Abstract WMP5: Non-invasive Vagus Nerve Stimulation For The Acute Treatment Of Ischemic Or Hemorrhagic Stroke

Background: This first-in-human randomized, blinded, sham-controlled, multicenter study assessed the safety and feasibility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of ischemic and hemorrhagic stroke. Potential efficacy was also assessed. Methods: Eligible participants admitted to nine clinical sites received standard care for acute stroke and were randomly assigned to low-dose nVNS, sham (2-minute stimulation applied to the skin overlying the vagus nerve every 10 minutes for an hour; 7 stimulations) or high-dose nVNS (2-minute stimulation every 10 minutes during hour 1 and hour 5; 14 stimulations) within 6 hours of stroke onset. Safety endpoints included severe bradycardia (≤50 beats/min) or significant hypotension (≥20-mm Hg reduction in arterial blood pressure) evaluated at 2 and 5 minutes after each stimulation and 30 minutes after the final stimulation. Feasibility was measured as the proportion of eligible patients in whom nVNS could be initiated within 6 hours of stroke onset and the ability to deliver scheduled stimulations per protocol. Efficacy measurements included absolute and relative infarct growth 24 hours poststroke compared to baseline and the proportion of patients with an NIH Stroke Scale (NIHSS) score of ≤4 or a ≥8-point improvement at 24 hours. Results: Sixty-eight patients with ischemic (n=60) or hemorrhagic (n=8) stroke completed the study. Baseline characteristics did not differ between sham (n=24) and nVNS (n=44). No significant bradycardia (2.9% of sham vs 3.1% of nVNS; p =0.965) or hypotension (1.1% of sham vs 2.5% of nVNS; p =0.145) occurred with nVNS. No deaths, acute coronary syndrome, symptomatic intracerebral hemorrhage, or stimulation site reactions were noted. All patients received 100% of intended stimulations per protocol. Clinical efficacy measures were similar between sham and total nVNS. Relative infarct growth, measured by diffusion weighted imaging, in the high dose nVNS group (63.3%) was lower than in the sham group (185.8%; p =0.05). Conclusions: This study suggests that nVNS is safe and feasible for the acute treatment for ischemic and hemorrhagic stroke. Possible efficacy is suggested by a decrease in relative infarct growth.