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NCT03592329

Vagus Nerve Stimulation and Stress Reduction Training for Migraine

Completed NA Results posted Last updated 25 February 2026
What this trial tests

NA trial testing Stress Reduction Training A in Migraine in 193 participants. Completed in 29 May 2025.

Timeline
20 August 2019
Primary endpoint
14 January 2025
29 May 2025

Quick facts

Lead sponsorMassachusetts General Hospital
PhaseNA
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposebasic science
Enrollment193
Start date20 August 2019
Primary completion14 January 2025
Estimated completion29 May 2025
Sites1 location across United States

Drugs / interventions tested

Conditions studied

Sponsor

Massachusetts General Hospital

Who can join

Adults 18 to 65, any sex, with Migraine. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Brain Activity Changes in Migraine Patients in Response to Treatment Primary · 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).

GroupValue95% CI
Active tVNS + MBSR-0.249± 1.17
Active tVNS + NEC0.679± 0.971
Sham tVNS + MBSR0.680± 1.36
Sham tVNS + NEC1.06± 1.36
Brain Inflammation Changes in Migraine Patients in Response to Treatment Primary · 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.

GroupValue95% CI
Active tVNS + MBSR-0.00668± 0.0717
Active tVNS + NEC-0.0113± 0.0709
Sham tVNS + MBSR0.0590± 0.0867
Sham tVNS + NEC Sham tVNS + NEC Sham tVNS + NEC-0.0234± 0.0274
Brain Activity Differences Between Migraine Patients and Healthy Controls Secondary · Week 0-3 (Baseline window)

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.

GroupValue95% CI
Healthy Controls-0.114± 0.131
Migraine Patients0.0146± 0.155
Brain Inflammation Differences Between Migraine Patients and Healthy Controls Secondary · Week 0-3 (Baseline window)

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.

GroupValue95% CI
Healthy Controls0.974± 0.070
Migraine Patients0.989± 0.0875
Primary Clinical Outcome (HIT6) Secondary · 8 weeks (post-treatment)

The Headache Impact Test (HIT-6) is a 6-item self-report evaluation of headache disability. The HIT6 is measured on a scale from 36 to 78 points, with higher scores indicating greater headache-related disability. Participants completed the HIT-6 at baseline and post-treatment. The reported outcome measure is a difference score (post-treatment HIT-6 minus baseline HIT-6).

GroupValue95% CI
Active tVNS + MBSR-5.05± 4.67
Active tVNS + NEC-1.17± 5.90
Sham tVNS + MBSR-2.6± 3.14
Sham tVNS + NEC-3.61± 4.69
Secondary Clinical Outcome (PCS) Secondary · 8 weeks (post-treatment)

The Pain Catastrophizing Scale (PCS) is a 13-item evaluation of a participant's subjective pain experience. The PCS is measured on a scale from 0 to 52 points, with higher scores indicating a greater degree of pain catastrophizing. The PCS includes three subscales (Rumination, Magnification, and Helplessness), and the scores from the subscales were summed to determine the total score. Participants completed the PCS at baseline and post-treatment. The reported outcome measure is a difference score (post-treatment PCS minus baseline PCS).

GroupValue95% CI
Active tVNS + MBSR-5.26± 5.69
Active tVNS + NEC-1.48± 4.89
Sham tVNS + MBSR-0.47± 4.87
Sham tVNS + NEC-3.94± 4.58

Adverse events — posted to ClinicalTrials.gov

Time frame: Adverse event data were collected over the 6 months that participants were in the study.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Active tVNS + MBSR
Serious: 0/25 (0%)
Deaths: 0
Active tVNS + NEC
Serious: 2/28 (7%)
Deaths: 0
Sham tVNS + MBSR
Serious: 0/25 (0%)
Deaths: 0
Sham tVNS + NEC
Serious: 0/29 (0%)
Deaths: 0
Healthy Controls
Serious: 0/29 (0%)
Deaths: 0

Serious adverse events (2 terms)

ReactionSystemActive tVNS + MBSRActive tVNS + NECSham tVNS + MBSRSham tVNS + NECHealthy Controls
SurgerySurgical and medical procedures
Kidney InfectionRenal and urinary disorders
Other adverse events (16 terms — click to expand)

ReactionSystemActive tVNS + MBSRActive tVNS + NECSham tVNS + MBSRSham tVNS + NECHealthy Controls
DizzinessGeneral disorders
AnxietyPsychiatric disorders
Skin ConditionSkin and subcutaneous tissue disorders
Muscle PainMusculoskeletal and connective tissue disorders
IllnessGeneral disorders
HeadacheNervous system disorders
Arterial Line IssueGeneral disorders
Incidental FindingNervous system disorders
SurgerySurgical and medical procedures
Kidney InfectionRenal and urinary disorders
Stomach PainGastrointestinal disorders
Head InjuryGeneral disorders
InsomniaGeneral disorders
Chest PainCardiac disorders
Ear IssueEar and labyrinth disorders
SyncopeGeneral disorders

Most-reported serious reactions: Surgery, Kidney Infection.

Data from ClinicalTrials.gov NCT03592329 adverse events section.

Sponsor's own description

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.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Mindfulness in migraine: A narrative review.
    Wells RE, Seng EK, Edwards RR, Victorson DE, et al · · 2020 · cited 45× · PMID 31933391 · DOI 10.1080/14737175.2020.1715212
  2. Trigeminal nerve microstructure is linked with neuroinflammation and brainstem activity in migraine.
    Tohyama S, Datko M, Brusaferri L, Kinder LD, et al · · 2025 · cited 11× · PMID 39873385 · DOI 10.1093/brain/awaf029
  3. Evaluating brain mechanisms of combined vagus nerve stimulation and mindfulness training for migraine: A randomized 2 × 2 factorial clinical trial protocol.
    Schuman-Olivier Z, Marin F, Kinder LD, Datko M, et al · · 2025 · PMID 40409681 · DOI 10.1016/j.cct.2025.107947

Verify or expand the search:

Other recruiting trials for Migraine

Currently open trials in the same condition.

Other Massachusetts General Hospital trials

Trials by the same sponsor.

Verify against primary sources

Data sources for this page

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