Evidence map›Paper›PMID 40409681›Full record

ArticleContemporary clinical trials2025

Evaluating brain mechanisms of combined vagus nerve stimulation and mindfulness training for migraine: A randomized 2 × 2 factorial clinical trial protocol.

Zev Schuman-Olivier, Frances Marin, Lillian D Kinder, Michael Datko, Kassandra Round, Sarasa Tohyama, Ronald G Garcia, Randy L Hirschtick, Robert R Edwards, Rebecca Erwin Wells and 8 more

Registry-linked trialAbstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Contemporary clinical trials, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03592329 (Brain Mechanisms of Vagus Nerve Stimulation and Stress Reduction Training for Migraine), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03592329 nacompletednot on this map

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

TypeinterventionalSponsorMassachusetts General HospitalRan2019 to 2025Enrolled193ConditionsMigraineArmsStress Reduction Training A, active tVNS, Stress Reduction Training B, sham tVNS
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Zev Schuman-OlivierCenter for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA. Electronic address: zschuman@cha.harvard.edu.
Frances MarinAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
Lillian D KinderAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
Michael DatkoAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
Kassandra RoundAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Center for Mindfulness and Compassion, Department of Psychiatry, Cambridge Health Alliance, Harvard Medical School, Cambridge, MA, USA.
Sarasa TohyamaAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.
Ronald G GarciaAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; School of Medicine, Universidad de Santander, Bucaramanga, Colombia.
Randy L HirschtickAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Robert R EdwardsDepartment of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Rebecca Erwin WellsDepartment of Neurology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Hsinlin T ChengDepartment of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Riccardo BarbieriAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nouchine HadjikhaniAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marco L LoggiaAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ted J KaptchukDepartment of Medicine, Beth Israel Deaconess Hospital, Harvard Medical School, Boston, MA, USA.
Timothy T HouleDepartment of Anesthesiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Bruce R RosenAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Vitaly NapadowAthinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Funding

Core NIBSP01AT009965 · NCCIH · MASSACHUSETTS GENERAL HOSPITAL · PI NAPADOW, VITALY, ROSEN, BRUCE R · 2018 to 2023
$10.9M
Research Training in Complementary and Integrative MedicineT32AT000051 · NCCIH · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GLORIA Y YEH · 1999 to 2026
$10.2M
The role of neuroinflammation in human peripheral neuropathic painR01AR079110 · NIAMS · MASSACHUSETTS GENERAL HOSPITAL · PI Marco Luciano Loggia, VITALY NAPADOW · 2022 to 2026
$2.9M
Investigating neural mechanisms of interoceptive awareness in migraineR03NS135420 · NINDS · CAMBRIDGE HEALTH ALLIANCE · PI DATKO, MICHAEL · 2024 to 2024
$164k
NCCIH NIH HHS P01 AT009965NCCIH NIH HHS T32 AT000051NIAMS NIH HHS R01 AR079110NINDS NIH HHS R03 NS135420
6 · The paper itself

Abstract

backgroundMigraine is a major cause of disability and efficacious interventions are needed. In this mechanistic study, we investigate the combined, and potentially synergistic, effects of a multimodal intervention combining Mindfulness-Based Stress Reduction (MBSR) and transcutaneous auricular Vagal Nerve Stimulation (taVNS) for migraine.

methodsWe utilize a modified double-blinded, placebo-controlled, 2 × 2 factorial randomized longitudinal design to assess the effects of an 8-week MBSR intervention with concomitant Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) taVNS on migraine pathophysiology primary outcomes. We will enroll 150 patients with migraine (4-20 headache days/month). After a run-in month of daily diaries, we expect to randomly assign N = 96 participants to one of four treatment groups: (1) MBSR+RAVANS taVNS, (2) MBSR+Sham taVNS, (3) Nature Education Control (NEC) + RAVANS taVNS, or (4) NEC + Sham taVNS. Before and after intervention, participants have three in-person assessments (a 7 T MRI scan, an autonomic/sensory testing (AST) visit, and a 3 T PET-MRI scan). The primary outcomes for this study assess (1) central sensitization (brainstem/cortical response to trigeminal sensory afference), (2) autonomic dysfunction (High Frequency-Heart Rate Variability (HF-HRV) response to stressors), and (3) neuroinflammation (PET[

resultsFunded by NIH (P01AT009965), registered (NCT03592329). Final longitudinal outcomes will be collected by May 2025.

conclusionThis mechanistic study is designed to investigate both independent and synergistic neurobiological effects of MBSR and RAVANS taVNS interventions on three distinct pathophysiological mechanisms of migraine. This research will elucidate the mechanistic and potentially synergistic effects of behavioral interventions (e.g., mindfulness) and device-based treatments (e.g., taVNS) for migraine.

Indexed as

BrainMigraine DisordersMindfulnessStress, PsychologicalVagus Nerve StimulationAdultCombined Modality TherapyDouble-Blind MethodFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedRandomized Controlled Trials as TopicMigraineMindfulnessNeuroimagingNeuromodulationPainPathophysiologyVagal nerve stimulation

Identifiers

PMID40409681
PMCPMC12815238

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.