Wireless transcutaneous electrical stimulation (TENS) for chemotherapy-induced peripheral neuropathy: A phase II randomized clinical trial

项目总结 化疗引起的周围神经病变(CIPN)发生在大约60%的患者中 接受神经毒性化疗药物。CIPN的症状包括灼伤/射击疼痛、刺痛、 抽筋，手脚麻木。CIPN与平衡受损、行走、 睡眠，生活质量下降，摔倒。很少有，只有最低限度有效的治疗方法可用于 CIPN；这些药物治疗很少是基于证据的，潜在的成瘾，和 为综合药房做出贡献。一些研究表明，CIPN是由异常神经元引起的 中枢和外周神经系统的处理，包括中枢下降的减少 抑制机制。数据显示，经皮电神经刺激(TENS)可缓解 其他神经病理性疼痛的症状，部分通过激活中枢下行抑制 但这一机制在CIPN中尚未被研究。拟议的研究 目的是研究TENS的初步疗效，这是一种安全、廉价、非药物治疗的方法 对于CIPN。一项严格的II期、多点、患者和评估者盲法随机临床试验(RCT) 研究生理和心理机制，并利用NCI社区 提出了有效的肿瘤学研究计划(NCORP)。这项研究的目的是获得 为开展验证性、第三阶段随机对照试验提供信息的数据。拟议的TENS设备是一名患者- 受控的无线装置，可方便地在全天进行身体活动时佩戴； 单元是最大限度地提高临床试验依从性和优化临床传播的理想选择 练习一下。这项研究的主要目的是获得初步的疗效估计(效果大小和 CIPN(CIPN20)的综合测量的可信区间)。次要目标包括 获得(1)对个别CIPN症状的初步疗效估计(0-10数值评分 量表)，(2)TENS对CIPN患者活动和平衡的初步疗效，(3)对 TENS关于CIPN患者中枢下行抑制机制的研究，以及(4) 在多站点NCORP研究网络中进行患者和评估者盲目的TENS随机对照试验。 该二期随机对照试验是严格评估疗效的研究计划中不可或缺的一步。 对CIPN来说是十分之一。为CIPN建立有效的非药物治疗将有助于缓解 癌症幸存者的痛苦，同时避免目前许多 现有的止痛药。

PROJECT SUMMARY Chemotherapy-induced peripheral neuropathy (CIPN) occurs in approximately 60% of patients who receive neurotoxic chemotherapy agents. Symptoms of CIPN include burning/shooting pain, tingling, cramping, and numbness in the hands and feet. CIPN is associated with impaired balance, walking, and sleep, decreased quality of life, and falls. Few, only minimally effective treatments are available for CIPN; these pharmacologic treatments are rarely evidenced-based, potentially addictive, and contribute to polypharmacy. Some research suggests that CIPN results from abnormal neuronal processing in the central and peripheral nervous systems, including decreased central descending inhibitory mechanisms. Data suggests that transcutaneous electrical nerve stimulation (TENS) relieves symptoms in other neuropathic pain conditions, partly by activating central descending inhibitory pathways, but this mechanism has yet to be investigated for TENS in CIPN. The proposed research aims to investigate the preliminary efficacy of TENS, a safe, inexpensive, non-pharmacologic treatment for CIPN. A rigorous phase II, multi-site, patient- and assessor-blinded randomized clinical trial (RCT) that investigates physiologic and psychologic mechanisms and leverages the NCI Community Oncology Research Program (NCORP) for efficiency is proposed. The purpose of the study is to obtain data to inform the conduct of a confirmatory, phase III RCT. The proposed TENS device is a patient- controlled, wireless unit that can conveniently be worn throughout the day during physical activity; the unit is ideal for maximizing adherence in clinical trials and for optimizing dissemination in clinical practice. The primary aim of the study is to obtain preliminary efficacy estimates (effect sizes and confidence intervals) of TENS on a composite measure of CIPN (CIPN20). Secondary aims include obtaining (1) preliminary efficacy estimates for individual CIPN symptoms (0 – 10 numeric rating scales), (2) preliminary efficacy of TENS on activity and balance in patients with CIPN, (3) effects of TENS on central descending inhibitory mechanisms in CIPN patients, and (4) feasibility data for conducting a patient- and assessor-blinded RCT of TENS in the multi-site NCORP Research Network. This phase II RCT is an integral step in a program of research that will rigorously evaluate the efficacy of TENS for CIPN. Establishing effective, non-pharmacologic treatments for CIPN will help to mitigate suffering in cancer survivors while avoiding potentially harmful side effects caused by many currently available analgesic drugs.