title: Transcutaneous auricular vagus nerve stimulation for pediatric epilepsy: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Recently, clinical observations reported the potential benefit of vagus nerve stimulation (VNS) for pediatric epilepsy. Transcutaneous auricular vagus nerve stimulation (ta-VNS) is a newer non-invasive VNS, making it more accessible for treating pediatric epilepsy, yet there is limited clinical evidence for its effectiveness.
  
  
  METHODS
  A three-center, randomized, parallel, controlled trial will be carried out to evaluate whether ta-VNS improves pediatric epilepsy. Pediatric patients aged 2 to 14 years with epilepsy will be recruited and randomly assigned to transcutaneous auricular vagus nerve stimulation (ta-VNS) group, transcutaneous auricular non-vagus nerve stimulation (tan-VNS) group, and control group with a 1:1: sqrt(2) allocation, as per a computer generated randomization schedule stratified by study center using permuted blocks of random sizes. We will use Zelen's design, in which randomization occurs before informed consent. Patients in the stimulation groups will receive tan-VNS or ta-VNS three times a day for 6 months. Patients in the control group will not be provided with any stimulation during the 6 months. The guardians of the patients are required to keep a detailed diary to record the data. Outcome assessment including seizure frequency, electroencephalogram (EEG), heart rate variability (HRV) analysis, quality of life (QOL) and adverse events will be made at baseline and 2, 4 and 6 months after ta-VNS initiation. The seizure frequency and adverse events will be followed up at 1 year and 1.5 years after ta-VNS initiation.
  
  
  CONCLUSIONS
  Results of this trial will help clarify whether ta-VNS treatment is beneficial for pediatric patients, and will make clear whether the anticonvulsive effect of ta-VNS is correlated with the improvement of sympathovagal imbalance.
  
  
  BACKGROUND
  
  
  
  BACKGROUND
  NCT02004340 . Registration date: 13 November 2013.
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hazel7811@hotmail.com.|Hubei University of Chinese Medicine/Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, 430061, China. hazel7811@hotmail.com.
authors: Wei
authors: W
authors: He
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. xiaorain_wang@hotmail.com.
authors: Xiao-Yu
authors: XY
authors: Wang
authors: Beijing Tian Tan Hospital, Capital Medical University, Beijing, 100050, China. zl_wh_china@163.com.
authors: Li
authors: L
authors: Zhou
authors: Beijing Tian Tan Hospital, Capital Medical University, Beijing, 100050, China. Lizm1211@163.com.
authors: Zhi-Mei
authors: ZM
authors: Li
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. xianghongjing@hotmail.com.
authors: Xiang-Hong
authors: XH
authors: Jing
authors: Beijing Children Hospital, Capital Medical University, Beijing, 100045, China. zhongli_lu@hotmail.com.
authors: Zhong-Li
authors: ZL
authors: Lv
authors: Clinical Evaluation Center, Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China. snowmanzhao@163.com.
authors: Yu-Feng
authors: YF
authors: Zhao
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. sh700330@hotmail.com.
authors: Hong
authors: H
authors: Shi
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. hulinlin1980@126.com.
authors: Ling
authors: L
authors: Hu
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. suyangshuai@163.com.
authors: Yang-Shuai
authors: YS
authors: Su
authors: Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing, 100700, China. zhubing@mail.cintcm.ac.cn.|Hubei University of Chinese Medicine/Innovation Center of Preventive Treatment by Acupuncture and Moxibustion, Wuhan, 430061, China. zhubing@mail.cintcm.ac.cn.
authors: Bing
authors: B
authors: Zhu
mesh_terms: D000293:Adolescent; D000367:Age Factors; D001921:Brain / Q000503:physiopathology*; D058256:Brain Waves; D002648:Child; D002675:Child, Preschool; D002681:China; D002985:Clinical Protocols; D004423:Ear / Q000294:innervation*; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000503:physiopathology / Q000628:therapy*; D005260:Female; D006339:Heart Rate; D006801:Humans; D008297:Male; D011788:Quality of Life; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D055536:Vagus Nerve Stimulation / Q000009:adverse effects / Q000379:methods*