Brain Stimulation (Nov 2022)
Assessment of safety and feasibility of non-invasive vagus nerve stimulation for treatment of acute stroke
- Ethem Murat Arsava,
- Mehmet Akif Topcuoglu,
- Ilknur Ay,
- Atilla Ozcan Ozdemir,
- Ibrahim Levent Gungor,
- Canan Togay Isikay,
- Bijen Nazliel,
- Hasan Huseyin Kozak,
- Serefnur Ozturk,
- İbrahim Arda Yilmaz,
- Babur Dora,
- Hakan Ay,
- Ali Unal,
- Tugba Ozel,
- Mine Hayriye Sorgun,
- Eda Aslanbaba Bahadır,
- Elif Peker,
- Ozlem Aykac,
- Zaur Mehdiyev,
- Hale Zeynep Batur Caglayan,
- Asli Akyol Gurses,
- Mehmet Yasir Pektezel,
- Ezgi Yilmaz,
- Dogan Dinc Oge,
- Safak Parlak,
- Ahmet Bugrul,
- Hilal Ozguner,
- Aysu Cetiner Seker,
- Gokhan Ozdemir,
- Gozde Ongun,
- Sueda Ecem Yilmaz,
- Cihat Ozguncu,
- Saziye Melike Turan Isik,
- Omer Faruk Ildiz,
- Azer Mammadli,
- Aydin Talip Yildogan,
- Candace McClure
Affiliations
- Ethem Murat Arsava
- Department of Neurology, Hacettepe University, Ankara, Turkey; Corresponding author. Department of Neurology, Faculty of Medicine, Hacettepe University, 06230 Altindag, Ankara, Turkey.
- Mehmet Akif Topcuoglu
- Department of Neurology, Hacettepe University, Ankara, Turkey
- Ilknur Ay
- Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Atilla Ozcan Ozdemir
- Department of Neurology, Eskishehir Osmangazi University, Eskisehir, Turkey
- Ibrahim Levent Gungor
- Department of Neurology, Ondokuz Mayis University, Samsun, Turkey
- Canan Togay Isikay
- Department of Neurology, Ankara University, Ankara, Turkey
- Bijen Nazliel
- Department of Neurology, Gazi University, Ankara, Turkey
- Hasan Huseyin Kozak
- Department of Neurology, Necmettin Erbakan University, Konya, Turkey
- Serefnur Ozturk
- Department of Neurology, Selcuk University, Konya, Turkey
- İbrahim Arda Yilmaz
- Department of Neurology, Mersin University, Mersin, Turkey
- Babur Dora
- Department of Neurology, Akdeniz University, Antalya, Turkey
- Hakan Ay
- Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
- Ali Unal
- Department of Neurology, Akdeniz University, Antalya, Turkey
- Tugba Ozel
- Department of Neurology, Akdeniz University, Antalya, Turkey
- Mine Hayriye Sorgun
- Department of Neurology, Ankara University, Ankara, Turkey
- Eda Aslanbaba Bahadır
- Department of Neurology, Ankara University, Ankara, Turkey
- Elif Peker
- Department of Radiology, Ankara University, Ankara, Turkey
- Ozlem Aykac
- Department of Neurology, Eskishehir Osmangazi University, Eskisehir, Turkey
- Zaur Mehdiyev
- Department of Neurology, Eskishehir Osmangazi University, Eskisehir, Turkey
- Hale Zeynep Batur Caglayan
- Department of Neurology, Gazi University, Ankara, Turkey
- Asli Akyol Gurses
- Department of Neurology, Gazi University, Ankara, Turkey
- Mehmet Yasir Pektezel
- Department of Neurology, Hacettepe University, Ankara, Turkey
- Ezgi Yilmaz
- Department of Neurology, Hacettepe University, Ankara, Turkey
- Dogan Dinc Oge
- Department of Neurology, Hacettepe University, Ankara, Turkey
- Safak Parlak
- Department of Radiology, Hacettepe University, Ankara, Turkey
- Ahmet Bugrul
- Department of Neurology, Necmettin Erbakan University, Konya, Turkey
- Hilal Ozguner
- Department of Neurology, Mersin University, Mersin, Turkey
- Aysu Cetiner Seker
- Department of Neurology, Ondokuz Mayis University, Samsun, Turkey
- Gokhan Ozdemir
- Department of Neurology, Selcuk University, Konya, Turkey
- Gozde Ongun
- Department of Neurology, Selcuk University, Konya, Turkey
- Sueda Ecem Yilmaz
- Department of Neurology, Selcuk University, Konya, Turkey
- Cihat Ozguncu
- Department of Neurology, Selcuk University, Konya, Turkey
- Saziye Melike Turan Isik
- Department of Neurology, Selcuk University, Konya, Turkey
- Omer Faruk Ildiz
- Department of Neurology, Selcuk University, Konya, Turkey
- Azer Mammadli
- Department of Neurology, Selcuk University, Konya, Turkey
- Aydin Talip Yildogan
- Department of Neurology, Selcuk University, Konya, Turkey
- Candace McClure
- North American Science Associates Inc., Minneapolis, MN, USA
- Journal volume & issue
-
Vol. 15,
no. 6
pp. 1467 – 1474
Abstract
Background: Non-invasive vagus nerve stimulation (nVNS) using a hand-held stimulator placed on the neck is an FDA-approved treatment for primary headache disorders. The safety of nVNS is unknown in stroke patients. Objective: To assess the safety and feasibility of nVNS for the acute treatment of stroke. Methods: TR-VENUS (clinicaltrials.gov identifier NCT03733431) was a randomized, sham-controlled, open-label, multicenter trial conducted in patients with acute ischemic stroke (IS) or intracerebral hemorrhage (ICH). Patients were randomly assigned to standard-dose nVNS, high-dose nVNS, or sham stimulation. The primary endpoint was a composite safety outcome defined as bradycardia or reduction in mean arterial blood pressure during treatment or progression of neurological or death within 24 h of treatment. The feasibility endpoints were the proportion of eligible subjects receiving nVNS within 6 h of symptom onset and the proportion completing all pre-specified treatment doses. Efficacy assessments included infarct growth from baseline to 24 h after treatment. Results: Sixty-nine patients (61 IS, 8 ICH) completed the study. The composite safety outcome was achieved in 32.0% in sham and 47.7% in nVNS group (p = 0.203). Treatment was initiated in all but two randomized patients. All dosed subjects received 100% of prespecified stimulations. A non-significant reduction in infarct growth was observed in the high-dose nVNS group (184.2% in sham vs. 63.3% in high-dose nVNS; p = 0.109). Conclusions: The results of this study suggest that nVNS may be safe and feasible in the setting of acute stroke. These findings support further development of nVNS as a potential treatment for acute ischemic stroke.
