Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke

Not Applicable

Completed

• Conditions: Ischemic Stroke
• Interventions: Device: non-invasive Vagus Nerve Stimulator

• Registration Number: NCT04050501
• Lead Sponsor: Leiden University Medical Center

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-08-05
• Study First Submitted QC: 2019-08-07
• Study First Posted: 2019-08-08
• Study Start: 2019-10-09
• Primary Completion: 2023-11-16
• Status Verified: 2025-05
• Study Completion: 2025-05-05
• Last Update Submitted: 2025-05-09
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
non-invasive Vagus Nerve Stimulation	non-invasive Vagus Nerve Stimulator	non-invasive Vagus Nerve Stimulation on top of best medical practice

Primary Outcome Measures

Name	Time	Method
Infarct volume	On day 5	Final infarct volume on MRI scan

Secondary Outcome Measures

Name	Time	Method
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 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
Penumbra recovery	On day 3	Proportion of patients in whom \<50% of the penumbra turned into ischemic core on non-contrast CT
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
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
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
Blood-brain barrier measurement	On day 3	Degree of blood-brain barrier leakage on day three measured with CTP
Feasibility of nVNS	On day 5	Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge
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
NIHSS (National Institutes of Health Stroke Scale) on day 5	On day 5	The scale runs from 0-42 and quantifies stroke severity
Cognitive status on day 90	On day 90	TICS questionnaire will be taken. This questionnaire can assess cognitive status.

Trial Locations

Locations (1)

Leiden University Medical Center; 🇳🇱 Leiden, Netherlands