nVNS for the Prevention and Treatment of Primary Headache

NCT06277063 | Recruiting

• 1 other identifier: NFEC-2024-057
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a single-center, single-arm study. All subjects will receive the same treatment. Children and adolescents (7-20 years old) with migraine who met the inclusion criteria will be enrolled as subjects in the experimental group, and the changes in headache scores before and after the intervention will be compared. The intervention method is as follows: ictal intervention, in which subjects will be evaluated for headache improvement after a short intervention during an acute exacerbation. By wearing a vagus stimulator, the stimulating electrode will be located in the concha region rich in vagus nerve fiber endings, and the appropriate stimulation intensity will be adjusted for stimulation. Therefore, this study will verify the effect of nVNS on the acute treatment of primary headache in children and adolescents. Based on the electrocardiogram and electromyography indicators during the intervention process of nVNS, an objective evaluation system for the improvement of headache by nVNS is established, and the role of stimulation parameters on the effect is further explored to realize the optimization of parameters.

Conditions

Primary Headache; Migraine in Adolescence; Migraine in Children; Cluster Headache; Tension Headache

Keywords

Primary headache; Adolescents; Noninvasive vagus nerve stimulation

Outcome Measures

Primary Outcomes (1)

• Reduction in pain intensity--actue period study

  The visual analogue scale (VAS) was used to evaluate the pain. It is widely used in clinical practice in China. The basic method is to use a swimming ruler of about 10cm in length, marked with 10 scales on one side, and "0" and "10" scales on both ends. For the AP study, the primary outcome measure is the reduction in pain intensity assessed by VAS 2 hours after treatment.

  2 hours after treatment

Secondary Outcomes (3)

• Heart rate variability(HRV)--actue period study and preventive period study

  before and after the intervention. The test consisted of 5 mins of rest (i.e., no vagal stimulation), 10 mins of vagal stimulation, 5 mins of rest, and a total of 20 minutes of electrocard

• Electromyography(EMG)--actue period study and preventive period study

  before and after the intervention. The test consisted of 5 mins of rest (i.e., no vagal stimulation), 10 mins of vagal stimulation, 5 mins of rest, and a total of 20 minutes of electrocard

• Change in pain intensity--actue period study

  half hour, 8-12 hours, 24 hours, and 36-48 hours after treatment

Study Arms (1)

Acute exacerbation experimental group

EXPERIMENTAL

VAS pain intensity will be assessed at the onset of headache, and patients will receive nVNS for half an hour within 20 minutes of the onset, and post-treatment evaluation results will be recorded immediately after treatment, 2 hours, 8-12 hours, 24 hours, and 36-48 hours. During the course of treatment and intervention, a 20-minute ECG closed-loop assessment test will be performed before admission and after return. The procedure included: 5 minutes of rest (i.e. no vagal stimulation), 10 minutes of vagal stimulation, 5 minutes of rest(5-10-5), a total of 20 minutes of ECG, and real-time extraction of heart rate and sex data. Neck electromyography before and after intervention was also used as an auxiliary indicator.

Device: Transcutaneous auricular vagus nerve stimulation

Interventions

Transcutaneous auricular vagus nerve stimulation DEVICE

The vagus nerve's auricular branch is primarily distributed in the tragus, tragus sulcus, and concha cavity. It can activate the nucleus tractus solitarius through the vagus afferent fibers, thereby activating various areas of the vagus nerve in the central nervous system. This stimulation technique involves applying a constant current of around 2-3mA to the epidermal terminals of the ear using an electrode. It aims to regulate the vagus nerve, modulate the autonomic nervous system, release neurotransmitters, improve cerebral blood flow, and alleviate headache symptoms. In the implementation, non-invasive transcutaneous vagus nerve stimulation was performed by having the subject wear a vagus stimulator and adjusting the appropriate stimulation intensity.

Acute exacerbation experimental group

Eligibility Criteria

• Age: 7 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients with migraine, cluster headache and tension-type headache were diagnosed according to Chinese Guidelines for the diagnosis and Treatment of Migraine (2022 edition) and Chinese Guidelines for the diagnosis and treatment of cluster headache (2022 edition).
• Age \>=7 years old, \<=20 years old;
• Patients have experienced headache on 3-15 days per month in the past;
• Maintain a stable dose and frequency of medication and do not take new drugs during the course of participating in the trial;
• They volunteered to participate in the trial and signed informed consent.

