Primary HeadacheNCT06277063
nVNS for the Prevention and Treatment of Primary Headache
A study testing Transcutaneous auricular vagus nerve stimulation in people with Primary Headache and Migraine in Adolescence, run by Nanfang Hospital, Southern Medical University at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 7 to 20 years
- Conditions the study is for
- Primary Headache, Migraine in Adolescence, Migraine in Children
- What is being tested?
- Transcutaneous auricular vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 5 Dec 2024to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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);
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Nanfang Hospital, Southern Medical University
Guangzhou, Guangdong
Ji Ya-Bin, post-doc, +8615913186246, yabinji@126.com
About this study
Official title: Noninvasive Vagus Nerve Stimulation for the Prevention and Treatment of Primary Headache: a Single-arm Single-center Clinical Trial.
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
- Being tested
- Transcutaneous auricular vagus nerve stimulation
- Keywords
- Primary headache, Adolescents, Noninvasive vagus nerve stimulation
- Medical subject headings
- Cluster Headache, Tension-Type Headache
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous auricular vagus nerve stimulationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Device: Transcutaneous auricular vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 hours after treatment
Secondary outcomes (3)
Heart rate variability(HRV)--actue period study and preventive period study
A 20-minute closed-loop ECG assessment test was performed before and after the intervention for both the AP study and PP study. The test consisted of 5 minutes of rest (i.e., no vagal stimulation), 10 minutes of vagal stimulation, 5 minutes of rest, and a total of 20 minutes of electrocard.
Measured: 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
A 20-minute closed-loop evaluation test of neck electromyography was performed before and after the intervention for both the AP study and PP study. The testing process consisted of 5 minutes of rest (i.e., no vagal stimulation), 10 minutes of vagal stimulation, 5 minutes of rest, and a total of 20 minutes of electrocard.
Measured: 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
For the AP study, we will analysis the change in pain intensity assessed by VAS scores, half hour, 8-12 hours, 24 hours, and 36-48 hours after treatment.
Measured: half hour, 8-12 hours, 24 hours, and 36-48 hours after treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start5 Dec 2024
- Primary completion31 Aug 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Primary HeadacheStudies of the same condition, open and under way.
- More trials run by Nanfang Hospital, Southern Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nanfang Hospital, Southern Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- BrainClos Company, LTD., Zhuhai Fudan Innovation Institute
- Responsible party
- Sponsor
- Investigators
- Ji Ya-Bin, post-doc, Principal investigator, Nanfang Hospital, Southern Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06277063
- Sponsor's protocol ID
- NFEC-2024-057
- Status last verified
- Aug 2025
- First submitted
- 4 Feb 2024
- Last updated
- 12 Aug 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Publications
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.
PubMed 30563446Diener 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.
PubMed 31522546Cao 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.
PubMed 34404427Lai 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.
PubMed 32166843Weng 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.
PubMed 40074270
Study at a glance
From the registry record, last updated by the sponsor on 12 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Noninvasive Vagus Nerve Stimulation for the Prevention and Treatment of Primary Headache: a Single-arm Single-center Clinical Trial.
- ClinicalTrials.gov ID
- NCT06277063
- Acronym / sponsor ID
- NFEC-2024-057
- Conditions
- Primary Headache, Migraine in Adolescence, Migraine in Children, Cluster Headache, Tension Headache
- Keywords
- Primary headache, Adolescents, Noninvasive vagus nerve stimulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Nanfang Hospital, Southern Medical UniversityUniversity, hospital or other
- Collaborators
- BrainClos Company, LTD., Zhuhai Fudan Innovation Institute
- Study start
- 5 Dec 2024 (actual)
- Primary completion
- 31 Aug 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 26 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Acute exacerbation experimental group | Experimental | Device: Transcutaneous auricular vagus nerve stimulationVAS 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. |
Who may qualify
- Ages
- 7 to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (11 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous auricular vagus nerve stimulationThe 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. | Device | Acute exacerbation experimental group |
Primary outcome
Reduction in pain intensity--actue period study
Time frame: 2 hours after treatment
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.
3 secondary outcomes
Heart rate variability(HRV)--actue period study and preventive period study
Time frame: 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
Time frame: 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
Time frame: half hour, 8-12 hours, 24 hours, and 36-48 hours after treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2025.
- Background: PubMed 30563446Martelletti 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.
- Background: PubMed 31522546Diener 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.
- Background: PubMed 34404427Cao 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.
- Background: PubMed 32166843Lai 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.
- Derived from this study: PubMed 40074270Weng 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.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ji Ya-Bin, post-doc principal investigator
Nanfang Hospital, Southern Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous auricular vagus nerve stimulation in people with Primary Headache and Migraine in Adolescence, run by Nanfang Hospital, Southern Medical University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Xiao XueZhen, PhD (+8613425122570, xuezhenxiao@brainclos.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reduction in pain intensity--actue period study (time frame: 2 hours after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06277063, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Aug 2025.