Safety and efficacy of transcutaneous auricular vagus nerve stimulation in patients with narcolepsy type 1 (TARGET-2): study protocol for a randomised, double-blind, sham-controlled trial
Yuanhang Pan, Yingchi Zhang, Gengyao Hu, Xiaoli Wang, Lei Yang, Na Yuan, Yuanyuan Jia, Fengli Hao, Jing Kang, Haoyu Ye, Xinyu Wen, Chenwei Li, Zhe Zhu, Dianwei Wu, Kejian Wu, Yonghong LiuIntroduction
Narcolepsy type 1 (NT1) is a chronic neurological disorder characterised by excessive daytime sleepiness, cataplexy and disturbed nocturnal sleep. Current pharmacological treatments often have limited efficacy, significant side effects or potential for abuse. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that has shown promise in regulating sleep–wake cycles and neural network activity. Preliminary evidence from our prior study on Transcutaneous Auricular Vagus Nerve Stimulation in patients with NT1 (TARGET-NT1 study) suggests potential benefits of taVNS for NT1. The TARGET-2 trial aims to evaluate the efficacy and safety of bilateral taVNS compared with unilateral taVNS and sham stimulation in patients with NT1.
Methods and analysis
TARGET-2 is a randomised double-blind trial. A total of 153 participants with NT1 will be recruited from four centres in China. Participants will be randomly allocated (1:1:1) to receive either (1) bilateral taVNS (active stimulation on both ears), (2) unilateral taVNS (active stimulation on the left ear only) or (3) sham taVNS (minimal intensity stimulation on both ears). Participants and outcome assessors are blinded. The intervention will be administered twice daily for 30 min per session over 12 weeks. The primary outcome is the change in the Epworth Sleepiness Scale (ESS) score from baseline to the 12-week endpoint. Secondary outcomes are changes in the narcolepsy severity scale score, Pittsburgh Sleep Quality Index, fatigue severity scale score, 14-item Hamilton Anxiety Rating Scale score and 17-item Hamilton Depression Rating Scale score, as well as responder rates (proportion with ≥25% ESS reduction) from baseline to week 12. Safety will be assessed by monitoring adverse events.
Ethics and dissemination
Ethical approval has been granted by the Medical Ethical Committee of Xijing Hospital (Approval Number: XJLL-KY-20252403). Written informed consent will be obtained from all participants before initiating any study-specific procedures. The results will be submitted for publication in a peer-reviewed journal. The anticipated completion date for reporting of the study results is 31 March 2027.
Trial registration
Chinese Clinical Trial Registry, ChiCTR2500110531 (registered on 15 October 2025).