Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis
Dopamine Transporter Neuroimaging as an Enrichment Biomarker in Early Parkinson's Disease Clinical Trials: A Disease Progression Modeling Analysis
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DOI：
10.1111/cts.12492
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发表时间：
2018-01-01
影响因子：
3.9
通讯作者：
Romero, Klaus
中科院分区：
文献类型：
--
作者：
Conrado, Daniela J.;Nicholas, Timothy;Romero, Klaus
鉴于人们认识到疾病修饰疗法应侧重于帕金森病的早期阶段，纯粹基于临床标准的试验招募提出了重大挑战。本文的目标是确定多巴胺转运蛋白神经影像作为早期运动性帕金森病临床试验中富集生物标志物的效用。在线性混合效应模型分析中，利用了帕金森病进展标记计划 (PPMI) 观察性研究和帕金森病研究检查 CEP-1347 试验 (PRECEPT) 临床试验中 672 名早期帕金森病受试者的患者水平纵向数据。在没有多巴胺转运蛋白缺陷证据的情况下，有或没有扫描的受试者之间运动评分恶化的速度在统计学和临床上都是不同的。 24 个月时，生物标志物状态之间运动评分相对基线变化的平均差异为 -3.16（90% 置信区间 [CI] = -0.96 至 -5.42）分。多巴胺转运蛋白成像可以识别运动评分急剧恶化的受试者，从而丰富试验并减少 24% 的样本量。
Given the recognition that disease-modifying therapies should focus on earlier Parkinson's disease stages, trial enrollment based purely on clinical criteria poses significant challenges. The goal herein was to determine the utility of dopamine transporter neuroimaging as an enrichment biomarker in early motor Parkinson's disease clinical trials. Patient-level longitudinal data of 672 subjects with early-stage Parkinson's disease in the Parkinson's Progression Markers Initiative (PPMI) observational study and the Parkinson Research Examination of CEP-1347 Trial (PRECEPT) clinical trial were utilized in a linear mixed-effects model analysis. The rate of worsening in the motor scores between subjects with or without a scan without evidence of dopamine transporter deficit was different both statistically and clinically. The average difference in the change from baseline of motor scores at 24 months between biomarker statuses was -3.16 (90% confidence interval [CI] = -0.96 to -5.42) points. Dopamine transporter imaging could identify subjects with a steeper worsening of the motor scores, allowing trial enrichment and 24% reduction of sample size.