Clinical trial NCT04050501: Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke
Official title: Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ischemic Stroke
Keywords: Brain infarction
Brain ischemia
Vagus nerve stimulation
Penumbra
Lead sponsor: Leiden University Medical Center
Sponsor class: OTHER
Collaborators: name: Netherlands Organisation for Scientific Research
name: ElectroCore INC
First posted: 2019-08-08
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Infarct volume
timeFrame: On day 5
Secondary outcomes:
measure: Feasibility of nVNS
timeFrame: On day 5
measure: Tolerability of nVNS
timeFrame: On day 5
measure: NIHSS (National Institutes of Health Stroke Scale) on day 5
timeFrame: On day 5
measure: Clinical outcome (modified Rankin Scale, mRS) on day 90
timeFrame: On day 90
measure: Occurrence of seizures in the first 90 days
timeFrame: On day of admission, day 5 and day 90
measure: Occurrence of headache in the first 90 days
timeFrame: On day of admission, day 5 and day 90
measure: Occurrence of depression in the first 90 days
timeFrame: On day 90
measure: Quality of life after 90 days
timeFrame: On day 90
measure: Cognitive status on day 90
timeFrame: On day 90
measure: Penumbra recovery
timeFrame: On day 3
measure: Blood-brain barrier measurement
timeFrame: On day 3
Other outcomes:
Locations:
city: Leiden
country: Netherlands
facility: Leiden University Medical Center
Study officials:
affiliation: Leiden University Medical Center
name: Marieke JH Wermer, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.