评估多巴胺转运体成像作为 2 期帕金森病试验中的富集生物标志物。
Evaluating dopamine transporter imaging as an enrichment biomarker in a phase 2 Parkinson's disease trial.
机构信息
Biogen, 300 Binney Street, Cambridge, MA, 02142, USA.
Biogen, Maidenhead, UK.
出版信息
BMC Neurol. 2021 Nov 23;21(1):459. doi: 10.1186/s12883-021-02470-8.
BACKGROUND
Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can quantify the functional integrity of the dopaminergic nerve terminals and has been suggested as an imaging modality to verify the clinical diagnosis of Parkinson's disease (PD). Depending on the stage of progression, approximately 5-15% of participants clinically diagnosed with idiopathic PD have been observed in previous studies to have normal DaT-SPECT patterns. However, the utility of DaT-SPECT in enhancing early PD participant selection in a global, multicenter clinical trial of a potentially disease-modifying therapy is not well understood.
METHODS
The SPARK clinical trial was a phase 2 trial of cinpanemab, a monoclonal antibody against alpha-synuclein, in participants with early PD. DaT-SPECT was performed at screening to select participants with DaT-SPECT patterns consistent with degenerative parkinsonism. Acquisition was harmonised across 82 sites. Images were reconstructed and qualitatively read at a central laboratory by blinded neuroradiologists for inclusion prior to automated quantitative analysis.
RESULTS
In total, 482 unique participants were screened between January 2018 and May 2019; 3.8% (15/398) of imaged participants were excluded owing to negative DaT-SPECT findings (i.e., scans without evidence of dopaminergic deficit [SWEDD]).
CONCLUSION
A smaller proportion of SPARK participants were excluded owing to SWEDD status upon DaT-SPECT screening than has been reported in prior studies. Further research is needed to understand the reasons for the low SWEDD rate in this study and whether these results are generalisable to future studies. If supported, the radiation risks, imaging costs, and operational burden of DaT-SPECT for enrichment may be mitigated by clinical assessment and other study design aspects.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT03318523 . Date submitted: October 19, 2017. First Posted: October 24, 2017.
背景
多巴胺转运体单光子发射计算机断层扫描（DaT-SPECT）可定量评估多巴胺能神经末梢的功能完整性，已被提议作为一种成像方式来验证帕金森病（PD）的临床诊断。在以前的研究中，大约有 5-15%的被临床诊断为特发性 PD 的参与者被观察到 DaT-SPECT 模式正常，这取决于疾病进展的阶段。然而，DaT-SPECT 在增强全球多中心临床试验中对潜在疾病修饰治疗的早期 PD 参与者选择的作用尚不清楚。
方法
SPARK 临床试验是一项针对 cinpanemab（一种针对α-突触核蛋白的单克隆抗体）的 2 期临床试验，入组了早期 PD 患者。在筛选时进行 DaT-SPECT 以选择 DaT-SPECT 模式与退行性帕金森病一致的参与者。在 82 个地点进行了采集的协调。由盲法神经放射科医生对图像进行重建和定性解读，以纳入自动定量分析之前。
结果
在 2018 年 1 月至 2019 年 5 月期间，共筛选了 482 名独特的参与者；由于 DaT-SPECT 检查结果阴性（即无多巴胺能缺陷扫描[SWEDD]），有 3.8%（15/398）的成像参与者被排除。
结论
在 DaT-SPECT 筛查时，由于 SWEDD 状态而被排除的 SPARK 参与者比例低于以前的研究报告。需要进一步研究以了解本研究中 SWEDD 率低的原因，以及这些结果是否可推广到未来的研究中。如果得到支持，DaT-SPECT 用于富集的辐射风险、成像成本和操作负担可能会因临床评估和其他研究设计方面而减轻。
试验注册
ClinicalTrials.gov 标识符：NCT03318523。提交日期：2017 年 10 月 19 日。首次提交：2017 年 10 月 24 日。
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