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

NCT ID: NCT03733431

Last Updated: 2021-10-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-10
• Study Completion Date: 2021-04-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: SINGLE

Study Groups

Standard dose vagal stimulation

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

Group Type: ACTIVE_COMPARATOR

Gammacore device

Intervention Type: 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

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)

Group Type: ACTIVE_COMPARATOR

Gammacore device

Intervention Type: 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 stimulation

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

Group Type: SHAM_COMPARATOR

Gammacore sham device

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Turkish Neurological Society

UNKNOWN

Sponsor Role: collaborator

ElectroCore INC

INDUSTRY

Sponsor Role: collaborator

Turkish Stroke Research and Clinical Trials Network

NETWORK

Sponsor Role: lead

Responsible Party

Ethem Murat Arsava

Professor of Neurology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ethem M Arsava, MD

Role: PRINCIPAL_INVESTIGATOR

Hacettepe University

Mehmet A Topcuoglu, MD

Role: PRINCIPAL_INVESTIGATOR

Hacettepe University

Hakan Ay, MD

Role: STUDY_CHAIR

Massachusetts General Hospital, Harvard University

Locations

Ankara University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Gazi University Faculty Of Medicine

Ankara, , Turkey (Türkiye)

Hacettepe University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Akdeniz University

Antalya, , Turkey (Türkiye)

Eskişehir Osmangazi Faculty of Medicine

Eskişehir, , Turkey (Türkiye)

Necmettin Erbakan University

Konya, , Turkey (Türkiye)

Selcuk University

Konya, , Turkey (Türkiye)

Ondokuz Mayıs University Faculty of Medicine

Samsun, , Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 36356829 (View on PubMed)

Other Identifiers

TR-VENUS

Identifier Type: -

Identifier Source: org_study_id