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

NCT03733431 | Completed DMC FDA Device

• 1 other identifier: TR-VENUS
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

Stroke, Acute; Stroke, Ischemic; Stroke; Stroke, Hemorrhagic

Keywords

vagal nerve stimulation

Outcome Measures

Primary Outcomes (1)

• Cardiovascular effects, clinical worsening or death (primary safety measure)

  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 Outcomes (11)

• Proportion of treatment eligible patients (feasibility measure 1)

  6 hours

• Proportion of patients completing all pre-specified treatment doses (feasibility measure 2)

  12 hours

• Stroke onset to treatment time (feasibility measure 3)

  6 hours

Study Arms (3)

Standard dose vagal stimulation

ACTIVE COMPARATOR

A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)

Device: Gammacore device

High dose vagal stimulation

ACTIVE COMPARATOR

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

Sham stimulation

SHAM COMPARATOR

A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)

Device: Gammacore sham device

Interventions

Gammacore device DEVICE

Transcutaneous stimulation of vagus nerve with the device positioned below the mandibular angle, medial to the sternocleidomastoid muscle and lateral to the larynx.

High dose vagal stimulation; Standard dose vagal stimulation

Gammacore sham device 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.

Sham stimulation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Turkish Stroke Research and Clinical Trials Network: lead
• Turkish Neurological Society: collaborator
• ElectroCore INC: collaborator

Study Sites (8)

Ankara University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

Gazi University Faculty Of Medicine

Ankara, Turkey (Türkiye)

Location

Hacettepe University Faculty of Medicine

Ankara, Turkey (Türkiye)

Location

Akdeniz University

Antalya, Turkey (Türkiye)

Location

Eskişehir Osmangazi Faculty of Medicine

Eskişehir, Turkey (Türkiye)

Location

Necmettin Erbakan University

Konya, Turkey (Türkiye)

Location

Selcuk University

Konya, Turkey (Türkiye)

Location

Ondokuz Mayıs University Faculty of Medicine

Samsun, Turkey (Türkiye)

Location

Related Publications (1)

• Arsava EM, Topcuoglu MA, Ay I, Ozdemir AO, Gungor IL, Togay Isikay C, Nazliel B, Kozak HH, Ozturk S, Yilmaz IA, Dora B, Ay H; TR-VENUS investigators. Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke. Brain Stimul. 2022 Nov-Dec;15(6):1467-1474. doi: 10.1016/j.brs.2022.10.012. Epub 2022 Nov 7.

  PMID: 36356829 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke; Hemorrhagic Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Ethem M Arsava, MD

  Hacettepe University

  PRINCIPAL INVESTIGATOR

• Mehmet A Topcuoglu, MD

  Hacettepe University

  PRINCIPAL INVESTIGATOR

• Hakan Ay, MD

  Massachusetts General Hospital, Harvard University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: November 3, 2018
• First Posted: November 7, 2018
• Study Start: May 10, 2019
• Primary Completion: December 31, 2020
• Study Completion: April 1, 2021
• Last Updated: October 5, 2021

Record last verified: 2021-10

Locations

TU (8)