Ischemic Stroke
Conditions
Keywords
Brain infarction, Brain ischemia, Vagus nerve stimulation, Penumbra
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.
Interventions
DEVICEnon-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.
Sponsors
Netherlands Organisation for Scientific Research
ElectroCore INC
Leiden University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
PROBE design
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Infarct volume | On day 5 | Final infarct volume on MRI scan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability of nVNS | On day 5 | Reached if less than 10% of the patients treated with nVNS has to abort treatment due to side effects |
| NIHSS (National Institutes of Health Stroke Scale) on day 5 | On day 5 | The scale runs from 0-42 and quantifies stroke severity |
| Clinical outcome (modified Rankin Scale, mRS) on day 90 | On day 90 | The scale runs from 0-6 and quantifies disabilities: 0 - No symptoms 1. \- No significant disability. Able to carry out all usual activities, despite some symptoms 2. \- Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities 3. \- Moderate disability. Requires some help, but able to walk unassisted 4. \- Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted 5. \- Severe disability. Requires constant nursing care and attention, bedridden, incontinent 6. \- Dead |
| Occurrence of seizures in the first 90 days | On day of admission, day 5 and day 90 | This will be asked to patients and their physician |
| Occurrence of headache in the first 90 days | On day of admission, day 5 and day 90 | A questionnaire will be taken adjusted from van Os et al., neurology 2016 |
| Feasibility of nVNS | On day 5 | Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge |
| Quality of life after 90 days | On day 90 | EQ5D-5L questionnaire will be taken. This questionnaire defines a health index based on different questions |
| Cognitive status on day 90 | On day 90 | TICS questionnaire will be taken. This questionnaire can assess cognitive status. |
| Penumbra recovery | On day 3 | Proportion of patients in whom \<50% of the penumbra turned into ischemic core on non-contrast CT |
| Blood-brain barrier measurement | On day 3 | Degree of blood-brain barrier leakage on day three measured with CTP |
| Occurrence of depression in the first 90 days | On day 90 | HADS (Hospital Anxiety and Depression Scale) questionnaire will be taken. The scale runs from 0-21 and defines the risk of having a depression |
Countries
Netherlands
Outcome results
None listed