Non-invasive TRanscutaneous Cervical Vagus Nerve Stimulation as a Treatment for Acute Stroke; Safety and Feasibility Study (TR-VENUS)

October 4, 2021 updated by: Ethem Murat Arsava, Turkish Stroke Research and Clinical Trials Network
This study aims to determine safety and feasibility of non-invasive transcutaneous cervical Vagus nerve stimulation (nVNS) when delivered promptly after clinical diagnosis of acute stroke. Vagus nerve stimulation will be performed via GammaCore® device. A total of 60 patients will be randomized to each of 3 different groups; 'standard dose' vagal stimulation, 'high dose' vagal stimulation, and 'sham stimulation' (1:1:1 ratio). Adverse device events, serious adverse device events, and feasibility of vagal nerve stimulation at the setting of acute stroke will be evaluated. The study will be performed in a multi-center fashion among stroke centers within TurkStrokeNet Network.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey
      • Ankara, Turkey
        • Ankara University Faculty of Medicine
      • Ankara, Turkey
        • Gazi University Faculty of Medicine
      • Ankara, Turkey
        • Hacettepe University Faculty of Medicine
      • Antalya, Turkey
        • Akdeniz University
      • Eskişehir, Turkey
        • Eskişehir Osmangazi Faculty of Medicine
      • Konya, Turkey
        • Necmettin Erbakan Üniversity
      • Konya, Turkey
        • Selcuk University
      • Samsun, Turkey
        • Ondokuz Mayıs University Faculty of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male or female patients who are older than 18 years old who have been admitted to neurological intensive care or stroke units with ischemic or hemorrhagic stroke
  • Patients with symptom onset time within 6 hours or with unknown time of onset and no evidence of acute ischemia on fluid attenuation inversion recovery (FLAIR) imaging
  • Patients who have given written informed consent prior to undertaking any study-related procedure.

Exclusion Criteria:

  • Patients who have a pre-stroke disability ≥ 2 according to the modified Rankin Score
  • Patients who have a NIH Stroke Scale/Score (NIHSS) ≤ 4 or ≥30
  • Patients who have a NIHSS item 1a ≥2
  • Patients who have experienced early dramatic neurological improvement (NIHSS score improvement ≥8) prior to study randomization suggesting resolution of signs/symptoms of stroke
  • Patients with classical lacunar syndrome
  • Patients who have local infection, rash or space occupying lesion at the stimulation site
  • Patients with a prior injury to the vagus nerve (cervical vagotomy)
  • Patients with conditions that make the positioning of the device not possible such as tonic head deviation or involuntary movements of the head and neck
  • Patients using medications that can interfere with central neurotransmitter mechanisms potentially involved in the central vagal pathway (complete list is provided below under concomitant medications)
  • Patients with known severe (>90% stenosis) bilateral carotid artery disease
  • Patients with known carotid hypersensitivity
  • Patients who had undergone bilateral carotid endarterectomy or neck surgery involving the region of carotid triangle
  • Patients who have low blood pressure (Baseline SBP≤100 mmHg or DBP≤60 mmHg)
  • Patients who have slow heart rate (Baseline HR≤60/min)
  • Patients who have high blood pressure (SBP>220 mmHg or DBP>130 mmHg) despite initial line of treatment
  • Patients who have been involved in any investigational study within the previous 90 days
  • Patients who have any terminal illness such that the patient would not be expected to survive more than 90 days
  • Pregnant women
  • Patients with severe hypoglycemia at admission (<60 mg/dl)
  • Patient experiencing seizures
  • Patients with baseline ECG showing first-degree AV block; second- or third-degree atrio-ventricular block with no pacemaker/ICD in place; or ventricular tachycardia/fibrillation
  • Patients with digitalis toxicity
  • Patients who are suspected to have an acute coronary syndrome after clinical evaluations (Clinical, ECG, or any related biomarker)
  • Patients who are scheduled to have an emergent carotid artery angioplasty stenting or endarterectomy
  • Patients implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant.
  • Patients implanted with metal cervical spine hardware or having a metallic implant near the GammaCore stimulation site.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Active Comparator: Standard dose vagal stimulation
A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)
Device: Gammacore device
Transcutaneous stimulation of vagus nerve with the device positioned below the mandibular angle, medial to the sternocleidomastoid muscle and lateral to the larynx.
Active Comparator: High dose vagal stimulation
A total of 7 consecutive 2-minute trains applied at every 10 minutes for one hour that is followed by an additional 7 consecutive 2-minute trains interspersed at every 10 minutes applied 3 hours after completion of the initial scheme (n=20)
Device: Gammacore device
Transcutaneous stimulation of vagus nerve with the device positioned below the mandibular angle, medial to the sternocleidomastoid muscle and lateral to the larynx.
Sham Comparator: Sham stimulation
A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)
Device: Gammacore sham device
Sham device which does not deliver electrical stimulation, but instead, produces a buzzing sound will be placed along the lateral border of the sternocleidomastoid muscle in order to avoid mechanical stimulation of the vagus nerve in the carotid triangle.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Cardiovascular effects, clinical worsening or death (primary safety measure)
Time Frame: 24 hours

