UNC/NC State Joint Department of Biomedical Engineering, North Carolina State University, Raleigh, North Carolina, USA, Closed-Loop Engineering for Advanced Rehabilitation Research Core, North Carolina State University, Raleigh, North Carolina, USA, Department of Physical Medicine & Rehabilitation, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
Shirley Ryan AbilityLab, Arms + Hands Lab, Chicago, IL, USA.
J Stroke Cerebrovasc Dis. 2022 Oct;31(10):106724. doi: 10.1016/j.jstrokecerebrovasdis.2022.106724. Epub 2022 Aug 30.
The goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors.
A randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression.
89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial.
Use of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance.
Clinical Trial number: NCT02418949.
本研究旨在探讨抗血清素能药物盐酸赛庚啶（HCl）的给药和剂量如何影响脑卒中幸存者痉挛性和弛缓性手部的不随意肌肉张力过高。
这是一项作为更大规模临床试验组成部分的随机、双盲、安慰剂对照的纵向干预研究。94 名患有慢性严重手部障碍的脑卒中幸存者，根据 Chedoke-McMaster 脑卒中评估手部阶段量表（CMSA-H）评定为 2 级或 3 级，采用区组随机分组，分别接受赛庚啶 HCl 剂量或匹配剂量的安慰剂。3 周内剂量从每日 2 次、每次 4 毫克增加至每日 3 次、每次 8 毫克。在基线和每 3 周干预后评估结局。主要结局测量指标为握持终止时间；其他测量指标包括肌肉力量、痉挛、食指长屈肌的共同激活以及记录嗜睡和抑郁等潜在不良反应。
89 名参与者（赛庚啶 HCl 组 44 名，安慰剂组 45 名）完成了研究。与安慰剂组相比，赛庚啶 HCl 组的握持终止时间显著缩短（p<0.05）。仅在 4mg BID 剂量的第一周，赛庚啶 HCl 组就观察到显著的变化（45%时间减少）。对于基线时手部功能障碍更严重（CMSA-H 2 级）的赛庚啶 HCl 组参与者，效果更为明显。相反，对于痉挛（p=0.6）或共同激活（p=0.53），组间交互作用的影响没有显著差异。在试验过程中，力量（p=0.234）或抑郁（p=0.441）均无显著变化。
赛庚啶 HCl 的使用与手指屈肌放松时间的显著缩短相关，而不影响自愿力量，尽管痉挛和共同激活没有改变。减少不随意屈肌活动的持续时间可以促进物体释放和重复抓握任务的完成。
临床试验编号：NCT02418949。
