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

• 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
• 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

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.

项目摘要 脊髓刺激（SCS）是用于治疗慢性疼痛的非药物干预措施。重要的是， SC可能比阿片类药物更有效，以缓解疼痛，并已被证明可以减少阿片类药物的滥用 疼痛患者。当前的SC疗法使用时间不变的脉冲（TIP），该脉冲基于固定的刺激 参数脉冲列车。但是，基于小费刺激的SCS面临两个关键挑战：1）有限的能力 轮廓异常覆盖的位置和质量和2）由于耐受性而导致的治疗效果的丧失。 为了克服这些挑战，我们提出了新型刺激时间变体脉冲（TVPS）模式的使用 刺激参数会根据调制时间变化函数而变化。 TVP可以提供 通过两种方式，比技巧更好。首先，TVP可以更改脉冲上背侧柱纤维的募集 通过脉冲基础，通过提示不可能。对此的支持来自我们的试点临床前研究 证明TVP可以生成背侧柱唤起复合动作电位（ECAPS） 形态随施加的TVP而异。其次，TVP的时变性质可能会产生更好的感觉 与技巧相比，编码。对此的支持来自我们自己和独立的初步结果 飞行员，急性临床研究表明，TVP可以产生动态，增强的疼痛区域覆盖范围 并改善了慢性疼痛患者的感知感觉。 我们的核心假设是，TVP可以通过增强感觉异常覆盖范围和 通过不同的空间神经元募集来降低耐受性。在此提案中，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，以定义TVP SC的作用 顽固性慢性疼痛的管理。在这项研究中，我们将开发固件和软件以交付 TVP，并使用能够植入脉冲发生器获得IRB和IDE批准进行临床研究 提供TVPS（AIM 1/UG3）。然后，我们将以双盲，双盲，第一次进行人类可行性研究 随机控制设计（AIM 2/UH3），以确定SCS TVP可以减轻疼痛和 残疾。