Clinical trial NCT06277063: nVNS for the Prevention and Treatment of Primary Headache
Official title: Noninvasive Vagus Nerve Stimulation for the Prevention and Treatment of Primary Headache: a Randomized, Double-blind, Single-center Clinical Trial.
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Primary Headache
Migraine in Adolescence
Migraine in Children
Cluster Headache
Tension Headache
Keywords: Primary headache
Adolescents
Noninvasive vagus nerve stimulation
Lead sponsor: Nanfang Hospital, Southern Medical University
Sponsor class: OTHER
Collaborators: name: BrainClos Company, LTD.
name: Zhuhai Fudan Innovation Institute
First posted: 2024-02-26
Enrollment: 288
Sex: ALL
Minimum age (years): 7
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a single-center, randomized, double-blind controlled study. Patients will be randomly assigned to two groups by envelope drawing. The subjects will be divided into two groups: the acute intervention group and the preventive intervention group. In each group, the subjects will be randomly divided into the experimental group and the control group by means of envelope extraction.

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 attack and preventive 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.


Eligibility criteria: Inclusion Criteria:

1. 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).
2. Age \>=7 years old, \<=20 years old;
3. Patients have experienced headache on 3-15 days per month in the past;
4. Maintain a stable dose and frequency of medication and do not take new drugs during the course of participating in the trial;
5. They volunteered to participate in the trial and signed informed consent.

Exclusion Criteria:

1. History of secondary headache, aneurysm, intracranial hemorrhage, brain tumor, severe head trauma, drug abuse, addiction, syncope, or seizures;
2. prior migraine-preventive surgery, cervical vagotomy, or implantation of an electronic or neurostimulator device;
3. Simultaneous use of other devices (e.g., TENS devices, muscle stimulators);
4. An implantable medical device in use, such as a pacemaker, hearing aid, or any implantable electronic device;
5. underwent head and neck nerve block within the past 2 months;
6. 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);
7. Patients who underwent cervical vagotomy (cervical vagotomy);
8. Pediatric patients (under 6 years old); Pregnant women;
9. Patients with clinically significant hypertension, hypotension, bradycardia or tachycardia;
10. Patients with congenital heart disease;
11. Mental/cognitive disorders, etc.

Primary outcomes:
measure: Reduction in pain intensity--actue period study
timeFrame: 2 hours after treatment
measure: Reduction in the headache attack days during intervention--preventive period study
timeFrame: 4 weeks of baseline, intervention period (5-12 weeks) and post-intervention period (13-20 weeks).
Secondary outcomes:
measure: Heart rate variability(HRV)--actue period study and preventive period study
timeFrame: 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
measure: Electromyography(EMG)--actue period study and preventive period study
timeFrame: 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
measure: Change in pain intensity--actue period study
timeFrame: half hour, 8-12 hours, 24 hours, and 36-48 hours after treatment
measure: Other outcomes for the preventive period study
timeFrame: 4 weeks of baseline, intervention period (5-12 weeks) and post-intervention period (13-20 weeks).
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
Study officials:
affiliation: Nanfang Hospital, Southern Medical University
name: Ji Ya-Bin, post-doc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.