High-Resolution, Spinal Cord Stimulation for Non-Opioid Treatment of Neuropathic Pain

高分辨率脊髓刺激用于非阿片类药物治疗神经性疼痛

• 批准号: 10778743
• 负责人: Bryan L McLaughlin
• 金额: $ 14.23万
• 依托单位: MICRO-LEADS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10778743
• 关键词: Action Potentials; Acute; Animals; Back; Cadaver; Capital; Chronic; Clinical; Clinical Trials; Computer software; Contracts; Dependence; Development; Device Designs; Device or Instrument Development; Devices; Electric Stimulation; Electrodes; Electromyography; Electronics; Electrophysiology (science); Employment; Ensure; Etiology; Family Felidae; Feasibility Studies; Feedback; Fiber; Foot Pain; Geometry; High Prevalence; Human; Implant; Inguinal region; Injury; Institutional Review Boards; Intractable Pain; Label; Lateral; Lead; Letters; Limb structure; Longevity; Longitudinal Studies; Lower Extremity; Manufacturer; Maps; Measures; Mechanics; Medial; Medical center; Mental Depression; Mental Health; Morbidity - disease rate; Nerve Root Compressions; Neurostimulation procedures of spinal cord tissue; Operative Surgical Procedures; Opiate Addiction; Opioid; Overdose; Pain; Paralysed; Patients; Performance; Persons; Phase; Physiologic pulse; Positioning Attribute; Protocols documentation; Quality of life; Resolution; Risk; Running; Safety; Shapes; Sheep; Small Business Innovation Research Grant; Specificity; Spinal; Spinal Cord; Spinal Ganglia; Sterilization; Structure; Suicide; Technology; Testing; Thick; Tissues; Validation; Vertebral column; Width; Work; Writing; addiction; biomaterial compatibility; chronic neuropathic pain; chronic pain; cognitive function; commercialization; debilitating pain; design; design verification; dorsal column; dorsal horn; human subject; improved; knee pain; manufacture; meetings; neural; non-opioid analgesic; novel; operation; opioid abuse; opioid use; pain reduction; pain relief; painful neuropathy; pilot test; prescription opioid; programs; safety study; safety testing; spinal nerve posterior root; success; wireless

In this SBIR FastTrack proposal, Micro-Leads will develop HD64—a high-resolution, 64- channel spinal cord stimulation therapy to provide more pain relief with greater specificity for those suffering from chronic neuropathic pain and opioid dependence. Over 25 million in the U.S. suffer from debilitating pain in the trunk and extremities and 55% depend on opioids to ease their suffering. Opioid abuse has claimed the lives of over 200,000 over the past decade and has resulted in devastating reductions in quality of life, in ability to work, and in mental health for the living. Spinal cord stimulation (SCS) has provided pain relief for 60% of those with chronic extremity pain and eliminated opioid use entirely in more than 50%. Despite these advantages, SCS has had a limited success treating isolated pain of the knee, foot, groin, or low-back. The lateral positioned fibers of the spinal cord (ex. the dorsal root entry zone and dorsal horn) represent a more selective neural targeting opportunity yet current, implantable plate-type surgical leads are too rigid and bulky to access these fibers without a significant risk of paralysis or nerve root compression. HD64 provides an ultra-thin and conformal blanket of stimulation contacts across the entire width of the spinal cord. Active-lead technology embeds a tiny electronic chip within the surgical lead and doubles the number of therapy contacts compared with current technology without increasing the number of lead-wires. Collectively, these features improve therapy and simplify surgical workflow. A novel Active-Lead Controller Implantable Pulse Generator (AL-IPG) powers the chip safely, synchronizes with the active-lead electronics, configures the 8 programmable “therapy groups”, and ensures therapy pulses are delivered to the tissue. HD64 therapy is a highly significant, novel solution for the treatment of patients suffering from chronic pain and opioids. PHASE 1: A cadaveric pilot run followed by a non-significant risk intraoperative study (n=6) will be performed to inform the geometric and electrophysiological design parameters of high-resolution HD64 arrays. The study will evaluate activation of medial and lateral spinal targets as measured by intraoperative neuromonitoring of electromyography. At the end of Phase 1, the clinical feasibility of HD64 surgical leads will be established. PHASE 2: In Phase 2, we have HD64 active leads assembled by a GMP manufacturer. We will develop an external Active Lead Pulse Generator and charger which will be submitted for IDE approval. We will perform an Early Feasibility Study Human Trial using active HD64 and AL-IPG hardware (n=10 subjects, n=23 therapy groups, n=2 waveforms). During Phase 2, we will also perform mechanical and electrical design verification testing and chronic safety studies in large animals to demonstrate functional performance to inform the final device. By the end of Phase 2, we will have completed all necessary tasks to inform the final device design and to enable follow-on implanted longitudinal studies of chronic pain and opioid reduction.

