MigraineNCT03592329

Vagus Nerve Stimulation and Stress Reduction Training for Migraine

A study testing Stress Reduction Training A, active tVNS and Stress Reduction Training B in people with Migraine, run by Massachusetts General Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study design has two components: 1) a cross-sectional assessment of brain activity and inflammation in migraine patients compared to healthy controls and 2) an assessment of 8 weeks of a combination therapy approach to treating migraine. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Migraine
What is being tested?: Stress Reduction Training A, active tVNS and Stress Reduction Training B
Type of treatment: Medical device, Lifestyle or therapy programme
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 193 participants
Where: 1 siteUnited States
Study dates: 20 Aug 2019to 29 May 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

Subjects must be between 18 and 65 years of age.
Migraine Diagnosis and general health otherwise.
Willingness to attend twice- weekly treatment session at Cambridge Health Alliance for 8 weeks.
Able to give written consent and participate in group interventions in English.
Healthy Volunteers between the ages of 18 and 65 can participate in this study.

Who cannot join

Major illness, psychiatric condition, or neurological disease.
Previous experience with stress reduction training (such as mindfulness training, MBSR, MBCT, Relaxation Response) or more than 15 home mediation practice sessions in the past month, or more than 10 classes in yoga, Tai Chi, or Qi Gong in the past 3 months
Any condition that would prohibit MRI scanning
Healthy Volunteers have the same eligibility constraints with the addition of current or past history of migraine.

Trial locations and contacts

1 site in 1 country.

United States1 site

Anthinoula A. Martinos Center
Charlestown, Massachusetts, 02129

Other trials in United States

About this study

Official title: Brain Mechanisms of Vagus Nerve Stimulation and Stress Reduction Training for Migraine

Read the detailed description

Chronic pain is the most prevalent and disabling medical condition, and no single therapy has proven to be completely successful for alleviating pain, such as migraine headache. It is well documented, and recommended in the recent Institute of Medicine (IOM) report, that a multimodal approach is optimal for pain management. This study will evaluate a combination transcutaneous vagus nerve stimulation and stress reduction training for migraine.

Investigators will recruit participants who have migraines and randomize to one of four potential treatment arms (real or sham stimulation + real or sham stress reduction training). Brain imaging (MRI and PET) and clinical data will be collected before and after 8 weeks of the combination therapy.

Healthy controls will also be recruited for collection of the same baseline brain imaging and clinical data, but with no treatment or second data collection phase.

Findings from this research will help elucidate brain activity and inflammation associated with migraines and evaluate the efficacy of the combination therapy in reducing migraine.

Conditions: Migraine
Being tested: Stress Reduction Training A, active tVNS, Stress Reduction Training B, sham tVNS
Medical subject headings: Migraine Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Stress Reduction Training ABehavioural
Also called SRT A
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
active tVNSDevice
Also called transcutaneous vagus nerve stimulation
non-painful electrical stimulation of the auricle
Stress Reduction Training BBehavioural
Also called SRT B
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
sham tVNSDevice
sham stimulation

Study groups in NCT03592329
Study group	Role	What they receive
active tVNS + SRT A	Experimental	active tVNS and Stress Reduction Training A Receives: Behavioral: Stress Reduction Training A; Device: active tVNS
active tVNS + SRT B	Experimental	active tVNS and Stress Reduction Training B Receives: Device: active tVNS; Behavioral: Stress Reduction Training B
sham tVNS + SRT A	Other	sham stimulation and Stress Reduction Training A Receives: Behavioral: Stress Reduction Training A; Device: sham tVNS
sham tVNS + SRT B	Other	sham tVNS and Stress Reduction Training B Receives: Behavioral: Stress Reduction Training B; Device: sham tVNS

What is being measured

The primary outcome is the main question the study is designed to answer.

Brain Activity Changes in Migraine Patients in Response to Treatment
Post-treatment versus baseline change in intervention-evoked cortical amplification ratio (left posterior insula to spinal trigeminal nucleus ratio of fMRI BOLD percent signal change) for trigeminal afferent stimulation (i.e. forehead stimulation).
Measured: 8 weeks (i.e. post-treatment)
Brain Inflammation Changes in Migraine Patients in Response to Treatment
PET [11C]PBR28 signal, quantified as Standardized Uptake Value Ratio (SUVR; i.e., tissue radioactivity / injected dose / weight) change from baseline to post-treatment, compared across treatment groups for migraine patients. [11C]PBR28 SUVR was measured in the insula (average of left and right insula), using cerebellum SUV as a pseudo-reference region.
Measured: 8 weeks (post-treatment)

