Abstract：
Bumetanide is a selective NKCC1 chloride importer antagonist which is being repurposed as a mechanism-based treatment for neurodevelopmental disorders (NDDs). Due to their specific actions, these kinds of interventions will only be effective in particular subsets of patients. To anticipate stratified application, we recently completed three bumetanide trials each focusing on different stratification strategies with the additional objective of deriving the most optimal endpoints. Here we publish the protocol of the post-trial access combined cohort study to confirm previous effects and stratification strategies in the trial cohorts and in new participants.
Participants of the three previous cohorts and a new cohort will be subjected to 6 months bumetanide treatment using multiple baseline Single Case Experimental Designs. The primary outcome is the change, relative to baseline, in a set of patient reported outcome measures focused on direct and indirect effects of sensory processing difficulties. Secondary outcome measures include the conventional questionnaires \'social responsiveness scale\', \'repetitive behavior scale\', \'sensory profile\' and \'aberrant behavior scale\'. Resting-state EEG measurements will be performed at several time-points including at Tmax after the first administration. Assessment of cognitive endpoints will be conducted using the novel Emma Tool box, an in-house designed battery of computerized tests to measure neurocognitive functions in children.
This study aims to replicate previously shown effects of bumetanide in NDD subpopulations, validate a recently proposed treatment prediction effect methodology and refine endpoint measurements.
EudraCT: 2020-002196-35, registered 16 November 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002196-35/NL.
Participants of the three previous cohorts and a new cohort will be subjected to 6 months bumetanide treatment using multiple baseline Single Case Experimental Designs. The primary outcome is the change, relative to baseline, in a set of patient reported outcome measures focused on direct and indirect effects of sensory processing difficulties. Secondary outcome measures include the conventional questionnaires \'social responsiveness scale\', \'repetitive behavior scale\', \'sensory profile\' and \'aberrant behavior scale\'. Resting-state EEG measurements will be performed at several time-points including at Tmax after the first administration. Assessment of cognitive endpoints will be conducted using the novel Emma Tool box, an in-house designed battery of computerized tests to measure neurocognitive functions in children.
This study aims to replicate previously shown effects of bumetanide in NDD subpopulations, validate a recently proposed treatment prediction effect methodology and refine endpoint measurements.
EudraCT: 2020-002196-35, registered 16 November 2020, https://www.clinicaltrialsregister.eu/ctr-search/trial/2020-002196-35/NL.
摘要：
布美他尼是一种选择性的NKCC1氯转运蛋白拮抗剂，正被用作神经发育障碍（NDD）的基于机制的治疗方法。由于他们的具体行动，这些干预措施仅对特定的患者子集有效。为了预测分层应用，我们最近完成了三项布美他尼试验,每项试验都集中于不同的分层策略,其额外目标是得出最佳终点.在这里，我们发布了试验后访问组合队列研究的方案，以确认试验队列和新参与者的先前效果和分层策略。
前三个队列和新队列的参与者将使用多个基线单例实验设计进行6个月的布美他尼治疗。主要结果是变化，相对于基线，在一组患者报告的结果测量集中在感觉处理困难的直接和间接影响。次要结果测量包括常规问卷“社会反应量表”，“重复行为量表”，“感官配置文件”和“异常行为量表”。静息状态EEG测量将在几个时间点进行,包括在第一次给药后的Tmax。认知终点的评估将使用新的艾玛工具箱进行，内部设计的一系列计算机化测试，用于测量儿童的神经认知功能。
本研究旨在复制先前显示的布美他尼在NDD亚群中的作用，验证最近提出的治疗预测效果方法，并完善终点测量。
EudraCT：2020-002196-35，注册于2020年11月16日，https://www。临床试验登记。欧盟/ctr-search/trial/2020-002196-35/NL。
前三个队列和新队列的参与者将使用多个基线单例实验设计进行6个月的布美他尼治疗。主要结果是变化，相对于基线，在一组患者报告的结果测量集中在感觉处理困难的直接和间接影响。次要结果测量包括常规问卷“社会反应量表”，“重复行为量表”，“感官配置文件”和“异常行为量表”。静息状态EEG测量将在几个时间点进行,包括在第一次给药后的Tmax。认知终点的评估将使用新的艾玛工具箱进行，内部设计的一系列计算机化测试，用于测量儿童的神经认知功能。
本研究旨在复制先前显示的布美他尼在NDD亚群中的作用，验证最近提出的治疗预测效果方法，并完善终点测量。
EudraCT：2020-002196-35，注册于2020年11月16日，https://www。临床试验登记。欧盟/ctr-search/trial/2020-002196-35/NL。
