Stroke is highly prevalent, debilitating, and lacks consistently effective post-injury interventions. We have developed an innovative technique using vagus nerve stimulation (VNS) delivered during rehabilitation to engage plasticity-enhancing neuromodulatory circuits and improve recovery of motor and sensory function after stroke. Our preclinical findings demonstrate that VNS paired with rehabilitative training enhances recovery in multiple models of neurological injury, including ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and spinal cord injury. Moreover, our two recent clinical studies in chronic stroke patients indicate that VNS is safe and yields a significant three-fold increase in recovery of upper limb function compared to rehabilitation without VNS. While the scientific and clinical evidence is encouraging, the VNS device used to perform these studies is substantially limited by an inflexible stimulation paradigm, lead fragility, limited battery life, large size, and high cost. These technical limitations preclude effective translation of this potentially transformative therapy. We have developed a novel low-cost, clinical-grade VNS system that obviates these deficiencies. The system consists of a miniature wireless, lead-less, passive implantable stimulator that is placed on the vagus nerve and an external power and communications module that controls the implantable stimulator. The implantable device is manufactured at the wafer level using an automated process with materials that are FDA-approved for human use and MRI-compatible, thus providing reliability and lowering cost 25-fold compared to commercially-available devices. The implantable stimulator is hermetically encapsulated in biocompatible glass and is 50 times smaller than existing VNS devices, reducing the invasiveness of the implant surgery. Moreover, the implanted device is passive and harvests power from the external module, eliminating the need for a bulky implanted battery and surgical revision for battery replacement. Much of the required testing is complete, but final verification and validation is necessary to allow IDE submission and clinical evaluation. In this proposal, we outline a series of critical steps to translate this robust, cost-effective device to provide tangible improvements in the lives of stroke patients. In the UG3 phase, we will finalize verification and validation of the embedded software and create a design history file. Additionally, we will confirm biocompatibility in a chronic large animal study and finalize package sterility testing. Once complete, we will gain approval for an IDE. In the UH3 phase, we will perform a double-blind, randomized, placebo-controlled crossover study to evaluate the VNS therapy system in chronic stroke patients. Successful completion of this project will move this device from the verge of translation into human trials with a direct focus on a subsequent pivotal trial.
Vagus nerve stimulation (VNS) has the potential to transform rehabilitation for stroke, but successful translation of this therapy is limited by the cost, size, power consumption, lead fragility, and technical features of commercially available VNS devices. We have developed a novel wireless, lead-less, low-cost clinical grade device to obviate these challenges. Here, we propose to finalize testing to meet FDA regulatory standards and perform a first-in-human clinical study that will lead directly to a pivotal clinical study.
