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: 10417231
• 负责人: Ellen M. Mowry
• 金额: $ 68.11万
• 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/10417231
• 关键词: Address; Categories; Clinical; Clinical Trials; Conduct Clinical Trials; Data; Development; Devices; Diagnosis; Dimensions; Disease; Enrollment; Goals; Gold; Home; Image; Immune; Immunotherapy; Injury; Label; Length; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Methods; Multiple Sclerosis; Myelin; Nerve Degeneration; Neuraxis; Neurologic; Neurons; Outcome; Outcome Measure; Patient Selection; Patients; Pattern; Persons; Phase; Phase II/III Trial; Phenotype; Publishing; Relapsing-Remitting Multiple Sclerosis; Risk; Sample Size; Secondary Progressive Multiple Sclerosis; Standardization; Subgroup; Technology; Therapeutic; Therapeutic Trials; Time; Wrist; actigraphy; base; brain magnetic resonance imaging; cerebral atrophy; clinical outcome measures; cohort; disability; disabling symptom; effective therapy; follow-up; improved; middle age; multiple sclerosis patient; multiple sclerosis treatment; 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 虽然存在有效的免疫疗法用于复发多发性硬化症（RRMS），但 进行性MS有限。在某种程度上，这与渐进式MS是由于逐渐损失引起的事实 中枢神经系统神经元，而不是免疫介导的损伤对它们周围的髓磷脂。然而， 缺乏临床残疾的质量结果指标也阻碍了治疗性发育 MS的进展。黄金标准的不足，扩展的残疾状况量表（EDSS）， 膨胀样本量和进行性MS试验的长度要求。此外，虽然临床医生可能会怀疑 患有RRM的人已经过渡到渐进式课程（次要渐进式MS），通常需要 使用EDSS确认多年。因此，这些患者，也许是最有用的，功能很大 损失被排除在进步的MS试验之外。第2阶段进行性MS试验通常依赖整个大脑萎缩， 通过大脑磁共振成像（MRI）作为主要结果，它也有局限性。 考虑几种神经退行性措施，可能会提高此类试验的效率。 可穿戴的三轴动作法是无创，廉价的设备，可在家中测量活动模式 基于现实世界的设置。使用我们复杂的分析方法，该方法结合了多个维度 活动，我们甚至可以根据EDSS得分来区分MS的少数人。我们 提出了一项纵向研究，对255名MS患者的患者进行了确认，可疑或没有明显进展的患者 跟踪EDSS和Actraphy衍生的数据长达4年。我们将获得基线和随后的大脑 MRI和其他传统上的结果进行了渐进的MS试验，以执行以下目的： 目的1。评估目录的衍生措施是否可靠地预测随后的EDSS确认残疾 已建立的渐进式MS患者的进展。 目的2。评估行动学位衍生的措施是否区分有或没有怀疑的RRMS患者 进展并预测EDSS确认的残疾进展的风险。 目标3。与传统相结合时，评估行为衍生措施的相对贡献 神经退行性的成像指标，可预测随后的临床残疾变化。 直接与PA-18-145的目标相对应，该项目使用尖端的家庭技术来 预测MS患者轨迹。我们预计，动作措施将预测随后的恶化 EDS，尤其是在具有确定或怀疑MS进展的人中，以及添加基于Attraphy的MS的进展 神经退行性成像度量的措施将改善随后的预测，EDSS- 确认的残疾进展。如果正确的话，Actraphy将彻底改变治疗试验的行为 进行性MS，这是在这种常见的毁灭性疾病中阻止残疾积累的关键步骤。