NOn-invasive Vagus nerve stimulation in acute Ischemic Stroke (NOVIS): a study protocol for a randomized clinical trial

Anne van der Meij, Marianne A A van Walderveen, Nyika D Kruyt, Erik W van Zwet, Eric J Liebler, Michel D Ferrari, Marieke J H Wermer, Anne van der Meij, Marianne A A van Walderveen, Nyika D Kruyt, Erik W van Zwet, Eric J Liebler, Michel D Ferrari, Marieke J H Wermer

Abstract

Background: Secondary damage due to neurochemical and inflammatory changes in the penumbra in the first days after ischemic stroke contributes substantially to poor clinical outcome. In animal models, vagus nerve stimulation (VNS) inhibits these detrimental changes and thereby reduces tissue injury. The aim of this study is to investigate whether non-invasive cervical VNS (nVNS) in addition to the current standard treatment can improve penumbral recovery and limit final infarct volume.

Methods: NOVIS is a single-center prospective randomized clinical trial with blinded outcome assessment. One hundred fifty patients will be randomly allocated (1:1) within 12 h from clinical stroke onset to nVNS for 5 days in addition to standard treatment versus standard treatment alone. The primary endpoint is the final infarct volume on day 5 assessed with MRI.

Discussion: We hypothesize that nVNS will result in smaller final infarct volumes as compared to standard treatment due to improved penumbral recovery. The results of this study will be used to assess the viability and approach to power a larger trial to more definitively assess the clinical efficacy of nVNS after stroke.

Trial registration: ClinicalTrials.gov NCT04050501 . Registered on 8 August 2019.

Keywords: Acute ischemic stroke; Penumbra; Randomized controlled trial; Secondary damage; Spreading depolarizations; Vagus nerve stimulation.

Conflict of interest statement

EL is a full-time employee of electroCore Inc. and receives stock options. MF reports grants and consultancy or industry support from electroCore, Medtronic, Eli Lilly, Amgen, Novartis, and TEVA, and independent support from The Netherlands Organization for Scientific Research (NWO), The Netherlands Organization for Health Research and Development (ZonMW), The Dutch Brain and Heart Foundations, The Dutch Ministry of Health, and The NutsOhra Foundation from the Dutch Insurance Companies. The other authors declare that they have no competing interests.

Figures

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Trial logo

References

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