Transcutaneous auricular vagal nerve stimulation for consciousness recovery in patients with prolonged disorders of consciousness (TAVREC): study protocol for a multicenter, triple-blind, randomized controlled trial in China
Jan D Reinhardt,
Jin Liu,
Ting Luo,
Xiao Lu,
Zhen-Yu Liu,
Long-yun Zhou,
Li-jun Peng,
Ya-feng Liu,
Shu-wei Wang,
Yue Qiu,
Si-jing Chen,
Ming-ming Feng,
Shan-shan Wu,
Hui-juan Wu,
Jiang-ping Ge
Affiliations
Jan D Reinhardt
8 Department of Health Sciences and Medicine, University of Lucerne, Lucerne, Switzerland
Jin Liu
Department of Neurology, Chongqing University Three Gorges Hospital, Chongqing, China
Ting Luo
3 Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People`s Republic of China
Xiao Lu
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Zhen-Yu Liu
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Long-yun Zhou
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Li-jun Peng
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Ya-feng Liu
2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China
Shu-wei Wang
3 Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People`s Republic of China
Yue Qiu
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Si-jing Chen
1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China
Ming-ming Feng
2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China
Shan-shan Wu
2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China
Hui-juan Wu
3 Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People`s Republic of China
Jiang-ping Ge
6 Nanjing Zijin Hospital, Nanjing, People`s Republic of China
Introduction Prolonged disorders of consciousness (pDoC) are a catastrophic condition following brain injury with few therapeutic options. Transcutaneous auricular vagal nerve stimulation (taVNS), a safe, non-invasive intervention modulating thalamo-cortical connectivity and brain function, is a possible treatment option of pDoC. We developed a protocol for a randomised controlled study to evaluate the effectiveness of taVNS on consciousness recovery in patients with pDoC (TAVREC).Methods and analysis The TAVREC programme is a multicentre, triple-blind, randomised controlled trial with 4 weeks intervention followed by 4 weeks follow-up period. A minimum number of 116 eligible pDoC patients will be recruited and randomly receive either: (1) conventional therapy plus taVNS (30 s monophasic square current of pulse width 300 μs, frequency of 25 Hz and intensity of 1 mA followed by 30 s rest, 60 min, two times per day, for 4 weeks); or (2) conventional therapy plus taVNS placebo. Primary outcome of TAVREC is the rate of improved consciousness level based on the Coma Recovery Scale-Revised (CRS-R) at week 4. Secondary outcomes are CRS-R total and subscale scores, Glasgow Coma Scale score, Full Outline of UnResponsiveness score, ECG parameters, brainstem auditory evoked potential, upper somatosensory evoked potential, neuroimaging parameters from positron emission tomography/functional MRI, serum biomarkers associated with consciousness level and adverse events.Ethics and dissemination This study was reviewed and approved by the Research Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (Reference number: 2023-SR-392). Findings will be disseminated in a peer-reviewed journal and presented at relevant conferences.Trial registration number ChiCTR2300073950.