Vagus Nerve Stimulation and Stress Reduction Training for Migraine

February 6, 2026 updated by: Vitaly Napadow, Ph.D., Lic.Ac., Massachusetts General Hospital

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

193

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Massachusetts
      • Charlestown, Massachusetts, United States, 02129
        • Anthinoula A. Martinos Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 61 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Subjects must be between 18 and 65 years of age.
  2. Migraine Diagnosis and general health otherwise.
  3. Willingness to attend twice- weekly treatment session at Cambridge Health Alliance for 8 weeks.
  4. 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.

Exclusion Criteria:

  1. Major illness, psychiatric condition, or neurological disease.
  2. 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
  3. Any condition that would prohibit MRI scanning

Healthy Volunteers have the same eligibility constraints with the addition of current or past history of migraine.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: active tVNS + SRT A
active tVNS and Stress Reduction Training A
Behavioral: Stress Reduction Training A
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
Other Names:
  • SRT A
Device: active tVNS
non-painful electrical stimulation of the auricle
Other Names:
  • transcutaneous vagus nerve stimulation
Experimental: active tVNS + SRT B
active tVNS and Stress Reduction Training B
Device: active tVNS
non-painful electrical stimulation of the auricle
Other Names:
  • transcutaneous vagus nerve stimulation
Behavioral: Stress Reduction Training B
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
Other Names:
  • SRT B
Other: sham tVNS + SRT A
sham stimulation and Stress Reduction Training A
Behavioral: Stress Reduction Training A
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
Other Names:
  • SRT A
Device: sham tVNS
sham stimulation
Other: sham tVNS + SRT B
sham tVNS and Stress Reduction Training B
Behavioral: Stress Reduction Training B
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
Other Names:
  • SRT B
Device: sham tVNS
sham stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
8 weeks (i.e. post-treatment)
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.
8 weeks (post-treatment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Brain Activity Differences Between Migraine Patients and Healthy Controls
Time Frame: 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.
Week 0-3 (Baseline window)
Brain Inflammation Differences Between Migraine Patients and Healthy Controls
Time Frame: 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.
Week 0-3 (Baseline window)

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Primary Clinical Outcome (HIT6)
Time Frame: 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).
8 weeks (post-treatment)
Secondary Clinical Outcome (PCS)
Time Frame: 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).
8 weeks (post-treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Massachusetts General Hospital

Collaborators

National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)

Investigators

  • Principal Investigator: Vitaly Napadow, PhD,Lic.Ac., Massachusetts General Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 20, 2019

Primary Completion (Actual)

January 14, 2025

Study Completion (Actual)

May 29, 2025

Study Registration Dates

First Submitted

May 24, 2018

First Submitted That Met QC Criteria

July 17, 2018

First Posted (Actual)

July 19, 2018

Study Record Updates

Last Update Posted (Actual)

February 25, 2026

Last Update Submitted That Met QC Criteria

February 6, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P001184
  • P01AT009965 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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