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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
150
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.
Leiden University Medical Center
Leiden, Netherlands
Infarct volume
Final infarct volume on MRI scan
Time frame: On day 5
Feasibility of nVNS
Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge
Time frame: On day 5
Tolerability of nVNS
Reached if less than 10% of the patients treated with nVNS has to abort treatment due to side effects
Time frame: On day 5
NIHSS (National Institutes of Health Stroke Scale) on day 5
The scale runs from 0-42 and quantifies stroke severity
Time frame: On day 5
Clinical outcome (modified Rankin Scale, mRS) 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
Time frame: On day 90
Occurrence of seizures in the first 90 days
This will be asked to patients and their physician
Time frame: On day of admission, day 5 and day 90
Occurrence of headache in the first 90 days
A questionnaire will be taken adjusted from van Os et al., neurology 2016
Time frame: On day of admission, day 5 and day 90
Occurrence of depression in the first 90 days
HADS (Hospital Anxiety and Depression Scale) questionnaire will be taken. The scale runs from 0-21 and defines the risk of having a depression
Time frame: On day 90
Quality of life after 90 days
EQ5D-5L questionnaire will be taken. This questionnaire defines a health index based on different questions
Time frame: On day 90
Cognitive status on day 90
TICS questionnaire will be taken. This questionnaire can assess cognitive status.
Time frame: On day 90
Penumbra recovery
Proportion of patients in whom \<50% of the penumbra turned into ischemic core on non-contrast CT
Time frame: On day 3
Blood-brain barrier measurement
Degree of blood-brain barrier leakage on day three measured with CTP
Time frame: On day 3
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.