Peripheral nerve stimulation for amputee pain

周围神经刺激治疗截肢者疼痛

• 批准号: 9345091
• 负责人: Joseph Wilder Boggs
• 金额: $ 81.38万
• 依托单位: SPR THERAPEUTICS, LLC
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-15 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9345091
• 关键词: Activities of Daily Living; Adopted; Adoption; Amputation; Amputees; Charge; Chronic; Clinic; Clinical; Clinical Research; Clinical Trials; Development; Electric Stimulation Therapy; Electrodes; Ensure; Failure; Fiber; Fracture; Goals; Head; Hip Joint; Home environment; Incidence; Individual; Intractable Pain; Intuition; Lead; Left; Limb structure; Mental Depression; Methods; Molds; Nerve; Operative Surgical Procedures; Pain; Pain management; Patients; Peripheral Nerve Stimulation; Persons; Phase; Physicians; Physiologic pulse; Pilot Projects; Process; Production; Quality Control; Quality of life; Readiness; Risk; Specialist; Steel; Study Section; Sustainable Development; System; Testing; Thinness; Time; Training; Ultrasonography; United States; advanced system; clinically significant; commercialization; design; disability; experience; flexibility; high risk; implantation; improved; large scale production; migration; novel; phase 1 study; post-amputation pain; programs; residual limb; risk minimization; success; tool; verification and validation

Abstract: The goal of the presently proposed Commercialization Readiness Pilot (CRP) Program project is to prepare for commercialization of an implantable system (developed in Phase II) that is capable of delivering a novel peripheral nerve stimulation (PNS) therapy shown to be highly effective in treating intractable pain in a majority of amputees in previous studies (including Phase I). Approximately 1.8 million individuals in the U.S. are living with an amputation, and about 185,000 individuals undergo an amputation each year. Post- amputation pain has a high incidence (95%) and frequently causes further disability, depression, and reductions in quality of life. Existing long-term pain therapies are inadequate long-term and are expensive (totaling up to $2.7-13 Billion/year in the U.S.). The previous Phase I project successfully demonstrated the feasibility of relieving post-amputation pain in 88% of subjects during in-clinic testing with a method of peripheral nerve stimulation (PNS) that selectively activates target fibers using a single electrode inserted remote from the nerve. In an additional 2-wk home trial of temporary percutaneous stimulation, all subjects that completed the trial experienced clinically significant pain relief (average=76%) while receiving 24hr/day stimulation, confirming that pain relief can be sustained as long as stimulation is delivered. The Phase II project is in the final year of the early-stage development of an implantable pulse generator (IPG) designed to be capable of delivering the novel PNS therapy long-term for post-amputation pain relief. The therapy is designed to use a flexible, self-anchoring electrode that avoids the need for open surgery and precise lead placement, and minimizes the risk of complications (fracture & migration) that previously limited use of existing PNS systems. These risks are further reduced by an IPG that is sufficiently thin to be placed in the residual limb, eliminating the need for the lead to cross the hip joint and avoiding the repeated flexing and bending that frequently causes failures with existing commercial systems. The proposed CRP project is needed to advance the system from an early stage (Phase II) to its final late- stage (commercial) design to enable rapid clinical adoption among pain physicians by enhancing the system implantation tools (Aim 1) to reduce complexity and the need for support staff, while leveraging a familiar procedural approach in which the vast majority of these physicians are already proficient. The project is also needed to advance system production from early-stage (intended in the Phase II project for low-volumes in which each IPG is manufactured by skilled technicians in a time-intensive process) to late-stage development of sustainable, quality controlled, high volume production in line with Good Manufacturing Practices (GMP) to enable successful commercialization. Each aim will be considered successful if all verification/validation tests are passed. If successful, the final product will have the potential to meet the needs of amputees and their physicians through a commercially viable and sustainable therapy following FDA approval.

翻译后摘要：目前提出的商业化准备试点（CRP）计划项目的目标是 准备商业化的植入式系统（在第二阶段开发），能够提供 一种新的外周神经刺激（PNS）疗法被证明在治疗顽固性疼痛方面非常有效， 大多数截肢者在以前的研究（包括第一阶段）。在美国大约有180万人。 每年有大约185，000人接受截肢手术。后 截肢疼痛的发生率很高（95%），并经常导致进一步的残疾，抑郁， 生活质量下降。现有的长期疼痛疗法不足以长期且昂贵 （在美国总计高达27 - 130亿美元/年）。 之前的I期项目成功证明了缓解截肢后疼痛的可行性， 88%的受试者在使用周围神经刺激（PNS）方法进行的诊所内测试中选择性 使用远离神经插入的单个电极激活目标纤维。在另一项为期2周的家庭试验中， 在暂时性经皮刺激中，所有完成试验的受试者均发生了具有临床意义的 接受24小时/天刺激时疼痛缓解（平均=76%），证实疼痛缓解可持续， 只要刺激被传递。第二阶段的项目是在最后一年的早期发展阶段， 植入式脉冲发生器（IPG）设计为能够长期提供新型PNS治疗， 缓解截肢后疼痛该疗法被设计为使用柔性的自锚定电极， 需要开放手术和精确的导线放置，并最大限度地减少并发症的风险（骨折和 迁移），这限制了现有PNS系统的使用。IPG进一步降低了这些风险， 足够薄以放置在残肢中，消除了导线穿过髋关节的需要， 避免了现有商业系统中经常引起故障的反复挠曲和弯曲。 拟议的CRP项目需要将该系统从早期阶段（第二阶段）推进到最后的后期阶段。 阶段（商业）设计，通过增强系统，使疼痛医生能够快速临床采用 植入工具（目标1），以减少复杂性和对支持人员的需求，同时利用熟悉的 这些医生中的绝大多数已经精通的程序方法。该项目也是 需要从早期阶段推进系统生产（计划在第二阶段项目中进行小批量生产， 每个IPG由熟练的技术人员在时间密集型过程中制造）到后期开发阶段 可持续、质量受控、大批量生产，符合良好生产规范（GMP）， 成功实现商业化。如果所有验证/确认测试均成功，则认为每个目标均成功 都通过了如果成功，最终产品将有可能满足截肢者及其家属的需求。 在FDA批准后，医生通过商业上可行和可持续的治疗。