NCT04050501

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
150

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Oct 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 5, 2019

Completed
3 days until next milestone

First Posted

Study publicly available on registry

August 8, 2019

Completed
2 months until next milestone

Study Start

First participant enrolled

October 9, 2019

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 16, 2023

Completed
1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

May 5, 2025

Completed
Last Updated

May 14, 2025

Status Verified

May 1, 2025

Enrollment Period

4.1 years

First QC Date

August 5, 2019

Last Update Submit

May 9, 2025

Conditions

Keywords

Brain infarctionBrain ischemiaVagus nerve stimulationPenumbra

Outcome Measures

Primary Outcomes (1)

  • Infarct volume

    Final infarct volume on MRI scan

    On day 5

Secondary Outcomes (11)

  • Feasibility of nVNS

    On day 5

  • Tolerability of nVNS

    On day 5

  • NIHSS (National Institutes of Health Stroke Scale) on day 5

    On day 5

  • Clinical outcome (modified Rankin Scale, mRS) on day 90

    On day 90

  • Occurrence of seizures in the first 90 days

    On day of admission, day 5 and day 90

  • +6 more secondary outcomes

Study Arms (2)

non-invasive Vagus Nerve Stimulation

ACTIVE COMPARATOR

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

Device: non-invasive Vagus Nerve Stimulator

Standard Care

NO INTERVENTION

Best medical practice alone

Interventions

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.

non-invasive Vagus Nerve Stimulation

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Leiden University Medical Center

Leiden, Netherlands

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Ischemic StrokeBrain InfarctionBrain Ischemia

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosis

Study Officials

  • Marieke JH Wermer, MD PhD

    Leiden University Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
PROBE design
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor Doctor

Study Record Dates

First Submitted

August 5, 2019

First Posted

August 8, 2019

Study Start

October 9, 2019

Primary Completion

November 16, 2023

Study Completion

May 5, 2025

Last Updated

May 14, 2025

Record last verified: 2025-05

Locations