Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials
Predicting disease progression in progressive supranuclear palsy in multicenter clinical trials
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DOI：
10.1016/j.parkreldis.2016.04.014
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发表时间：
2016-07-01
影响因子：
4.1
通讯作者：
Boxer, Adam L.
中科院分区：
文献类型：
--
作者：
Bang, Jee;Lobach, Iryna V.;Boxer, Adam L.
简介：临床和 MRI 测量可以追踪 PSP 的疾病进展，但许多测量尚未在多中心临床试验中得到广泛评估。我们在多中心 PSP 试验中确定了捕捉临床衰退和预测疾病进展的最佳措施。方法：使用达武奈肽治疗 PSP 的国际 2/3 期临床试验（意向治疗人群，n = 303）的纵向临床评级量表、神经心理学测试评分和体积 MRI 数据来确定效应量最大、与临床变化最强相关性以及最佳预测能力的测量值 通过 PSP 评定量表 (PSPRS) 测量，一年内辍学或临床衰退。结果：通过可重复电池评估神经心理状态 (RBANS) 测量的基线认知与损耗相关，但影响很小。 PSPRS 和临床总体印象 (CGI) 在测量变化方面具有最大的效应量。 CGI、RBANS、颜色轨迹以及 MRI 中脑和脑室体积的年度变化与年度 PSPRS 相关性最强，并且对于检测年度变化具有最大的效应大小。在基线时，较短的病程、较严重的抑郁症以及 RBANS 和执行功能测试的较低表现与完成者的 PSPRS 更快恶化有关。包括辍学者在内，SEADL、RBANS 和执行功能测试对 PSPRS 的变化轨迹有显着影响。结论：基线认知状态和情绪影响 PSI' 的疾病进展率。多项临床、神经心理学和体积 MRI 测量对 PSP 一年内的变化敏感，适合用于多中心临床试验。 (C) 2016 Elsevier Ltd. 保留所有权利。
Introduction: Clinical and MRI measurements can track disease progression in PSP, but many have not been extensively evaluated in multicenter clinical trials. We identified optimal measures to capture clinical decline and predict disease progression in multicenter PSP trials.Methods: Longitudinal clinical rating scales, neuropsychological test scores, and volumetric MRI data from an international, phase 2/3 clinical trial of davunetide for PSP (intent to treat population, n = 303) were used to identify measurements with largest effect size, strongest correlation with clinical change, and best ability to predict dropout or clinical decline over one year as measured by PSP Rating Scale (PSPRS).Results: Baseline cognition as measured by Repeatable Battery for Assessing Neuropsychological Status (RBANS) was associated with attrition, but had only a small effect. PSPRS and Clinical Global Impression (CGI) had the largest effect size for measuring change. Annual change in CGI, RBANS, color trails, and MRI midbrain and ventricular volumes were most strongly correlated with annual PSPRS and had the largest effect sizes for detecting annual change. At baseline, shorter disease duration, more severe depression, and lower performance on RBANS and executive function tests were associated with faster worsening of the PSPRS in completers. With dropouts included, SEADL, RBANS, and executive function tests had significant effect on PSPRS trajectory of change.Conclusion: Baseline cognitive status and mood influence the rate of disease progression in PSI'. Multiple clinical, neuropsychological, and volumetric MRI measurements are sensitive to change over one year in PSP and appropriate for use in multicenter clinical trials. (C) 2016 Elsevier Ltd. All rights reserved.