You may not qualify if:

• History of secondary headache, aneurysm, intracranial hemorrhage, brain tumor, severe head trauma, drug abuse, addiction, syncope, or seizures;
• prior migraine-preventive surgery, cervical vagotomy, or implantation of an electronic or neurostimulator device;
• Simultaneous use of other devices (e.g., TENS devices, muscle stimulators);
• An implantable medical device in use, such as a pacemaker, hearing aid, or any implantable electronic device;
• underwent head and neck nerve block within the past 2 months;
• Opioid use (more than 2 days per month); Use of analgesics alone or non-steroidal anti-inflammatory drugs (more than 15 days per month); Or tamoxifen, ergots or combination analgesics (more than 10 days per month);
• Patients who underwent cervical vagotomy (cervical vagotomy);
• Pediatric patients (under 6 years old); Pregnant women;
• Patients with clinically significant hypertension, hypotension, bradycardia or tachycardia;
• Patients with congenital heart disease;
• Mental/cognitive disorders, etc.

Sponsors & Collaborators

• Nanfang Hospital, Southern Medical University: lead
• BrainClos Company, LTD.: collaborator
• Zhuhai Fudan Innovation Institute: collaborator

Study Sites (1)

Nanfang Hospital, Southern Medical University

Guangzhou, Guangdong, China

RECRUITING

Related Publications (5)

• Martelletti P, Barbanti P, Grazzi L, Pierangeli G, Rainero I, Geppetti P, Ambrosini A, Sarchielli P, Tassorelli C, Liebler E, de Tommaso M; PRESTO Study Group. Correction to: Consistent effects of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine: additional findings from the randomized, sham-controlled, double-blind PRESTO trial. J Headache Pain. 2018 Dec 18;19(1):120. doi: 10.1186/s10194-018-0949-9.

  PMID: 30563446 BACKGROUND

• Diener HC, Goadsby PJ, Ashina M, Al-Karagholi MA, Sinclair A, Mitsikostas D, Magis D, Pozo-Rosich P, Irimia Sieira P, Lainez MJ, Gaul C, Silver N, Hoffmann J, Marin J, Liebler E, Ferrari MD. Non-invasive vagus nerve stimulation (nVNS) for the preventive treatment of episodic migraine: The multicentre, double-blind, randomised, sham-controlled PREMIUM trial. Cephalalgia. 2019 Oct;39(12):1475-1487. doi: 10.1177/0333102419876920. Epub 2019 Sep 15.

  PMID: 31522546 BACKGROUND

• Cao J, Zhang Y, Li H, Yan Z, Liu X, Hou X, Chen W, Hodges S, Kong J, Liu B. Different modulation effects of 1 Hz and 20 Hz transcutaneous auricular vagus nerve stimulation on the functional connectivity of the periaqueductal gray in patients with migraine. J Transl Med. 2021 Aug 17;19(1):354. doi: 10.1186/s12967-021-03024-9.

  PMID: 34404427 BACKGROUND

• Lai YH, Huang YC, Huang LT, Chen RM, Chen C. Cervical Noninvasive Vagus Nerve Stimulation for Migraine and Cluster Headache: A Systematic Review and Meta-Analysis. Neuromodulation. 2020 Aug;23(6):721-731. doi: 10.1111/ner.13122. Epub 2020 Mar 12.

  PMID: 32166843 BACKGROUND

• Weng S, Xiao X, Liang S, Xue Y, Yang X, Ji Y. 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. BMJ Open. 2025 Mar 12;15(3):e092692. doi: 10.1136/bmjopen-2024-092692.

  PMID: 40074270 DERIVED

MeSH Terms

Conditions

Cluster Headache; Tension-Type Headache

Condition Hierarchy (Ancestors)

Trigeminal Autonomic Cephalalgias; Headache Disorders, Primary; Headache Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Ji Ya-Bin, post-doc

  Nanfang Hospital, Southern Medical University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao XueZhen, PhD

CONTACT

+8613425122570; xuezhenxiao@brainclos.com

Ji Ya-Bin, post-doc

CONTACT

+8615913186246; yabinji@126.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 4, 2024
• First Posted: February 26, 2024
• Study Start: December 5, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: August 12, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE

Locations

CN (1)