Implantable Peripheral Nerve Stimulator for Treatment of Phantom Limb Pain

摘要 据报道，多达80%的截肢者会患上慢性幻肢疼痛(PLP)。描述了PLP 感觉失去的肢体部分有灼热、扭曲、发痒或受压的感觉。这些痛苦的感觉有一种实质性的 对生活质量的负面影响；患有PLP的人抑郁、睡眠困难、经常缺勤的比例很高 远离工作，与家人/朋友分离，限制使用假肢。使用药物来缓解PLP是 在控制疼痛方面只有50%左右有效；此外，这些药物有许多令人不快的副作用。阿片类药物 是一种常用的药物治疗方法，通常与其他药物联合使用。非制药类 据报道，PLP的管理方法只有30%的成功率。植入式脊椎疼痛刺激器有 在治疗PLP方面仅显示了有限的有效性；在靶向受影响的神经组织方面缺乏特异性 降低了临床益处。相比之下，已有研究表明，刺激用于恢复失踪者的感觉 利福平对PLP有很好的清除作用。恢复这些缺失的感觉输入改变了外周的中央处理 感觉，从而减轻截肢的疼痛。此外，感觉恢复也有改善的好处 假体的稳定性和具体化。 为了回应对PLP改进治疗的需要，Ripple建议开发一种可植入的神经刺激 系统为假肢使用者提供自然、直观的感觉。在印刷方面经验丰富，自定义，灵活， 高度耐用的植入式电极阵列。我们相信我们的神经袖带技术符合 能够提供一致和可控的电刺激的感觉反馈系统。加上Ripple的 多通道植入式刺激器，我们相信这种定制的电极阵列将比现有的 治疗PLP的选择。我们已经开发出了这种植入式多通道刺激器，具有任意传送的能力 多个独立通道上的波形刺激脉冲，这是感觉反馈所需的功能 刺激。作为DARPA HAPTIX项目的系统集成商，我们已经开发了一个可植入的原型 能够通过刺激周围神经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身体研究评估的阵列架构，将电极与我们的 植入式刺激器，在加速寿命内进行电气和机械性能的台式验证 测试，将植入物送出进行第三方系统生物兼容性评估，并完成为期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提交一个IDE，以进行首次人体测试 植入式系统。 在第二阶段，我们会进行一项由5名受试者组成的临床研究，以测试植入式刺激系统。 科罗拉多州丹佛市的长老会圣卢克医疗中心。詹卡洛·巴罗拉特博士是神经刺激疗法的世界专家。 大卫·哈恩博士是肢体保存研究所的负责人，这是一家专门研究 截肢和复杂的肢体手术。每个单侧假体使用者将被植入一年，因为我们评估了 这种植入性装置治疗PLP的安全性和有效性。

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.