Home-based actigraphy to predict disability progression and enhance clinical trials in multiple sclerosis

家庭体动记录仪可预测残疾进展并加强多发性硬化症的临床试验

• 批准号: 10656583
• 负责人: Ellen M. Mowry
• 金额: $ 67.36万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-07 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656583
• 关键词: Acceleration; Address; Categories; Central Nervous System; Clinical; Clinical Trials; Conduct Clinical Trials; Data; Development; Devices; Diagnosis; Dimensions; Disease; Enrollment; Exclusion; Goals; Home; Image; Immune; Immunotherapy; Injury; Label; Length; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Methods; Multiple Sclerosis; Myelin; Nerve Degeneration; Neurologic; Neurons; Outcome; Outcome Measure; Patient Selection; Patients; Pattern; Persons; Phase; Phenotype; Publishing; Relapsing-Remitting Multiple Sclerosis; Risk; Sample Size; Secondary Progressive Multiple Sclerosis; Standardization; Subgroup; Technology; Therapeutic; Therapeutic Trials; Time; Wrist; actigraphy; brain magnetic resonance imaging; cerebral atrophy; clinical outcome measures; clinical predictors; cohort; disability; disabling symptom; effective therapy; follow-up; improved; middle age; multiple sclerosis patient; phase II trial; phase III trial; primary outcome; therapeutic development

PROJECT SUMMARY/ABSTRACT While effective immunotherapies exist for relapsing-remitting multiple sclerosis (RRMS), therapies for progressive MS are limited. In part, this relates to the fact that progressive MS is caused by gradual loss of central nervous system neurons rather than by immune-mediated injury to the myelin around them. However, therapeutic development has also been hampered by the lack of quality outcome measures of clinical disability progression in MS. The inadequacies of the gold standard, the Expanded Disability Status Scale (EDSS), inflate the sample size and length requirements of progressive MS trials. Further, while clinicians may suspect that a person with RRMS has transitioned to a progressive course (secondary progressive MS), it often takes years to confirm using the EDSS. Thus, these patients, perhaps the most informative with much function to lose, are excluded from progressive MS trials. Phase 2 progressive MS trials often rely on whole brain atrophy, measured by brain magnetic resonance imaging (MRI), as the primary outcome, which also has limitations. Considering several neurodegeneration measures concomitantly may improve the efficiency of such trials. Wearable tri-axial actigraphs are non-invasive, inexpensive devices that measure activity patterns in a home- based, real-world setting. Using our sophisticated analytic approach that incorporates multiple dimensions of activity, we are able to distinguish even small numbers of people with MS based on EDSS score. We propose a longitudinal study of 255 MS patients with confirmed, suspected, or no evident progression, tracking EDSS and actigraphy-derived data for up to 4 years. We will obtain baseline and subsequent brain MRIs and other outcomes traditionally used in progressive MS trials to conduct the following aims: Aim 1. To evaluate if actigraphy-derived measures reliably predict subsequent EDSS-confirmed disability progression in established progressive MS patients. Aim 2. To evaluate if actigraphy-derived measures distinguish RRMS patients with and without suspected progression and predict subsequent risk of EDSS-confirmed disability progression. Aim 3. To evaluate the relative contribution of actigraphy-derived measures, when combined with traditional imaging metrics of neurodegeneration, in predicting subsequent clinical disability change. Corresponding directly to the goal of PA-18-145, this project uses cutting-edge, home-based technology to predict MS patient trajectories. We anticipate that actigraphy measures will predict subsequent worsening on EDSS, particularly in those with definite or suspected MS progression, and that adding actigraphy-based measures to imaging measures of neurodegeneration will improve the prediction of subsequent, EDSS- confirmed disability progression. If correct, actigraphy will revolutionize the conduct of therapeutic trials for progressive MS, a critical step for arresting disability accumulation in this common, devastating disease.

项目摘要/摘要 虽然对复发-缓解型多发性硬化症(RRMS)有有效的免疫疗法，但治疗 进行性多发性硬化症是有限的。在某种程度上，这与进行性多发性硬化症是由逐渐丧失的 中枢神经系统神经元，而不是通过免疫介导性损伤周围的髓鞘。然而， 治疗发展也因缺乏临床残疾的高质量结果衡量标准而受到阻碍。 金标准、扩展残疾状况量表、 扩大进行性多发性硬化症试验的样本量和长度要求。此外，尽管临床医生可能会怀疑 患有RRMS的人已经过渡到进展性疗程(次级进展性MS)，通常需要 使用EDSS进行确认需要数年时间。因此，这些患者可能是信息量最大、功能最多的 失败，被排除在进展性多发性硬化症试验之外。2期进展性多发性硬化症试验通常依赖于全脑萎缩， 以脑部磁共振成像(MRI)作为主要测量结果，也有局限性。 同时考虑几种神经退行性变措施可能会提高此类试验的效率。 可穿戴的三轴活动记录仪是一种非侵入性的、廉价的设备，可以测量家庭中的活动模式- 基于真实世界的环境。使用我们复杂的分析方法，该方法结合了多个维度 根据EDSS评分，我们甚至能够区分出极少数的MS患者。我们 建议对255名确诊、疑似或无明显进展的MS患者进行纵向研究， 跟踪EDSS和动作记录仪派生的数据长达4年。我们将获得基线和后续的大脑 磁共振成像和其他传统上用于渐进式多发性硬化试验的结果，以达到以下目的： 目的1.评估肌动描记测量是否可靠地预测随后的EDSS确认的残疾 已确诊的进展性多发性硬化症患者的进展。 目的2.评估肌动描记测量方法是否能区分有无可疑的RRMS患者 并预测EDSS确认的残疾进展的后续风险。 目的3.评估与传统测量方法相结合时，动作图衍生测量方法的相对贡献 神经退行性变的影像指标，用于预测随后的临床残疾变化。 与PA-18-145的目标直接对应，该项目使用尖端的、基于家庭的技术来 预测MS患者的轨迹。我们预计，动作测量方法将预测随后的恶化 EDSS，特别是在那些确定或怀疑MS进展的人，并增加基于动作图的 对神经退行性变的成像措施将提高对后续EDSS的预测 已确认伤残进展。如果正确，动作记录术将彻底改变治疗试验的进行。 进行性多发性硬化症，这是阻止这种常见的、破坏性的疾病中残疾积累的关键一步。