any of the following:

  • severe bradycardia (HR ≤50/min) during treatment application
  • significant decrease in arterial blood pressure (≥20 mmHg decrease in mean arterial blood pressure) during treatment application
  • neurological worsening (progression of neurologic deficit as shown by ≥ 4 points increase in NIH Stroke Scale Score) within 24 hours
  • death within 24 hours
24 hours

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Proportion of treatment eligible patients (feasibility measure 1)
Time Frame: 6 hours
Proportion of eligible patients in whom nVNS can be started within the first 6 hours.
6 hours
Proportion of patients completing all pre-specified treatment doses (feasibility measure 2)
Time Frame: 12 hours
Proportion of enrolled patients who receive all the pre-specified treatment doses per protocol.
12 hours
Stroke onset to treatment time (feasibility measure 3)
Time Frame: 6 hours
Time from stroke onset to administration of the first dose of nVNS.
6 hours
Early neurological outcome (efficacy measure 1)
Time Frame: 24 hours
Proportion of patients with NIHSS score≤4 or improvement of baseline NIHSS score ≥8 at 24 hours
24 hours
Early tissue outcome (efficacy measure 2)
Time Frame: 24 hours
Delta infarct volume between baseline DWI and 24 hr MRI.
24 hours
Local reaction at application site (secondary safety measure 1)
Time Frame: 12 hours
Local irritation or skin reaction during treatment application
12 hours
Acute coronary syndrome (secondary safety measure 2)
Time Frame: 24 hours
Acute coronary syndrome
24 hours
Symptomatic intracerebral hemorrhage (secondary safety measure 3)
Time Frame: 24 hours
Symptomatic intracerebral hemorrhage: ≥ 4 points increase in NIH Stroke Scale Score (NIHSS) together with a PH2 (parenchymal hematoma-2) type intracerebral hemorrhage
24 hours
Death, clinical worsening, and acute coronary syndrome (secondary safety measure 4)
Time Frame: 24 hours
Combined outcome of death, clinical worsening, and acute coronary syndrome
24 hours
New ischemic lesion or increase in hemorrhage (secondary safety measure 5)
Time Frame: 24 hours
New, spatially distinct remote ischemic lesion outside the arterial territory of the index lesion on MRI at 24 hours or greater than 30% increase in hemorrhage volume from baseline CT to 24 hour MRI in the subset with intracerebral hemorrhage
24 hours
Serious adverse device event (SADE) rate (secondary safety measure 6)
Time Frame: 24 hours
Serious adverse device event (SADE) rate at 24 hours
24 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Turkish Stroke Research and Clinical Trials Network

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
ElectroCore INC
Turkish Neurological Society

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ethem M Arsava, MD, Hacettepe University
  • Principal Investigator: Mehmet A Topcuoglu, MD, Hacettepe University
  • Study Chair: Hakan Ay, MD, Massachusetts General Hospital, Harvard University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 10, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 3, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 6, 2018

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 7, 2018

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 5, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • TR-VENUS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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