Pan Yuanhang, Zhang Yingchi, Xu Ziliang, Wei Zihan, Pan Rui, Hu Gengyao, Wang Xiaoli, Yang Lei, Wu Dianwei, Zhang Xinbo, Wen Xinyu, Qu Shuyi, Li Chenwei, Zhu Zhe, Gao Yuwen, Shi Xiaodan, Zhu Yuanqiang, Wu Kejian, Wang Duolao, Liu Yonghong
Department of Neurology, Xijing Hospital, Air Force Medical University, Xi'an, PR China.
Department of Radiology, Xijing Hospital, Air Force Medical University, Xi'an, PR China.
Neurotherapeutics. 2025 Jul;22(4):e00604. doi: 10.1016/j.neurot.2025.e00604. Epub 2025 May 6.
To assess exploratorily the safety and efficacy of transcutaneous auricular vagus nerve stimulation (tVNS) as an adjunctive therapy in improving symptoms in patients with narcolepsy type 1 (NT1). The TARGET-NT1 trial, a two-arm, double-blinded, sham-controlled trial was conducted from April 2022, to June 2024 at Xijing Hospital in Xi'an, China. Participants were randomised to receive tVNS treatment or sham tVNS (stVNS) treatment. Both interventions were performed for two 30-min periods per day with the same stimulation parameters but different stimulation points, for 12 weeks. The primary outcome was the change in mean sleep onset latency of maintenance of wakefulness test (MWT) from baseline to week 12. Secondary outcomes included changes in Narcolepsy Severity Scale (NSS), Epworth Sleepiness Scale (ESS), 14-item Hamilton Anxiety Rating Scale (HAMA-14), 17-item Hamilton Depression Rating Scale (HAMD-17). Among 60 randomised participants (32 men [53.3 %] and 28 [46.7 %]; mean [SD] age, 29.9 [9.9] years), 56 were included in the modified intention-to-treat (mITT) analysis. From baseline to week 12, the difference in mean change in mean sleep onset latency of MWT was 3.09 (95 % CI, 1.00, 5.88; P = 0.0041) as compared with stVNS group. Significant improvements in NSS-EDS (-2.61 [95%CI, -4.07, -1.15; P = 0.0006]), NSS-SP (-1.11 [95%CI, -1.83, -0.38; P = 0.0030]), NSS-HH (-2.71 [95%CI, -3.36, -2.05; P < 0.0001]), NSS- DNS (-0.52 [95%CI, -0.87, -0.17; P = 0.0036]), ESS (-3.03 [95%CI, -4.30, -1.75; P < 0.0001]) and HAMD-17 (-2.50 [95%CI, -4.30, -0.70; P = 0.0069]) were observed in the tVNS group as compared with stVNS group. This exploratory study supported the efficacy and safety of tVNS in patients with NT1 and provided insights into the mechanisms underlying tVNS treatment for NT1. The findings highlight tVNS as a potential non-pharmacological adjunctive therapy for patients with NT1. This trial was registered with the Chinese Clinical Trial Registry, ChiCTR2400094550.
探索性评估经皮耳迷走神经刺激（tVNS）作为辅助治疗改善1型发作性睡病（NT1）患者症状的安全性和有效性。TARGET-NT1试验是一项双臂、双盲、假对照试验，于2022年4月至2024年6月在中国西安的西京医院进行。参与者被随机分配接受tVNS治疗或假tVNS（stVNS）治疗。两种干预措施均每天进行两个30分钟疗程，刺激参数相同但刺激点不同，持续12周。主要结局是从基线到第12周，清醒维持试验（MWT）的平均睡眠开始潜伏期的变化。次要结局包括发作性睡病严重程度量表（NSS）、爱泼华嗜睡量表（ESS）、14项汉密尔顿焦虑量表（HAMA-14）、17项汉密尔顿抑郁量表（HAMD-17）的变化。在60名随机参与者中（32名男性[53.3%]和28名[46.7%]；平均[标准差]年龄为29.9[9.9]岁），56名被纳入改良意向性分析（mITT）。与stVNS组相比，从基线到第12周，MWT的平均睡眠开始潜伏期的平均变化差异为3.09（95%CI，1.00，5.88；P = 0.0041）。与stVNS组相比，tVNS组在NSS-EDS（-2.61[95%CI，-4.07，-1.15；P = 0.0006]）、NSS-SP（-1.11[95%CI，-1.83，-0.38；P = 0.0030]）、NSS-HH（-2.71[95%CI，-3.36，-2.05；P < 0.0001]）、NSS-DNS（-0.52[95%CI，-0.87，-0.17；P = 0.0036]）、ESS（-3.03[95%CI，-4.30，-1.75；P < 0.0001]）和HAMD-17（-2.50[95%CI，-4.30，-0.70；P = 0.0069]）方面有显著改善。这项探索性研究支持了tVNS对NT1患者的疗效和安全性，并为tVNS治疗NT1的潜在机制提供了见解。研究结果突出了tVNS作为NT1患者潜在的非药物辅助治疗方法。该试验已在中国临床试验注册中心注册，注册号为ChiCTR2400094550。
