Lawson Health Research Institute, London, ON N6C2R5, Canada.
MDDT Inc., London, ON N6G0J3, Canada.
Toxins (Basel). 2020 Dec 20;12(12):807. doi: 10.3390/toxins12120807.
In this first, double-blind, randomized, placebo-controlled exploratory trial, we evaluate the efficacy and safety of incobotulinumtoxinA and feasibility of using kinematic tremor assessment to aid in the planning of muscle selection in a multicenter setting. Reproducibility of the planning technology to other clinical sites was explored. In this trial (NCT02207946), patients with upper-limb essential tremor (ET) were randomized 2:1 to a single treatment cycle of incobotulinumtoxinA or placebo. A tremor kinematic analytics investigational device was used to define a customized muscle set for injection, related to the pattern of the wrist, forearm, elbow, and shoulder tremor for each patient, and the incobotulinumtoxinA dose per muscle (total ≤ 200 U). Fahn-Tolosa-Marin (FTM) Part B motor performance score, Global Impression of Change Scale (GICS), and kinematic analysis-based efficacy evaluations were assessed. Thirty patients were randomized (incobotulinumtoxinA, = 19; placebo, = 11). FTM motor performance scores showed greater improvement with incobotulinumtoxinA versus placebo at Week 4 ( 0.003) and Week 8 ( 0.031). The physician-rated GICS score indicated improvement with incobotulinumtoxinA versus placebo at Week 4 ( < 0.05). IncobotulinumtoxinA also decreased accelerometric hand-tremor amplitude versus placebo from baseline to Week 4 ( 0.004) and Week 8 ( < 0.001), with persistent tremor reduction up to 24 weeks post-injection. IncobotulinumtoxinA produced a slight and transient reduction of maximal grip strength versus placebo; two patients reported localized finger muscle weakness. Customized incobotulinumtoxinA injections decreased tremor severity and improved hand motor function in patients with upper-limb ET after a single injection cycle, with a favorable tolerability profile. The study showed that tremor kinematic analytics technology could be successfully scaled for use in other clinical sites.
在这项首次的、双盲、随机、安慰剂对照的探索性试验中，我们评估了 incobotulinumtoxinA 的疗效和安全性，以及使用运动震颤评估来协助在多中心环境中选择肌肉的可行性。还探索了该规划技术在其他临床地点的可重复性。在这项试验（NCT02207946）中，上肢特发性震颤（ET）患者按 2:1 随机分配至 incobotulinumtoxinA 或安慰剂的单次治疗周期。使用震颤运动分析研究设备来定义针对每个患者手腕、前臂、肘部和肩部震颤模式的定制肌肉集，以及每块肌肉的 incobotulinumtoxinA 剂量（总计≤200U）。采用 Fahn-Tolosa-Marin（FTM）运动表现评分第 B 部分、总体变化印象量表（GICS）和基于运动分析的疗效评估进行评估。30 名患者被随机分配（incobotulinumtoxinA，n=19；安慰剂，n=11）。FTM 运动表现评分显示，与安慰剂相比，incobotulinumtoxinA 在第 4 周（ 0.003）和第 8 周（ 0.031）时的改善更显著。医生评估的 GICS 评分显示，与安慰剂相比，incobotulinumtoxinA 在第 4 周（ <0.05）时的改善更显著。与安慰剂相比，incobotulinumtoxinA 还从基线开始到第 4 周（ 0.004）和第 8 周（ <0.001）时降低了加速度计手部震颤幅度，且注射后 24 周内持续减少震颤。与安慰剂相比，incobotulinumtoxinA 轻微且短暂地降低了最大握力；两名患者报告局部手指肌肉无力。在单次注射周期后，定制的 incobotulinumtoxinA 注射可降低上肢 ET 患者的震颤严重程度并改善手部运动功能，且具有良好的耐受性。该研究表明，震颤运动分析技术可成功扩展用于其他临床地点。
