Novel Stimulation Patterns to Improve the Effectiveness of Spinal Cord Stimulation

提高脊髓刺激有效性的新颖刺激模式

基本信息

批准号：
10358071
负责人：
Rosana Esteller
金额：
$ 105.61万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-07 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10358071
关键词：
Action Potentials Acute Adoption Biometry Clinical Clinical Research Clinical effectiveness Computer software Data Data Collection Development Devices Double-Blind Method Effectiveness Elements Esthesia Evaluation Feasibility Studies Fiber Frequencies Home Hyperalgesia Incidence Institutional Review Boards Intervention Investigation Lead Location Longevity Longterm Follow-up Measurement Medical Modality Morphology Nature Neurons Neurostimulation procedures of spinal cord tissue Numeric Rating Scale Opioid Outcome Outcome Measure Pain Pain Measurement Paresthesia Patients Pattern Phase Physiologic pulse Physiological Randomized Controlled Trials Recovery Refractory Reporting Research Risk Rodent Role Sensory Software Design Software Validation Stimulus Systems Development Technology Testing Time Training Treatment Efficacy Treatment Failure Variant Width allodynia base behavioral response chronic pain chronic pain management chronic pain patient clinical pain digital disability dorsal column first-in-human habituation human study implantable device implantation improved improved outcome innovation novel opioid misuse opioid use pain model pain outcome pain patient pain reduction pain relief porcine model pre-clinical preclinical study randomized controlled design recruit research clinical testing response time use treatment effect treatment responders verification and validation

项目摘要

Project Summary Spinal cord stimulation (SCS) is a nonpharmacological intervention for the treatment of chronic pain. Importantly, SCS may be more effective than opioids for pain relief and has been demonstrated to reduce opioid misuse in pain patients. Current SCS therapy uses time-invariant pulses (TIP), which is based on stimulation with fixed parameter pulse trains. However, SCS based on TIP stimulation has two critical challenges: 1) limited ability to contour the location and quality of the paresthesia coverage and 2) loss of treatment effect due to tolerance. To overcome these challenges, we propose the use of novel stimulation time variant pulse (TVPs) patterns, in which a stimulation parameter changes according to a modulatory time-varying function. TVPs may provide better therapy than TIPs in two ways. First, TVPs can change the recruitment of dorsal column fibers on a pulse by pulse basis in a way impossible via TIPs. Support for this comes from our pilot pre-clinical study in which we demonstrated that TVPs can generate dorsal column evoked compound action potentials (ECAPs) whose morphologies vary with the applied TVPs. Second, the time-varying nature of TVPs may produce better sensory encoding compared to TIPs. Support for this comes from preliminary results from our own and an independent pilot, acute clinical study suggesting that TVPs can produce dynamic, enhanced coverage of the painful region and improved perceived sensations in chronic pain patients. Our central hypotheses is that TVPs can improve outcomes for SCS by enhancing paresthesia coverage and reducing tolerance by varying spatial neuronal recruitment. In this proposal, we will develop devices capable of delivering TVPs and perform long-term clinical testing in chronic pain patients to define the role of TVP SCS in the management of intractable chronic pain. In this study, we will develop the firmware and software to deliver TVPs, and obtain IRB and IDE approval for a clinical study using an implantable pulse generator capable of delivering TVPs (Aim 1/UG3). Then, we will conduct a First in Human feasibility study with a double-blind, randomized-controlled design (Aim 2/UH3), to determine the extent to which SCS TVP can reduce pain and disability.

项目概要脊髓刺激（SCS）是一种治疗慢性疼痛的非药物干预措施。重要的是， SCS 可能比阿片类药物更有效地缓解疼痛，并且已被证明可以减少阿片类药物的滥用疼痛患者。目前的 SCS 疗法使用时不变脉冲 (TIP)，它基于固定脉冲刺激参数脉冲串。然而，基于 TIP 刺激的 SCS 存在两个关键挑战：1）有限的能力勾勒出感觉异常覆盖的位置和质量，以及 2) 由于耐受性而导致的治疗效果丧失。为了克服这些挑战，我们建议使用新颖的刺激时变脉冲（TVP）模式，其刺激参数根据调节时变函数而变化。 TVP 可能会提供在两个方面比 TIP 更好的治疗。首先，TVP 可以改变脉冲上背柱纤维的募集以脉冲为基础，以一种通过 TIP 不可能实现的方式。对此的支持来自我们的试点临床前研究，其中我们证明 TVP 可以产生背柱诱发复合动作电位（ECAP），其形态随所应用的 TVP 的不同而变化。其次，TVP 的时变特性可能会产生更好的感官效果编码与 TIP 的比较。对此的支持来自我们自己和独立机构的初步结果试点急性临床研究表明 TVP 可以对疼痛区域产生动态、增强的覆盖并改善慢性疼痛患者的感知感觉。我们的中心假设是 TVP 可以通过增强感觉异常覆盖率和改善 SCS 的结果通过改变空间神经元募集来降低耐受性。在本提案中，我们将开发能够提供 TVP 并在慢性疼痛患者中进行长期临床测试，以确定 TVP SCS 在治疗中的作用顽固性慢性疼痛的治疗。在本研究中，我们将开发固件和软件来交付 TVP，并获得 IRB 和 IDE 批准使用植入式脉冲发生器进行临床研究交付 TVP（目标 1/UG3）。然后，我们将进行一项双盲的人类首次可行性研究，随机对照设计（目标 2/UH3），以确定 SCS TVP 减轻疼痛和缓解疼痛的程度残疾。