Ischemic StrokeNOVISNCT04050501
Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke
A study testing non-invasive Vagus Nerve Stimulator in people with Ischemic Stroke, run by Leiden University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ischemic Stroke
- What is being tested?
- non-invasive Vagus Nerve Stimulator
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteNetherlands
- Study dates
- 9 Oct 2019to 5 May 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
- Conditions
- Ischemic Stroke
- Being tested
- non-invasive Vagus Nerve Stimulator
- Keywords
- Brain infarction, Brain ischemia, Vagus nerve stimulation, Penumbra
- Medical subject headings
- Ischemic Stroke, Brain Infarction, Brain Ischemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
non-invasive Vagus Nerve StimulatorDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| non-invasive Vagus Nerve Stimulation | Active comparator | non-invasive Vagus Nerve Stimulation on top of best medical practice Receives: Device: non-invasive Vagus Nerve Stimulator |
| Standard Care | No intervention | Best medical practice alone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Infarct volume
Final infarct volume on MRI scan
Measured: On day 5
Secondary outcomes (11)
Feasibility of nVNS
Reached if more than 75% of the nVNS treated patients complete treatment for five days or until discharge
Measured: 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
Measured: On day 5
NIHSS (National Institutes of Health Stroke Scale) on day 5
The scale runs from 0-42 and quantifies stroke severity
Measured: On day 5
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
Measured: On day 90
Occurrence of seizures in the first 90 days
This will be asked to patients and their physician
Measured: 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
Measured: 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
Measured: 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
Measured: On day 90
Cognitive status on day 90
TICS questionnaire will be taken. This questionnaire can assess cognitive status.
Measured: On day 90
Penumbra recovery
Proportion of patients in whom <50% of the penumbra turned into ischemic core on non-contrast CT
Measured: On day 3
Blood-brain barrier measurement
Degree of blood-brain barrier leakage on day three measured with CTP
Measured: On day 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2019
- Study start9 Oct 2019
- Primary completion16 Nov 2023
- Study completion5 May 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ischemic StrokeStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 150 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research, ElectroCore INC
- Responsible party
- Principal investigator, Marieke JH Wermer, MD, Leiden University Medical Center
- Investigators
- Marieke JH Wermer, MD PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04050501
- Sponsor's protocol ID
- NL64702.058.18
- Acronym
- NOVIS
- Status last verified
- May 2025
- First submitted
- 5 Aug 2019
- Last updated
- 14 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Publications
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.
PubMed 33106174
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Vagus Nerve Stimulation in Acute Ischemic Stroke
- ClinicalTrials.gov ID
- NCT04050501
- Acronym / sponsor ID
- NOVIS / NL64702.058.18
- Conditions
- Ischemic Stroke
- Keywords
- Brain infarction, Brain ischemia, Vagus nerve stimulation, Penumbra
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 150 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Netherlands Organisation for Scientific Research, ElectroCore INC
- Study start
- 9 Oct 2019 (actual)
- Primary completion
- 16 Nov 2023 (actual)
- Study completion
- 5 May 2025 (actual)
- First posted
- 8 Aug 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| non-invasive Vagus Nerve Stimulation | Active comparator | Device: non-invasive Vagus Nerve Stimulatornon-invasive Vagus Nerve Stimulation on top of best medical practice |
| Standard Care | No intervention | –Best medical practice alone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (10 listed)
- A life expectancy of less than three months
- mRS >2 prior to admission
- Contra-indication for contrast CT
- Contra-indications for VNS:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| non-invasive Vagus Nerve StimulatorTwo 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. | Device | non-invasive Vagus Nerve Stimulation |
Primary outcome
Infarct volume
Time frame: On day 5
Final infarct volume on MRI scan
11 secondary outcomes
Feasibility of nVNS
Time frame: On day 5
Tolerability of nVNS
Time frame: On day 5
NIHSS (National Institutes of Health Stroke Scale) on day 5
Time frame: On day 5
Clinical outcome (modified Rankin Scale, mRS) on day 90
Time frame: On day 90
Occurrence of seizures in the first 90 days
Time frame: On day of admission, day 5 and day 90
Occurrence of headache in the first 90 days
Time frame: On day of admission, day 5 and day 90
Occurrence of depression in the first 90 days
Time frame: On day 90
Quality of life after 90 days
Time frame: On day 90
Cognitive status on day 90
Time frame: On day 90
Penumbra recovery
Time frame: On day 3
Blood-brain barrier measurement
Time frame: On day 3
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2025.
- Derived from this study: PubMed 33106174van 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marieke JH Wermer, MD PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing non-invasive Vagus Nerve Stimulator in people with Ischemic Stroke, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Infarct volume (time frame: On day 5). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04050501, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2025.