间中的软骨健康有关，包括 改善质量（增加蛋白聚糖含量）和数量（软骨减弱 厚度损失）介质关节软骨的损失。数据还表明，损失至5公斤或5％ 基线重量可能导致出现射线照相膝关节的风险降低3倍 在肥胖的妇女中。我们的长期体重减轻和运动的方法 最近在IDEA试验中测试的肥胖成年人的药理学治疗 膝关节负荷和促炎细胞因子的显着减少，自我的改善 综上所述，这些研究为我们提供了临床和机械基础 前提，饮食体重减轻≥10％的体重与运动相结合将改善长期 临床结果（疼痛和功能），并通过减少关节来防止发生的膝关节OA与对照 载荷，降低炎症以及提高高危女性体重减轻的自我效能感。 FDA认为OA是一种严重的疾病，具有未满足的医疗需求。 OA的重要性 疾病预防是证据，因为我们目前没有有效的疾病改良干预措施， 与许多止痛药有关，存在实质性的安全问题，并且无法治愈。这 计划赠款将提供支持以进行模型招聘以测试可行性，建立中央 IRB，完善研究方案，保留和依从计划，最终确定统计分析计划，以及 完成操作程序的手册。我们还将建立和测试集中阅读 所有X光片的协议，为干预主义者开发培训手册以及详细的项目时间表 对于将来的临床试验。