Accelerating Osteoarthritis Clinical Trials Through Responsive Low-Dose Standing CT Imaging

通过响应性低剂量站立 CT 成像加速骨关节炎临床试验

• 批准号: 9761981
• 负责人: Neil A Segal
• 金额: $ 19.52万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-15 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761981
• 关键词: 3-Dimensional; Address; Adult; Affect; Aging; American; Area; Arthritis; Background Radiation; Biological Markers; Cartilage; Clinic; Clinical; Clinical Research; Clinical Trials; Data; Degenerative polyarthritis; Detection; Diagnostic; Diagnostic radiologic examination; Disease; Disease Progression; Dose; Evaluation; Exhibits; FDA approved; Face; Future; Health; Health Expenditures; Image; Implant; Industry; Intervention; Intervention Trial; Joints; Knee; Knee Osteoarthritis; Knee joint; Lesion; Long-Term Effects; Lower Extremity; Magnetic Resonance Imaging; Measurement; Measures; Medical; Meniscus structure of joint; Metals; Monitor; Morphology; Obesity; Operative Surgical Procedures; Outcome; Pain; Participant; Pathway interactions; Patient Care; Patient Outcomes Assessments; Patient imaging; Patients; Performance; Physical Function; Prevalence; Prevention; Prevention therapy; Process; Radiation; Radiation exposure; Research; Research Personnel; Risk; Roentgen Rays; Sample Size; Scanning; Severity of illness; Standardization; Structure; Symptoms; Therapeutic Effect; Three-Dimensional Imaging; Time; Translating; Treatment Efficacy; Weight-Bearing state; Width; X-Ray Computed Tomography; base; biomarker validation; bone; clinical care; clinically relevant; cohort; cost; disability; effective therapy; follow-up; imaging biomarker; improved; joint injury; knee pain; novel; outcome forecast; prognostic; prognostic value; response; standard care; therapeutic development; therapy development; treatment strategy

Project Summary/Abstract The long-term objective of this research is to enable more affordable and shorter duration clinical trials, thereby facilitating the introduction of effective disease modifying therapies for knee osteoarthritis (OA). OA affects over 27 million Americans, afflicting them with pain, substantial mobility limitations, and large health care expenditures. There are gaps in our ability to predict and detect progression, limiting the potential to forestall this prevalent disease. The critical barriers to determining prognosis and longitudinally monitoring knee OA are the poor sensitivity and responsiveness of radiographs, the most common means of evaluating knee OA. At times, these limitations have made advancement of novel treatments prohibitively expensive, through necessitating large sample sizes and long durations of follow-up for clinical studies. Our preliminary studies established the feasibility of detecting key knee OA features accurately and reliably with standing CT (SCT) imaging. In the proposed project, we will establish the performance of more useful biomarkers for OA than are available with radiographs. We propose to address the remaining steps necessary to begin qualification of these SCT-based OA biomarkers. Aim 1 is to determine the responsiveness of SCT biomarkers for detecting knee OA progression, and to establish concurrent validity through comparison with worsening of cartilage on MRI. Aim 2 is to quantify the added prognostic value of more sensitive detection of meniscal extrusion for prediction of rapid worsening of cartilage lesions and knee pain. Achieving these aims will be transformative; introducing more sensitive and responsive biomarkers for assessing OA, without significantly increasing the cost, time or radiation exposure. The ability to detect structural changes in bone and menisci earlier in the disease process could accelerate scientific progress and clinical care. The enhanced performance could identify stages when patients are most likely to respond to interventions. The expected product will be immediate delivery of substantially improved biomarkers for detection and longitudinal evaluation of OA, that could be deployed in clinical trials, using a compact scanner with the same Relative Radiation Level as radiographs. The enhanced ability to predict and measure OA progression will address critical barriers to progress in OA research and patient care by enabling more efficient assessment of therapeutic efficacy. Designation of OA as a serious disease is opening expedited pathways to approval of OA therapies, making this research timely. The long-term impact of this project will be a potential shift in clinical trials and care— replacement of radiographs for monitoring of knee OA. This research will catalyze the ability to predict and monitor knee OA worsening, enabling more rapid development of therapies by reducing the required sample sizes, duration and costs of clinical trials, thereby powerfully influencing prevention and treatment.

项目概要/摘要 这项研究的长期目标是实现更实惠、持续时间更短的临床试验， 从而促进针对膝骨关节炎（OA）引入有效的疾病修饰疗法。 骨关节炎影响着超过 2700 万美国人，让他们遭受疼痛、严重的行动限制和大面积的疼痛。 医疗保健支出。我们预测和检测进展的能力存在差距，限制了 预防这种流行疾病的潜力。确定预后和治疗的关键障碍 纵向监测膝关节 OA 的缺点是放射线照片的敏感性和反应性较差，最 评估膝关节 OA 的常用方法。有时，这些限制促进了新颖的进步 由于需要大样本量和长时间的随访，治疗费用极其昂贵 用于临床研究。我们的初步研究确立了检测关键膝关节 OA 特征的可行性 通过站立 CT (SCT) 成像准确可靠。在拟议的项目中，我们将建立 与射线照片相比，可提供更有用的 OA 生物标志物。我们建议解决 开始鉴定这些基于 SCT 的 OA 生物标志物所需的其余步骤。目标 1 是 确定 SCT 生物标志物对检测膝关节 OA 进展的反应性，并建立 通过与 MRI 上软骨恶化进行比较来验证同时有效性。目标 2 是量化 更灵敏地检测半月板挤压，以预测快速发生的情况，增加了预后价值 软骨损伤和膝盖疼痛恶化。实现这些目标将带来变革；介绍 用于评估 OA 的更敏感和反应更快的生物标志物，而不显着增加成本， 时间或辐射暴露。能够在早期检测骨骼和半月板的结构变化 疾病过程可以加速科学进步和临床护理。增强的性能可以 确定患者最有可能对干预措施做出反应的阶段。预期的产品将是 立即提供显着改善的生物标志物，用于 OA 的检测和纵向评估， 可以部署在临床试验中，使用具有相同相对辐射水平的紧凑型扫描仪 放射线照片。预测和测量 OA 进展的能力增强将解决关键障碍 通过更有效地评估治疗效果，在 OA 研究和患者护理方面取得进展。 将 OA 指定为严重疾病，为 OA 疗法的批准开辟了快速途径，使得 这项研究很及时。该项目的长期影响将是临床试验和护理的潜在转变—— 替代X光片来监测膝关节骨关节炎。这项研究将促进预测和 监测膝关节 OA 的恶化情况，通过减少所需的治疗来加快治疗的开发 临床试验的样本量、持续时间和成本，从而有力地影响预防和治疗。