Effect of Intra-Articular Steroids on Structural Progression of Knee OA: An RCT

关节内类固醇对膝关节 OA 结构进展的影响：一项随机对照试验

• 批准号: 8298888
• 负责人: Timothy E McAlindon
• 金额: $ 75.82万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-09 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8298888
• 关键词: Adrenal Cortex Hormones; Adverse effects; Affect; Animal Model; Arthritis; Arthroscopy; Bone Density; Bone Marrow; Cartilage; Clinic; Clinical; Clinical Trials; Consensus; Degenerative polyarthritis; Development; Disease; Double-Blind Method; Dual-Energy X-Ray Absorptiometry; Enrollment; Exhibits; Flare; Futility; Goals; Health Care Costs; High Prevalence; Image; Individual; Inflammation; Inflammatory; Injection of therapeutic agent; Intervention; Joints; Knee; Knee Osteoarthritis; Lead; Lesion; Magnetic Resonance Imaging; Measurement; Measures; Mediating; Medical; Modality; Modeling; Modification; Neck; Osteoarthrosis Deformans; Outcome; Pain; Participant; Physical Function; Placebos; Polyarthritides; Population; Property; Questionnaires; Randomized; Regimen; Replacement Arthroplasty; Research; Resolution; Rheumatoid Arthritis; Sampling; Scanning; Steroids; Structure; Symptoms; Synovitis; Technology; Testing; Time; Triamcinolone; Ultrasonography; Work; bone; bone health; cytokine; disability; experience; functional status; health care service utilization; interest; joint injury; morphometry; protective effect; public health relevance; substantia spongiosa; success

DESCRIPTION (provided by applicant): Knee OA is a painful disabling condition that has major societal impact yet has no disease-modifying therapies. It is, therefore, salient that a rationale exists for OA-modifying effects from intra-articular corticosteroids (IACS). IACS are in clinical use for sporadic knee OA pain flares, but the notion that they might influence OA progression is new, and derives from the recent observation of a high prevalence of synovitis in OA knees. OA synovitis is more focal and less intense than that of systemic polyarthritis, but the profile of cytokine expression is similar and its presence predicts cartilage damage. Corticosteroids reduce progression of joint damage in rheumatoid arthritis, so IACS should also reduce cartilage damage in OA that is mediated by synovitis. Moreover, IACS have protective effects in chemically-induced, mechanically-induced and inflammatory animal models of OA. Our hypothesis is that IACS mitigate inflammatory damage to cartilage and peri-articular bone, and that this benefit outweighs any anti-anabolic effects on these structures. The recent development of quantitative technologies that directly image joint cartilage (MRI), measure subchondral bone properties (DXA and MRI), and evaluate synovitis in a clinical setting (ultrasonography), now allows us to test for the first time the effects of IACS on the structural progression of OA. The overarching goal of this proposed research is to test the potential for disease modification of synovitic knee OA by IACS through a clinical trial directly measuring its effects on cartilage and subchondral bone. We will enroll 140 individuals with knee OA and synovitis (confirmed by ultrasonography), into an adaptive 2-year randomized double-blind clinical trial of intra-articular triamcinolone 40 mg vs. placebo, every 3 months, administered with ultrasound guidance. We will measure changes in cartilage volume, peri-articular bone using MRI and DXA and trabecular morphometry. We will evaluate changes in symptoms, functional status and healthcare utilization using validated questionnaires and objective physical function tests. We will use mixed effects regression models for longitudinal repeated measures to test for a difference in the trajectory of cartilage volume over time between the treatment groups. We will conduct an adaptive interim analysis after the first half of participants has completed the trial. This will allow the trial to be stopped early for either success or futility, or otherwise continue. PUBLIC HEALTH RELEVANCE: Knee OA is a common painful disabling form of arthritis that is a major cause of work-loss and need for joint replacement. There are no medical treatments known to change the rate at which this disease progresses. However, a recent observation that knees with OA that have inflammation are more likely to lose cartilage raises the possibility that injection of corticosteroids (which suppress inflammation) might reduce the rate of cartilage loss and joint damage in these knees. The objective of this research is to test this possibility by performing a clinical trial of corticosteroid injections in knees with OA and inflammation using recently-developed technologies that directly measure changes in knee cartilage and surrounding bone. Confirmation of this hypothesis would lead to an easily-deployable and inexpensive disease-modification strategy for knee OA.

描述（由申请人提供）：膝盖OA是一种痛苦的残疾状况，具有重大的社会影响，但没有改善疾病的疗法。因此，显着的是，关节内皮质类固醇（IACS）的OA修饰作用的基本原理。 IACS用于偶然的膝盖OA疼痛效果，但是它们可能影响OA进展的观念是新的，并且源于最近观察到OA膝盖中滑膜炎的高患病率。 OA滑膜炎比全身性多重关节炎更局灶性，更强烈，但是细胞因子表达的特征相似，其存在预测软骨损伤。皮质类固醇减少类风湿关节炎中关节损伤的进展，因此IACS还应减少由滑膜炎介导的OA的软骨损伤。此外，IACS在化学诱导的，机械诱导的和炎症的OA模型中具有保护作用。我们的假设是，IACS减轻对软骨和关节周围骨骼的炎症损害，并且这种益处大于对这些结构的任何抗生物代谢作用。最新的定量技术的开发直接成像关节软骨（MRI），测量软骨下骨特性（DXA和MRI），并在临床环境（超声检查）中评估滑膜炎，现在使我们能够首次测试IACS对OA结构进展的影响。这项拟议的研究的总体目标是通过一项临床试验直接测量其对软骨和软骨下骨的影响来测试IACS通过临床试验来修改Synovitic膝关节OA的潜力。我们将招募140名膝盖OA和滑膜炎的人（通过超声检查确认），每3个月进行一次适应性的2年随机双盲临床试验，40 mg vs.安慰剂，每3个月进行一次超声指导。 我们将使用MRI和DXA和小梁形态计量的软骨体积，关节骨周围骨的变化。我们将使用经过验证的问卷和客观的身体功能测试评估症状，功能状况和医疗保健利用的变化。我们将使用混合效应回归模型进行纵向重复测量，以测试治疗组之间随时间的软骨体积轨迹的差异。在上半年参与者完成试验后，我们将进行自适应临时分析。这将使试验能够提早停止，以确保成功或徒劳，或者继续进行。 公共卫生相关性：膝关节OA是一种常见的痛苦残疾关节炎形式，是造成工作损害的主要原因，需要关节替代。尚无医疗治疗可以改变这种疾病的发展速度。但是，最近的观察结果是，炎症的膝盖更可能失去软骨，这增加了注射皮质类固醇（抑制炎症）的可能性可能会降低这些膝盖中软骨损失和关节损伤的速度。这项研究的目的是通过使用最近开发的技术直接测量膝盖软骨和周围骨骼的变化，对膝盖和炎症进行皮质类固醇注射的临床试验来测试这种可能性。确认这一假设将导致膝关节OA的易于消除和廉价的疾病修饰策略。