Migraine
Conditions
Brief 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.
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.
Interventions
BEHAVIORALStress Reduction Training A
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
DEVICEactive tVNS
non-painful electrical stimulation of the auricle
BEHAVIORALStress Reduction Training B
twice weekly "booster" sessions and weekly instructor-led sessions for 8 weeks plus home practice sessions
DEVICEsham tVNS
sham stimulation
Sponsors
Massachusetts General Hospital
National Institutes of Health (NIH)
National Center for Complementary and Integrative Health (NCCIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Brain Activity Changes in Migraine Patients in Response to Treatment | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Activity Differences Between Migraine Patients and Healthy Controls | 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. |
| Brain Inflammation Differences Between Migraine Patients and Healthy Controls | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORVitaly Napadow, PhD,Lic.Ac.
Massachusetts General Hospital
Participant flow
Recruitment details
Participants were recruited through the Mass General Brigham (MGB) Rally for Research platform, MGB Research Participant Data Registry (RPDR), Facebook ads, referrals from providers at MGB and CHA, and flyers. Participants were recruited from Massachusetts and surrounding states, primarily in the Boston area. The recruitment period occurred from August 2019 to November 2024.
Pre-assignment details
Participants completed a daily headache log run-in to assess eligibility prior to randomization. Participants were excluded if they reported fewer than 4 or greater than 20 headache days within a 28-day period. Final eligibility was assessed by doctoral-level review, and eligible participants were randomized to one of 4 study arms. In total, 193 participants began the run-in period; 14 healthy controls and 43 migraine participants were found ineligible and excluded prior to randomization.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 33.9 years STANDARD_DEVIATION 12.2 |
| Disease Duration | 17.5 years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 119 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Headache frequency | 7.4 Days STANDARD_DEVIATION 5.3 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 16 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 23 Participants |
| Sex: Female, Male Female | 26 Participants |
| Sex: Female, Male Male | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| other Total, other adverse events | 14 / 25 | 12 / 28 | 18 / 25 | 13 / 29 | 6 / 29 |
| serious Total, serious adverse events | 0 / 25 | 2 / 28 | 0 / 25 | 0 / 29 | 0 / 29 |
Outcome results
None listed