Single-centre, randomised and double-blind clinical trial on the efficacy of transcutaneous auricular vagus nerve stimulation in preventing and treating primary headache in children and adolescents: a study protocol.

INTRODUCTION: Primary headaches pose a significant burden on children and adolescents, highlighting the need for effective non-pharmacological interventions. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive modality that has demonstrated efficacy in adult populations with primary headaches and has shown safety in adolescents with mental health disorders. However, its effectiveness in managing acute headache episodes and preventing recurrences in paediatric populations remains underexplored. This study aims to evaluate the immediate analgesic effects of taVNS during acute headache episodes and its preventive efficacy over a 4-week period. Additionally, we will investigate potential biomarkers associated with primary headaches and elucidate the underlying mechanisms of taVNS through electromyography (EMG) and electrocardiography (ECG) assessments. METHODS AND ANALYSIS: This study will employ a double-blind, randomised clinical trial design involving 288 children and adolescent participants diagnosed with primary headaches. The study will consist of two substudies: the acute period (AP) study and the preventive period (PP) study. Participants will be randomly allocated to receive either taVNS or sham stimulation. The primary outcome for the AP study will be the reduction of pain intensity 2 hours after treatment, as measured by the visual analogue scale, while the PP study will assess the change in the headache attack days over the treatment period. Secondary outcomes will include EMG and ECG parameters. ETHICS AND DISSEMINATION: The study will adhere to the principles outlined in the Declaration of Helsinki and has received ethical approval from the Medical Ethics Committee of Nanfang Hospital, Southern Medical University (NFEC-2024-057), on 2 January 2024. Informed consent will be obtained from all participants or their guardians. The findings will be disseminated through peer-reviewed journals and presented at relevant scientific conferences. TRIAL REGISTRATION NUMBER: NCT06277063.