Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke

Ischemic Stroke Clinical Trial

— NOVIS  

Official title:

Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04050501
• Other study ID #: NL64702.058.18
• Status: Recruiting
• Phase: N/A
• Start date: October 9, 2019
• Est. completion date: March 2024

Study information

• Verified date: March 2023
• Source: Leiden University Medical Center
• Contact: Anne van der Meij, PhD
• Phone: 0031715261899
• Email: novis[@]lumc.nl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 150
• Est. completion date: March 2024
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

Device:
• 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.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (3)

Lead Sponsor	Collaborator
Leiden University Medical Center	ElectroCore INC, Netherlands Organisation for Scientific Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Infarct volume	Final infarct volume on MRI scan	On day 5
Secondary	Feasibility of nVNS	Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge	On day 5
Secondary	Tolerability of nVNS	Reached if less than 10% of the patients treated with nVNS has to abort treatment due to side effects	On day 5
Secondary	NIHSS (National Institutes of Health Stroke Scale) on day 5	The scale runs from 0-42 and quantifies stroke severity	On day 5
Secondary	Clinical outcome (modified Rankin Scale, mRS) on day 90	The scale runs from 0-6 and quantifies disabilities: 0 - No symptoms; - No significant disability. Able to carry out all usual activities, despite some symptoms; - Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities; - Moderate disability. Requires some help, but able to walk unassisted; - Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted; - Severe disability. Requires constant nursing care and attention, bedridden, incontinent; - Dead	On day 90
Secondary	Occurrence of seizures in the first 90 days	This will be asked to patients and their physician	On day of admission, day 5 and day 90
Secondary	Occurrence of headache in the first 90 days	A questionnaire will be taken adjusted from van Os et al., neurology 2016	On day of admission, day 5 and day 90
Secondary	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	On day 90
Secondary	Quality of life after 90 days	EQ5D-5L questionnaire will be taken. This questionnaire defines a health index based on different questions	On day 90
Secondary	Cognitive status on day 90	TICS questionnaire will be taken. This questionnaire can assess cognitive status.	On day 90
Secondary	Penumbra recovery	Proportion of patients in whom <50% of the penumbra turned into ischemic core on non-contrast CT	On day 3
Secondary	Blood-brain barrier measurement	Degree of blood-brain barrier leakage on day three measured with CTP	On day 3