Secondary outcomes (2)

Brain Activity Differences Between Migraine Patients and Healthy Controls
Amygdala fMRI BOLD signal differences from stressful imagery task (percent BOLD signal change, negative minus neutral image blocks), contrasting migraine patients (at baseline) and healthy controls.
Measured: Week 0-3 (Baseline window)
Brain Inflammation Differences Between Migraine Patients and Healthy Controls
PET [11C]PBR28 signal, quantified as Standardized Uptake Value Ratio (SUVR; i.e., tissue radioactivity / injected dose / weight), differences between healthy controls and migraine patients at baseline. [11C]PBR28 SUVR was measured in the insula (average of left and right insula), using cerebellum SUV as a pseudo-reference region.
Measured: Week 0-3 (Baseline window)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

20 Aug 201929 May 2025

First posted19 Jul 2018
Study start20 Aug 2019
Primary completion14 Jan 2025
Study completion29 May 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MigraineStudies of the same condition, open and under way.
More trials run by Massachusetts General HospitalThe 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: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 193 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03592329
Sponsor's protocol ID: 2018P001184
Other IDs: P01AT009965
Status last verified: Feb 2026
First submitted: 24 May 2018
Last updated: 25 Feb 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingObservational study
Study of the Glymphatic System in Migraine
Migraine
Active, not recruiting
Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
Migraine
Active, not recruiting
App-Based Migraine Treatment: The Health enSuite Study
Migraine, Migraine With Aura
Not yet recruiting
A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
Migraine Disorders
Recruiting
Marine Lipids Ease Painful TMD
Temporomandibular Disorder (TMD)

All Migraine trials

Study at a glance

From the registry record, last updated by the sponsor on 25 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Brain Mechanisms of Vagus Nerve Stimulation and Stress Reduction Training for Migraine
ClinicalTrials.gov ID: NCT03592329
Acronym / sponsor ID: 2018P001184
Conditions: Migraine
Study type: Interventional
Recruitment status: Completed
Enrolment: 193 participants (actual)
Lead sponsor: Massachusetts General HospitalUniversity, hospital or other
Collaborators: National Institutes of Health (NIH), National Center for Complementary and Integrative Health (NCCIH)
Study start: 20 Aug 2019 (actual)
Primary completion: 14 Jan 2025 (actual)
Study completion: 29 May 2025 (actual)
First posted: 19 Jul 2018 (actual)
Results: Posted 25 Feb 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Healthy controls will also be recruited for collection of the same baseline brain imaging and clinical data, but with no treatment or second data collection phase.

Findings from this research will help elucidate brain activity and inflammation associated with migraines and evaluate the efficacy of the combination therapy in reducing migraine.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
active tVNS + SRT A	Experimental	Behavioral: Stress Reduction Training A, Device: active tVNSactive tVNS and Stress Reduction Training A
active tVNS + SRT B	Experimental	Device: active tVNS, Behavioral: Stress Reduction Training Bactive tVNS and Stress Reduction Training B
sham tVNS + SRT A	Other	Behavioral: Stress Reduction Training A, Device: sham tVNSsham stimulation and Stress Reduction Training A
sham tVNS + SRT B	Other	Behavioral: Stress Reduction Training B, Device: sham tVNSsham tVNS and Stress Reduction Training B

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Subjects must be between 18 and 65 years of age.
Migraine Diagnosis and general health otherwise.
Willingness to attend twice- weekly treatment session at Cambridge Health Alliance for 8 weeks.
Able to give written consent and participate in group interventions in English.
Healthy Volunteers between the ages of 18 and 65 can participate in this study.

Key exclusion criteria (4 listed)

Major illness, psychiatric condition, or neurological disease.
Previous experience with stress reduction training (such as mindfulness training, MBSR, MBCT, Relaxation Response) or more than 15 home mediation practice sessions in the past month, or more than 10 classes in yoga, Tai Chi, or Qi Gong in the past 3 months
Any condition that would prohibit MRI scanning
Healthy Volunteers have the same eligibility constraints with the addition of current or past history of migraine.

