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

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 pos...

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Main Authors: 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
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Language:English
Published: BMJ Publishing Group 2024-05-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/14/5/e083888.full
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author 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
author_facet 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
author_sort Jan D Reinhardt
collection DOAJ
description 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.
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spelling doaj-art-c703b690e9d047eba0afa631fd6e46c12025-08-20T02:40:33ZengBMJ Publishing GroupBMJ Open2044-60552024-05-0114510.1136/bmjopen-2024-083888Transcutaneous 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 ChinaJan D Reinhardt0Jin Liu1Ting Luo2Xiao Lu3Zhen-Yu Liu4Long-yun Zhou5Li-jun Peng6Ya-feng Liu7Shu-wei Wang8Yue Qiu9Si-jing Chen10Ming-ming Feng11Shan-shan Wu12Hui-juan Wu13Jiang-ping Ge148 Department of Health Sciences and Medicine, University of Lucerne, Lucerne, SwitzerlandDepartment of Neurology, Chongqing University Three Gorges Hospital, Chongqing, ChinaDepartment of Medical Oncology of Cancer Center, West China Hospital, Sichuan University, Chengdu, China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China3 Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People`s Republic of China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China1 Department of Rehabilitation Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People`s Republic of China2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China2 Department of Critical Care Medicine, Nanjing Zijin Hospital, Nanjing, People`s Republic of China3 Department of Critical Care Medicine, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, People`s Republic of China6 Nanjing Zijin Hospital, Nanjing, People`s Republic of ChinaIntroduction 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.https://bmjopen.bmj.com/content/14/5/e083888.full
spellingShingle 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
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
BMJ Open
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url https://bmjopen.bmj.com/content/14/5/e083888.full
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