Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke

NCT ID: NCT04050501

Last Updated: 2025-05-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-09
• Study Completion Date: 2025-05-05

Brief Summary

The main objective of the study will be to investigate whether treatment with non-invasive vagus nerve stimulation (nVNS) on top of best medical practice in acute ischemic stroke patients results in less infarct growth in the penumbra and smaller infarct volumes compared with those of patients not treated with nVNS. The study will be a prospective randomized clinical trial with blinded outcome assessment (PROBE design). 150 patients will be randomized to nVNS with the gammaCore Sapphire™ device on top of best medical practice versus best medical practice alone (including intravenous thrombolysis and/or thrombectomy if indicated). If patients are randomized to nVNS, two stimulations of two minutes each will be applied in the neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be applied every 8 hours over the next 5 days or until discharge, whichever occurs first. The stimulation side in the neck will be the radiological side of the stroke. The primary endpoint will be the final infarct volume on MRI scan on day 5 of patients treated with nVNS compared with those of patients not treated with VNS.

Conditions

Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

non-invasive Vagus Nerve Stimulation

non-invasive Vagus Nerve Stimulation on top of best medical practice

Group Type: ACTIVE_COMPARATOR

non-invasive Vagus Nerve Stimulator

Intervention Type: DEVICE

Two stimulations of two minutes each will be applied in the neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be applied every 8 hours over the next 5 days or until discharge, whichever occurs first. The stimulation side in the neck will be the radiological side of the stroke.

Standard Care

Best medical practice alone

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

non-invasive Vagus Nerve Stimulator

Two stimulations of two minutes each will be applied in the neck every 15 minutes in the first 3 hours. Thereafter two stimulations will be applied every 8 hours over the next 5 days or until discharge, whichever occurs first. The stimulation side in the neck will be the radiological side of the stroke.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Ischemic stroke
• NIHSS ≥1
• Perfusion deficit on the admission CTP scan; the penumbra must comprise at least 1/3 of the total ischemic area (ischemic core and penumbra)
• The infarct has to comprise the anterior circulation
• Treatment has to start <12 hours after stroke onset
• Patients or their representatives need to give their informed consent

Exclusion Criteria

• A life expectancy of less than three months
• mRS >2 prior to admission
• Contra-indication for contrast CT
• Contra-indications for VNS:

• An active implantable medical device such as a pacemaker, deep brain stimulator, or any implanted electronic device
• Symptomatic stenosis or dissection of the carotid artery (in these patients the other side will be stimulated unless a significant stenosis on the other side is present as well)
• Structural abnormality e.g. lymphadenopathy, previous surgery or abnormal anatomy (in these patients the other side will be stimulated)
• Metal cervical spine hardware or metallic implant near the stimulation site
• Cervical vagotomy (in these patients the other side will be stimulated)
• Pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Netherlands Organisation for Scientific Research

OTHER_GOV

Sponsor Role: collaborator

ElectroCore INC

INDUSTRY

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Marieke JH Wermer, MD

Professor Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marieke JH Wermer, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

References

van der Meij A, van Walderveen MAA, Kruyt ND, van Zwet EW, Liebler EJ, Ferrari MD, Wermer MJH. NOn-invasive Vagus nerve stimulation in acute Ischemic Stroke (NOVIS): a study protocol for a randomized clinical trial. Trials. 2020 Oct 26;21(1):878. doi: 10.1186/s13063-020-04794-1.

Reference Type: DERIVED

PMID: 33106174 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

NL64702.058.18

Identifier Type: -

Identifier Source: org_study_id