Levy Robert, Deer Timothy R, Poree Lawrence, Rosen Steven M, Kapural Leonardo, Amirdelfan Kasra, Soliday Nicole, Leitner Angela, Mekhail Nagy
Institute for Neuromodulation, Boca Raton, FL, USA.
Center for Pain Relief, Charleston, WV, USA.
Neuromodulation. 2019 Apr;22(3):317-326. doi: 10.1111/ner.12932. Epub 2019 Mar 3.
The spinal cord (SC) response to stimulation has yet to be studied in a pivotal clinical study. We report the study design of an ongoing multicenter, randomized, double-blind, controlled, parallel-arm study of an evoked compound action potential (ECAP) controlled closed-loop spinal cord stimulation (SCS) system, which aims to gain U.S. Food and Drug Administration approval.
This study will enroll 134 SCS candidates with chronic trunk and limb pain from up to 20 United States sites. Subjects are randomized 1:1 to receive ECAP-controlled closed-loop or open-loop, conventional SCS. The primary objective is noninferiority of closed-loop stimulation determined by the proportion of subjects with ≥50% reduction in overall trunk and limb pain and no increase in pain medications at the three-month visit. If noninferiority is met, superiority is tested. In addition, measures recommended by IMMPACT (e.g., pain intensity, functional disability, emotional functioning, quality of life, impression of change, and sleep), neurophysiological properties (e.g., SC activation, conduction velocity, chronaxie, and rheobase), and safety are analyzed.
All approved SCS therapies, regardless of the presence or absence of stimulation induced paresthesias, produce fixed-output stimuli; that is, the energy delivered from the electrode array has a defined output irrespective of the neural response of SC fibers. An SCS system has been developed that directly measures the neurophysiologic activation of the SC to stimulation (i.e., ECAP amplitude) and uses this information in a feedback mechanism to produce closed-loop SCS to maintain optimal and stable activation of the SC. This study represents the first randomized, double-blind, pivotal study in the field of neuromodulation to measure SC activation in ECAP-controlled closed-loop versus open-loop stimulation and is expected to yield important information regarding differences in safety, efficacy, and neurophysiological properties. The potential clinical utility of these objective measurements of SC activation and other neurophysiological properties promises to improve outcomes of SCS for chronic pain patients.
脊髓（SC）对刺激的反应尚未在一项关键的临床研究中得到探究。我们报告了一项正在进行的多中心、随机、双盲、对照、平行组研究的研究设计，该研究针对一种诱发复合动作电位（ECAP）控制的闭环脊髓刺激（SCS）系统，旨在获得美国食品药品监督管理局的批准。
本研究将从美国多达20个地点招募134名患有慢性躯干和肢体疼痛的SCS候选者。受试者按1:1随机分组，接受ECAP控制的闭环或开环、传统SCS。主要目标是通过在三个月随访时总体躯干和肢体疼痛减轻≥50%且止痛药物未增加的受试者比例来确定闭环刺激的非劣效性。如果达到非劣效性，则检验优效性。此外，还分析了IMMPACT推荐的指标（如疼痛强度、功能障碍、情绪功能、生活质量、改善印象和睡眠）、神经生理特性（如脊髓激活、传导速度、时值和基强度）以及安全性。
所有已获批的SCS疗法，无论是否存在刺激诱发的感觉异常，均产生固定输出刺激；也就是说，从电极阵列传递的能量具有确定的输出，而与脊髓纤维的神经反应无关。现已开发出一种SCS系统，该系统可直接测量脊髓对刺激的神经生理激活（即ECAP幅度），并在反馈机制中利用此信息产生闭环SCS，以维持脊髓的最佳和稳定激活。本研究是神经调节领域中第一项随机、双盲、关键研究，旨在测量ECAP控制的闭环刺激与开环刺激中脊髓的激活情况，预计将产生有关安全性、有效性和神经生理特性差异的重要信息。这些脊髓激活和其他神经生理特性的客观测量的潜在临床效用有望改善慢性疼痛患者的SCS治疗效果。
