Preparing for a clinical trial to implement a fully implanted neuroprosthesis to restore walking after partial paralysis

The long-term objective of this project is to improve the walking speed and stability of Veterans disabled by incomplete SCI (iSCI), stroke, or multiple sclerosis sufficiently to safely participate in community activities outside of the home, and thereby enhance their independence and daily function. We will advance this goal by

implementing the Networked Neuroprosthesis System (NNPS), a fully implanted neuroprosthesis that stimulates peripheral nerves to augment the actions of selected weak or paralyzed muscles based on real-time feedback of voluntary body movements. The system is currently under evaluation for hand function in people

with SCI; this overall project would extend the technology to new applications and user-populations. This Stage 1 proposal will ready the team for a Stage 2 submission. Specifically, we will achieve the following aims: 1) Verify the pre-clinical test plan for the NNPS. We anticipate that we already completed most of the pre-

clinical testing as part of a separate prior IDE submission to evaluate the NNPS for hand function after SCI. We will confirm the following additional tests: 1) MRI compatibility modeling and testing to identify whether NNPS users are allowed to undergo MRI testing. This test will enable people with MS to

receive the implanted system while continuing routine MRI testing. 2) battery drainage testing to verify the remaining time that the system can run to requiring recharge, so that an alert can be incorporated into the user interface to provide warnings about time remaining. 3) Additional electrical safety tests that

are now required since the prior IDE was submitted. Any additional tests that the FDA identifies will be added to the Stage 2 pre-clinical test as well. During Stage 1 we will also identify contractors for any tests that need to be conducted offsite (e.g. MRI compatibility testing). 2) Confirm the clinical test plan to evaluate the NNPS in people with partial paralysis for walking. We

propose a case series where each person serves as their own longitudinal and concurrent control. The primary comparison will be walking capability after receiving the implant comparing the device turned on relative to walking with the device turned off. Each implant recipient will receive a system customized to their unique needs. The system will be tuned and then users will be trained to walk with

the system at home and in the community to facilitate independent use. During pre-submission meetings with the FDA we will confirm the inclusion/exclusion criteria, outcome measures, and risk analysis to maximize participant safety and potential benefit. 3) Prepare for Stage 2 submission and execution. Based on feedback from the FDA, we will revise our

pre-clinical and clinical testing plans for the Stage 2 submission. At the same time we will identify any necessary contractors for tests that must be completed externally or begin developing the test plans for internal tests. We will also determine necessary elements for the clinical test plan and any remaining

human factors and usability testing required prior to IDE submission. This Stage 1 project is a critical step in moving towards restoring independence for Veterans with paralysis. It will prepare for a VA Translational Rehabilitation Research Award: Stage 2 and then a subsequent pivotal trial by determining what the FDA will require and creating the plans for to complete those tests and begin an early

feasibility study. The results will identify potential impact sizes for powering a clinical trial and identify methods to refine related to implantation, system tuning, and user training. Successful completion of this project will define a new intervention for Veterans with difficulty walking due to partial paralysis such as stroke, MS, and

iSCI, thus enabling them to be independent ambulators and accelerating their access to life opportunities as active participants in their communities and society at large.