Implantable Peripheral Nerve Stimulator for Treatment of Phantom Limb Pain

植入式周围神经刺激器治疗幻肢痛

• 批准号: 9932778
• 负责人: Andrew Wilder
• 金额: $ 198.34万
• 依托单位: RIPPLE, LLC
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9932778
• 关键词: Amputation; Animals; Architecture; Cadaver; Caliber; Chronic; Clinical; Clinical Research; Complex; Coupled; Custom; Data; Development; Dissociation; Effectiveness; Electric Stimulation; Electrodes; Esthesia; Evaluation; Family; Feeling; Fiber; Friends; Implant; Institution; Intuition; Limb structure; Massage; Mechanics; Medical Device Designs; Medical center; Mental Depression; Nerve; Nerve Block; Operative Surgical Procedures; Opioid; Pain; Pain management; Performance; Peripheral; Peripheral Nerve Stimulation; Peripheral Nerves; Phantom Limb Pain; Pharmaceutical Preparations; Pharmacological Treatment; Phase; Physiologic pulse; Polymers; Presbyterian Church; Printing; Prosthesis; Pruritus; Quality of life; Reporting; Safety; Sensory; Site; Sleep; Specificity; Spine pain; System; Technology; Telemetry; Testing; Tissues; Training; Work; base; biomaterial compatibility; chronic pain; desensitization; design; effective therapy; experience; falls; first-in-human; flexibility; implantable device; improved; limb amputation; neural stimulation; neurotransmission; non-opioid analgesic; novel; pain sensation; preservation; pressure; prosthesis wearer; prototype; relating to nervous system; response; restoration; sensory feedback; sensory input; side effect; signal processing; success

Abstract Chronic phantom limb pain (PLP) has been reported to inflict as many as 80% of people with amputations. PLP is described as feeling like burning, twisting, itching, or pressure in part of the missing limb. These painful sensations have a substantial negative impact on quality of life; people who suffer PLP have high rates of depression, difficulty sleeping, regular absences from work, dissociation with family/friends, and limited use of their prostheses. The use of medications to alleviate PLP is only about 50% effective at managing pain; additionally, these medications have many undesirable side effects. Opioids are a commonly prescribed pharmacological treatment, typically in conjuection with other medications. Non-pharmaceutical approaches to PLP management have been reported with only 30% success rates. Implantable spinal pain stimulators have demonstrated only limited effectiveness in managing PLP; the lack of specificity in targeting effected neural tissue diminishes clinical benefit. In contrast, it has been demonstrated that stimulation used to restore sensation from the missing limb is highly effective at eliminating PLP. Restoring these missing sensory inputs alters central processing of peripheral sensation, thereby mitigating pain from the amputated limb. In addition, sensory restoration has the benefit of improving stability and embodiment of a prosthesis. In response to the need for improved treatment for PLP, Ripple proposes to develop an implantable neural stimulation system to provide natural and intuitive sensation for prosthesis users. Ripple is experienced in printing custom, flexible, and highly durable implantable electrode arrays. We are confident our nerve cuff technology meets all the requirements for a sensory feedback system capable of providing consistent and controlled electrical stimulation. Coupled with Ripple’s multichannel implantable stimulator, we believe this custom electrode array will offer substantial improvement over existing options to treat PLP. We have developed this implantable multichannel stimulator with the capabilites of delivering arbitrary waveform stimulation pulses on multiple independent channels, which are features required for sensory feedback stimulation. As a system integrator on the DARPA HAPTIX project, we have already developed a prototype implantable stimulator capable of restoring sensation from a missing limb via peripheral nerve stimulation. In Phase I, we will finalize array architectures for evaluation in cadaver studies, complete integration of electrodes with our implantable stimulator, conduct benchtop verification of electrical and mechanical performance in accelerated lifetime testing, send implants out for third-party evaluation of system biocompatibility, and complete a 6-month GLP animal study to validate safety and efficacy. At the end of Phase I, we will submit an IDE to the FDA for first-in-human testing of the implantable system. In Phase II, we will conduct a 5-subject clinical study to test the implantable stimulation system with the clinical team at Presbyterian St. Luke’s Medical Center in Denver, CO. Dr. Giancarlo Barolat is a world expert in neurostimulation therapy for chronic pain and Dr. David Hahn leads the Institution for Limb Preservation, an advanced center specializing in amputations and complex limb surgeries. Each unilateral prosthesis user will be implanted for one year as we evaluate the safety and efficacy of this implantable device to treat PLP.

摘要 据报道，慢性幻肢痛（PLP）造成多达80%的截肢者。PLP描述 感觉像燃烧，扭曲，发痒，或在失踪的肢体部分的压力。这些痛苦的感觉有一个实质性的 对生活质量的负面影响;患有PLP的人有很高的抑郁率，睡眠困难，经常缺席 工作、与家人/朋友分离以及假肢使用有限。使用药物缓解PLP是 只有约50%的有效控制疼痛;此外，这些药物有许多不希望的副作用。阿片 是一种常用的药物治疗，通常与其他药物结合使用。非药物 据报道，PLP管理方法的成功率仅为30%。植入式脊柱疼痛刺激器具有 在治疗PLP方面仅表现出有限的有效性;在靶向影响神经组织方面缺乏特异性 减少了临床益处。相反，已经证明，用于从缺失中恢复感觉的刺激 肢体在消除PLP方面非常有效。恢复这些缺失的感觉输入会改变外周神经元的中枢处理。 感觉，从而减轻截肢的疼痛。此外，感觉恢复的好处是改善 假体稳定性和实施例。 为了满足改善PLP治疗的需要，涟漪提出开发一种植入式神经刺激器， 系统为假肢使用者提供自然和直观的感觉。涟漪在印刷定制方面经验丰富，灵活， 高度耐用的可植入电极阵列。我们有信心我们的神经袖带技术满足所有要求， 能够提供一致和受控的电刺激的感觉反馈系统。再加上涟漪的 多通道植入式刺激器，我们相信这种定制的电极阵列将提供比现有的 选择治疗PLP。我们已经开发出这种植入式多通道刺激器， 在多个独立通道上波形刺激脉冲，这是感觉反馈所需的特征 刺激.作为DARPA HAPTIX项目的系统集成商，我们已经开发出一种原型植入式 能够通过外周神经刺激恢复缺失肢体感觉的刺激器。 在第一阶段，我们将最终确定用于尸体研究评估的阵列架构，完成电极与我们的 植入式刺激器，在加速寿命期内进行电气和机械性能实验室验证 测试，将植入物送出进行系统生物相容性的第三方评价，并完成6个月的GLP动物研究 以验证安全性和有效性。在第一阶段结束时，我们将向FDA提交一份IDE，用于首次人体试验。 可植入系统。 在第二阶段，我们将进行一项5名受试者的临床研究，与临床团队在 长老会圣卢克医疗中心在丹佛，CO博士吉安卡洛巴罗拉特是一个世界神经刺激治疗专家 大卫哈恩博士领导的肢体保护机构，一个先进的中心，专门研究 截肢和复杂的肢体手术。每名单侧假体使用者将植入一年， 该植入式器械治疗PLP的安全性和有效性。