Clinical trial NCT03733431: Non-invasive TRanscutaneous Cervical Vagus Nerve Stimulation as a Treatment for Acute Stroke; Safety and Feasibility Study
Official title: Non-invasive TRanscutaneous Cervical Vagus Nerve Stimulation as a Treatment for Acute Stroke; Safety and Feasibility Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Stroke, Acute
Stroke, Ischemic
Stroke
Stroke, Hemorrhagic
Keywords: vagal nerve stimulation
Lead sponsor: Turkish Stroke Research and Clinical Trials Network
Sponsor class: NETWORK
Collaborators: name: Turkish Neurological Society
name: ElectroCore INC
First posted: 2018-11-07
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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.

Primary outcomes:
measure: Cardiovascular effects, clinical worsening or death (primary safety measure)
timeFrame: 24 hours
Secondary outcomes:
Other outcomes:
measure: Proportion of treatment eligible patients (feasibility measure 1)
timeFrame: 6 hours
measure: Proportion of patients completing all pre-specified treatment doses (feasibility measure 2)
timeFrame: 12 hours
measure: Stroke onset to treatment time (feasibility measure 3)
timeFrame: 6 hours
measure: Early neurological outcome (efficacy measure 1)
timeFrame: 24 hours
measure: Early tissue outcome (efficacy measure 2)
timeFrame: 24 hours
measure: Local reaction at application site (secondary safety measure 1)
timeFrame: 12 hours
measure: Acute coronary syndrome (secondary safety measure 2)
timeFrame: 24 hours
measure: Symptomatic intracerebral hemorrhage (secondary safety measure 3)
timeFrame: 24 hours
measure: Death, clinical worsening, and acute coronary syndrome (secondary safety measure 4)
timeFrame: 24 hours
measure: New ischemic lesion or increase in hemorrhage (secondary safety measure 5)
timeFrame: 24 hours
measure: Serious adverse device event (SADE) rate (secondary safety measure 6)
timeFrame: 24 hours
Locations:
city: Ankara
country: Turkey
facility: Ankara University Faculty of Medicine
city: Ankara
country: Turkey
facility: Gazi University Faculty Of Medicine
city: Ankara
country: Turkey
facility: Hacettepe University Faculty of Medicine
city: Antalya
country: Turkey
facility: Akdeniz University
city: Eskişehir
country: Turkey
facility: Eskişehir Osmangazi Faculty of Medicine
city: Konya
country: Turkey
facility: Necmettin Erbakan University
city: Konya
country: Turkey
facility: Selcuk University
city: Samsun
country: Turkey
facility: Ondokuz Mayıs University Faculty of Medicine
Study officials:
affiliation: Hacettepe University
name: Ethem M Arsava, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hacettepe University
name: Mehmet A Topcuoglu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Massachusetts General Hospital, Harvard University
name: Hakan Ay, MD
role: STUDY_CHAIR
References:
citation: 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.