在此 SBIR FastTrack 提案中，Micro-Leads 将开发 HD64——一种高分辨率、64 位 通道脊髓刺激疗法可为患者提供更特异性的疼痛缓解 美国有超过 2500 万人患有慢性神经性疼痛和阿片类药物依赖。 躯干和四肢都有疼痛，55% 的人依赖阿片类药物来缓解阿片类药物滥用带来的痛苦。 过去十年中，超过 200,000 人的生命受到影响，并导致生活质量和能力的毁灭性下降 脊髓刺激 (SCS) 已帮助 60% 的人缓解疼痛。 尽管有这些优点，但 50% 以上的患有慢性四肢疼痛的患者完全不再使用阿片类药物。 SCS 在治疗膝盖、足部、腹股沟或腰部的孤立疼痛方面取得了有限的成功。 脊髓纤维（例如背根进入区和背角）代表更具选择性的神经靶向 目前的机会是，植入式板式手术导线过于坚硬且笨重，无法在不接触这些纤维的情况下接入这些纤维。 瘫痪或神经根受压的显着风险。 HD64 在整个宽度上提供超薄且保形的刺激接触毯 脊髓主动引线技术将微型电子芯片嵌入手术引线内，并使数量增加了一倍。 与当前技术相比，在不增加导联线数量的情况下减少了治疗触点的数量。 这些功能改善了治疗并简化了手术流程。新型主动引线控制器植入式。 脉冲发生器 (AL-IPG) 为芯片安全供电，与有源引线电子设备同步，配置 8 可编程“治疗组”，并确保将高治疗脉冲传递到组织。 用于治疗患有慢性疼痛和阿片类药物的患者的重要、新颖的解决方案。 第 1 阶段：将进行尸体试运行，然后进行非重大风险的术中研究 (n=6) 旨在了解高分辨率 HD64 阵列的几何和电生理学设计参数。 该研究将评估术中测量的内侧和外侧脊柱目标的激活 肌电图神经监测 在第一阶段结束时，HD64 手术导线的临床可行性将得到证实。 第 2 阶段：在第 2 阶段，我们将由 GMP 制造商组装 HD64 有源引线。 开发外部有源引线脉冲发生器和充电器，并将其提交给 IDE 批准。 使用主动 HD64 和 AL-IPG 硬件进行早期可行性研究人体试验（n=10 名受试者，n=23 治疗组，n=2 个波形）在第 2 阶段，我们还将进行机械和电气设计。 在大型动物中进行验证测试和长期安全性研究，以证明功能性能以提供信息 在第 2 阶段结束时，我们将完成通知最终设备的所有必要任务。 设计并实现慢性疼痛和阿片类药物减少的后续植入纵向研究。

项目成果

A Systematic Review of Deep Brain Stimulation Targets for Obsessive Compulsive Disorder.

强迫症深部脑刺激目标的系统回顾。

• DOI: 10.1093/neuros/nyaa249
• 发表时间: 2020
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Raviv,Nataly;Staudt,MichaelD;Rock,AndrewK;MacDonell,Jacquelyn;Slyer,Julia;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG

Rapid Visualization Tool for Intraoperative Dorsal Column Mapping Triggered by Spinal Cord Stimulation in Chronic Pain Patients.

用于慢性疼痛患者脊髓刺激触发的术中背柱测绘的快速可视化工具。

• DOI: 10.1109/embc46164.2021.9630459
• 发表时间: 2021
• 期刊: Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
• 作者: Telkes,Ilknur;Behal,Aditya;Hadanny,Amir;Olmsted,ZacharyT;Chitnis,Girish;McLaughlin,Bryan;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG

In Reply: A Systematic Review of Deep Brain Stimulation Targets for Obsessive-Compulsive Disorder.

答复：强迫症深部脑刺激目标的系统回顾。

• DOI: 10.1093/neuros/nyab010
• 发表时间: 2021
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Hadanny,Amir;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Deep Brain Stimulations for Obsessive-Compulsive Disorder: Update of the 2014 Guidelines.

神经外科医生大会强迫症深部脑刺激系统审查和循证指南：2014 年指南更新。

• DOI: 10.1093/neuros/nyaa596
• 发表时间: 2021
• 期刊: Neurosurgery
• 影响因子: 4.8
• 作者: Staudt,MichaelD;Pouratian,Nader;Miller,JonathanP;Hamani,Clement;Raviv,Nataly;McKhann,GuyM;Gonzalez-Martinez,JorgeA;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG

Investigation of the intraoperative cortical responses to spinal motor mapping in a patient with chronic pain.

慢性疼痛患者术中皮质对脊髓运动标测反应的调查。

• DOI: 10.1152/jn.00221.2023
• 发表时间: 2023
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Berwal,Deepak;Telkes,Ilknur;Agarwal,Shruti;Paniccioli,Steven;McCarthy,Kevin;DiMarzio,Marisa;McLaughlin,Bryan;Pilitsis,JulieG
• 通讯作者: Pilitsis,JulieG