The efficacy and safety of bilateral synchronous transcutaneous auricular vagus nerve stimulation for prolonged disorders of consciousness: a multicenter, double-blind, stratified, randomized controlled trial protocol

Abstract

Background: Treatment of disorders of consciousness (DOC) poses a huge challenge for clinical medicine. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation method, which shows potential in improving recovery of DOC. However, the evidence came from single-center, small-sample randomized controlled trial, which is insufficient to form a conclusion. Thereby, we propose a prospective, multicenter, double-blind, stratified, two-arm randomized controlled trial protocol to investigate the efficacy and safety of bilateral synchronous taVNS for treatment of DOC.

Methods: We aim to recruit 382 patients with prolonged DOC, and divide them into an active stimulation group and a sham stimulation group. The patients in the active stimulation group will receive bilateral synchronous taVNS with a 200 μs pulse width, 20 Hz frequency, and personal adjusted intensity. The sham stimulation group will wear the same stimulator but without current output. Both groups will receive treatment for 30 min per session, twice per day, 6 days per week lasting for 4 weeks. The clinical assessment including Coma Recovery Scale-Revised (CRS-R), Full Outline of Unresponsiveness (FOUR), Glasgow Coma Scale (GCS), and Extended Glasgow Outcome Scale (GOS-E) will be conducted to evaluate its efficacy. Heart rate variability (HRV), blood pressure, and adverse events will be recorded to evaluate its safety.

Discussion: These results will enable us to investigate the efficacy and safety of taVNS for DOC. This protocol will provide multicenter, large-sample, high-quality Class II evidence to support bilateral synchronous taVNS for DOC, and will advance the field of treatment options for DOC.Clinical trial registration:https://www.chictr.org.cn/showproj.html?proj=221851, ChiCTR2400081978.

Keywords: coma recovery scale-revised; disorders of consciousness; heart rate variability; randomized controlled trial; transcutaneous auricular vagus nerve stimulation.

Figure 1

Study flowchart. pDOC, prolonged disorders of consciousness.

Figure 2

(A) Bilateral synchronous taVNS device; (B) stimulation sites and electrodes.

Figure 3

Evaluation process. CRS-R, Coma Recovery Scale-Revised; FOUR, Full Outline of Unresponsiveness; GCS, Glasgow Coma Scale; GOS-E, Extended Glasgow Outcome Scale.