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
Stress Reduction Training AAlso: SRT Atwice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions	Behavioural	active tVNS + SRT A, sham tVNS + SRT A
active tVNSAlso: transcutaneous vagus nerve stimulationnon-painful electrical stimulation of the auricle	Device	active tVNS + SRT A, active tVNS + SRT B
Stress Reduction Training BAlso: SRT Btwice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions	Behavioural	active tVNS + SRT B, sham tVNS + SRT B
sham tVNSsham stimulation	Device	sham tVNS + SRT A, sham tVNS + SRT B

Primary outcome

Brain Activity Changes in Migraine Patients in Response to Treatment
Time frame: 8 weeks (i.e. post-treatment)
Post-treatment versus baseline change in intervention-evoked cortical amplification ratio (left posterior insula to spinal trigeminal nucleus ratio of fMRI BOLD percent signal change) for trigeminal afferent stimulation (i.e. forehead stimulation).
Brain Inflammation Changes in Migraine Patients in Response to Treatment
Time frame: 8 weeks (post-treatment)
PET [11C]PBR28 signal, quantified as Standardized Uptake Value Ratio (SUVR; i.e., tissue radioactivity / injected dose / weight) change from baseline to post-treatment, compared across treatment groups for migraine patients. [11C]PBR28 SUVR was measured in the insula (average of left and right insula), using cerebellum SUV as a pseudo-reference region.

2 secondary outcomes

Brain Activity Differences Between Migraine Patients and Healthy Controls
Time frame: Week 0-3 (Baseline window)
Brain Inflammation Differences Between Migraine Patients and Healthy Controls
Time frame: Week 0-3 (Baseline window)

Results and safety

Results posted to the registry on 25 Feb 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Active tVNS + MBSR	25	20
Active tVNS + NEC	28	23
Sham tVNS + MBSR	25	18
Sham tVNS + NEC	29	19
Healthy Controls	29	24

Primary outcome: Brain Activity Changes in Migraine Patients in Response to Treatment

Time frame: 8 weeks (i.e. post-treatment). Mean (Standard Deviation). Unit: Log ratio % signal change (Insula/Sp5)

Measure	Active tVNS + MBSR n = 11	Active tVNS + NEC n = 14	Sham tVNS + MBSR n = 14	Sham tVNS + NEC n = 14
Value	-0.249 (1.17)	0.679 (0.971)	0.680 (1.36)	1.06 (1.36)

Population analysed: Only participants who successfully completed a pre- and post-treatment 7T fMRI scan are included in this analysis. Some participants completed the overall study but were excluded from fMRI scanning due to MRI contraindications, e.g. metal implants, claustrophobia.

Primary outcome: Brain Inflammation Changes in Migraine Patients in Response to Treatment

Time frame: 8 weeks (post-treatment). Mean (Standard Deviation). Unit: Uptake ratio

Measure	Active tVNS + MBSR n = 10	Active tVNS + NEC n = 10	Sham tVNS + MBSR n = 5	Sham tVNS + NEC Sham tVNS + NEC Sham tVNS + NEC n = 11
Value	-0.00668 (0.0717)	-0.0113 (0.0709)	0.0590 (0.0867)	-0.0234 (0.0274)

Population analysed: Only participants who successfully completed a pre- and post-treatment 3T PET-MR scan are included in this analysis. Some participants completed the overall study but were excluded from PET-MR scanning due to MRI contraindications (e.g. metal implants, claustrophobia) and/or the presence of the Ala147Thr polymorphism which is associated with low-affinity binding to the radiotracer.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data were collected over the 6 months that participants were in the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events
Active tVNS + MBSR	0 of 25 (0%)	14 of 25 (56%)
Active tVNS + NEC	2 of 28 (7.1%)	12 of 28 (42.9%)
Sham tVNS + MBSR	0 of 25 (0%)	18 of 25 (72%)
Sham tVNS + NEC	0 of 29 (0%)	13 of 29 (44.8%)
Healthy Controls	0 of 29 (0%)	6 of 29 (20.7%)

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

Related trials for Migraine

RecruitingObservational study
Study of the Glymphatic System in Migraine
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Active, not recruiting
Clinical and Neurophysiological Effects of tDCS to Visual and Motor Cortex in Migraine
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App-Based Migraine Treatment: The Health enSuite Study
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A Prospective Study of Rimegepant for Short-term Preventive Treatment of Night-shift-related Migraine in Healthcare Professionals
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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. This study is not recruiting at the moment.

Vitaly Napadow, PhD,Lic.Ac. principal investigator

Massachusetts General Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A study testing Stress Reduction Training A, active tVNS and Stress Reduction Training B in people with Migraine, run by Massachusetts General Hospital at 1 site in United States.

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 4 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: finished, as of the sponsor's last update on 25 Feb 2026. 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 United States. 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?

Yes. Results are posted in the registry (first posted 25 Feb 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Brain Activity Changes in Migraine Patients in Response to Treatment (time frame: 8 weeks (i.e. post-treatment)). The study lists 2 primary outcomes in all. 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 NCT03592329.

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 25 Feb 2026.