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

Not Applicable

Completed

• Conditions: Stroke, Ischemic; Stroke, Acute; Stroke; Stroke, Hemorrhagic
• Interventions: Device: Gammacore device; Device: Gammacore sham device

• Registration Number: NCT03733431
• Lead Sponsor: Turkish Stroke Research and Clinical Trials Network

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2018-11-03
• Study First Submitted QC: 2018-11-06
• Study First Posted: 2018-11-07
• Study Start: 2019-05-10
• Primary Completion: 2020-12-31
• Study Completion: 2021-04-01
• Status Verified: 2021-10
• Last Update Submitted: 2021-10-04
• Last Update Posted: 2021-10-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 69

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard dose vagal stimulation	Gammacore device	A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)
High dose vagal stimulation	Gammacore device	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)
Sham stimulation	Gammacore sham device	A total of 7 consecutive 2-minute trains at every 10 minutes for one hour (n=20)

Primary Outcome Measures

Name	Time	Method
Cardiovascular effects, clinical worsening or death (primary safety measure)	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

Trial Locations

Locations (8)

Ondokuz Mayıs University Faculty of Medicine; 🇹🇷 Samsun, Turkey

Hacettepe University Faculty of Medicine; 🇹🇷 Ankara, Turkey

Akdeniz University; 🇹🇷 Antalya, Turkey

Eskişehir Osmangazi Faculty of Medicine; 🇹🇷 Eskişehir, Turkey

Ankara University Faculty of Medicine; 🇹🇷 Ankara, Turkey

Gazi University Faculty Of Medicine; 🇹🇷 Ankara, Turkey

Necmettin Erbakan University; 🇹🇷 Konya, Turkey

Selcuk University; 🇹🇷 Konya, Turkey