SBIR-STTR Award

Direct to Phase II

It is estimated that 1 in 6 people worldwide will experience a stroke, with 50-70% experiencing chronicmovement impairment. While intensive motor training can partially restore motor function in theseindividuals, the improvement is often incomplete, as the physiological processes driving recovery throughmotor training alone are insufficient to fully restore function. Vagus Nerve Stimulation (VNS) paired withmotor training has recently emerged as a promising method to improve movement recovery by increasingneuroplasticity through targeted release of neurotransmitters. In a recent pilot study with individuals withchronic stroke, Kimberley et al. found large, clinically significant improvements in upper extremitymovement ability following an intervention of manually-triggered exercise-paired VNS compared tocontrol, also confirming that it was safe to deliver this stimulation at home. However, a manually triggeredVNS system has critical limitations. First, motor recovery is sensitive to stimulation timing but it isimpractical to optimize stimulation timing with a manually-triggered system in the clinic, and impossibleto do so at home. Second, operating a manually triggered system distracts therapists from optimallysupporting patients during therapy. An automated, closed-loop VNS delivery system could improve boththe practicality and therapeutic effects of exercise-paired VNS. Thus, for this Direct-to-Phase II SBIR, wepropose to complete development of a robust, FDA compliant, automatically triggered exercise-pairedVNS system called FitMi VNS system and to test the safety and usability of this system in the clinic and athome in an exploratory clinical trial with individuals with chronic stroke. Our specific aims for this PhaseII project are to: Aim 1) Complete an integrated FitMi VNS software system to mitigate potential risks anddevelop a HIPAA compliant remote monitoring platform; Aim 2) Complete bench-top verification andvalidation 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 eventsor safety-related issues; and Aim 3) Complete an at-home safety and feasibility study of FitMi VNS inindividuals 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 VNSin a large scale randomized controlled efficacy study in Phase III. At the end of this project, we will haverigorously refined the FitMi VNS system and performed initial safety and feasibility testing in the clinic andat 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.

Public Health Relevance Statement:
This research is relevant to public health because it will help support the development and commercialization of an automatically triggered exercise-paired VNS system, which will help facilitate delivery of plasticity enhancing exercise-paired VNS therapy through an engaging exercise platform both in the clinic and at home, thus improving the outcomes of rehabilitation therapy. This will provide a pathway to a better life for millions of U.S citizens suffering from motor impairment after stroke and other neurologic injuries. Not only does rehabilitation therapy reduce the likelihood of devastating complications, it also improves functional ability, increasing the standard of living of individuals with impairment and reducing the burden on society caused by disability.

Project Terms:
Activities of Daily Living ; Activities of everyday life ; daily living functionality ; functional ability ; functional capacity ; Automobile Driving ; driving ; Clinical Trials ; Exercise ; Feasibility Studies ; Feedback ; Goals ; Hand ; Manuals ; Methods ; Movement ; body movement ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Neuronal Plasticity ; CNS plasticity ; central nervous system plasticity ; neural plasticity ; neuroplastic ; neuroplasticity ; Patients ; Physiological Processes ; Organism-Level Process ; Organismal Process ; Physiologic Processes ; Pilot Projects ; pilot study ; Public Health ; Rehabilitation therapy ; Medical Rehabilitation ; Rehabilitation ; rehab therapy ; rehabilitative ; rehabilitative therapy ; Research ; Risk ; Rotation ; Safety ; Societies ; Computer software ; Software ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Supervision ; Testing ; Texas ; Translations ; Universities ; Vagus nerve structure ; Cranial Nerve X ; Pneumogastric Nerve ; Tenth Cranial Nerve ; Vagus Nerve ; Measures ; Living Standards ; Outcome Measure ; base ; sensor ; improved ; neurological rehabilitation ; Neuro rehabilitation ; Neurorehabilitation ; neurological rehab ; neurorehab ; stroke rehabilitation ; rehabilitation after stroke ; stroke rehab ; Chronic ; Phase ; Training ; disability ; Individual ; Recovery ; Funding ; Therapeutic ; Life ; Event ; Clinic ; Protocol ; Protocols documentation ; System ; experience ; Performance ; neurotransmitter release ; cohort ; HIPAA ; Kennedy Kassebaum Act ; PL 104-191 ; PL104-191 ; Public Law 104-191 ; United States Health Insurance Portability and Accountability Act ; Health Insurance Portability and Accountability Act ; novel ; Participant ; Devices ; Touch ; tactile sensation ; Touch sensation ; Nervous System Injuries ; Nervous System damage ; Neurological Damage ; Neurological Injury ; Neurological trauma ; neurotrauma ; Nervous System Trauma ; Adverse Experience ; Adverse event ; Intervention Strategies ; interventional strategy ; Intervention ; Membrum superius ; Upper Limb ; Upper Extremity ; Leg ; Data ; Motor ; randomisation ; randomization ; randomly assigned ; Randomized ; in vivo ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Wireless Technology ; wireless ; Therapeutic Effect ; Development ; developmental ; safety study ; Pathway interactions ; pathway ; post stroke ; after stroke ; poststroke ; software systems ; design ; designing ; vagus nerve stimulation ; Impairment ; clinically significant ; clinical significance ; Implant ; chronic stroke ; usability ; motor impairment ; movement impairment ; movement limitation ; functional restoration ; restore function ; restore functionality ; restore lost function ; commercialization ; primary outcome ; safety testing ; risk mitigation ; verification and validation ; arm ; motor recovery ; improved outcome ; safety and feasibility ; efficacy study ; recruit ; in vivo evaluation ; in vivo testing ; remote monitoring ; remote patient monitoring ; feasibility testing ; Home ;