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 >99% 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.
