FitMi VNS: The First Automated Home Therapy System for Exercise-Paired Vagus Nerve Stimulation After Stroke

It is estimated that 1 in 6 people worldwide will experience a stroke, with 50-70% experiencing chronic movement impairment. While intensive motor training can partially restore motor function in these individuals, the improvement is often incomplete, as the physiological processes driving recovery through motor training alone are insufficient to fully restore function. Vagus Nerve Stimulation (VNS) paired with motor training has recently emerged as a promising method to improve movement recovery by increasing neuroplasticity through targeted release of neurotransmitters. In a recent pilot study with individuals with chronic stroke, Kimberley et al. found large, clinically significant improvements in upper extremity movement ability following an intervention of manually-triggered exercise-paired VNS compared to control, also confirming that it was safe to deliver this stimulation at home. However, a manually triggered VNS system has critical limitations. First, motor recovery is sensitive to stimulation timing but it is impractical to optimize stimulation timing with a manually-triggered system in the clinic, and impossible to do so at home. Second, operating a manually triggered system distracts therapists from optimally supporting patients during therapy. An automated, closed-loop VNS delivery system could improve both the practicality and therapeutic effects of exercise-paired VNS. Thus, for this Direct-to-Phase II SBIR, we propose to complete development of a robust, FDA compliant, automatically triggered exercise-paired VNS system called FitMi VNS system and to test the safety and usability of this system in the clinic and at home in an exploratory clinical trial with individuals with chronic stroke. Our specific aims for this Phase II project are to: Aim 1) Complete an integrated FitMi VNS software system to mitigate potential risks and develop a HIPAA compliant remote monitoring platform; Aim 2) Complete bench-top verification and validation testing and supervised, in-vivo safety testing of FitMi VNS in individuals with chronic stroke (n = 10). Here, our goal is for rt99% of stimulations to be delivered with optimal timing and no adverse events or safety-related issues; and Aim 3) Complete an at-home safety and feasibility study of FitMi VNS in individuals with chronic stroke (n = 20). Our hypothesis is that FitMi VNS will safely provide closed-loop, exercise-paired VNS both in the clinic and at home. We will evaluate the therapeutic benefit of FitiMi VNS in a large scale randomized controlled efficacy study in Phase III. At the end of this project, we will have rigorously refined the FitMi VNS system and performed initial safety and feasibility testing in the clinic and at home. If successful, FitMi VNS will be the first system to provide automated, closed-loop exercise- paired VNS for stroke rehabilitation, leading to a step change in motor recovery for individuals with stroke.