Implantable Peripheral Nerve Stimulator for Treatment of Phantom Limb Pain

摘要

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.