Vagus Nerve Stimulation and Stress Reduction Training for Migraine

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Migraine

Intervention / Treatment
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* Behavioral: Stress Reduction Training A
* Device: active tVNS
* Behavioral: Stress Reduction Training B
* Device: sham tVNS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activity changes in migraine patients in response to treatment | fMRI BOLD signal (percent BOLD signal change) from baseline to post-treatment, compared across treatment groups. | 8 weeks post treatment | 
| Brain inflammation changes in migraine patients in response to treatment | PET [11C]PBR28 signal, quantified as Standardized Uptake Value (SUV; i.e., tissue radioactivity / injected dose / weight) change from baseline to post-treatment, compared across treatment groups for migraine patients. | 8 weeks post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brain activity differences between Migraine patients and healthy controls | fMRI BOLD signal differences (percent BOLD signal change) between group maps for migraine patients and healthy controls at baseline | 3 weeks | 
| Brain inflammation differences between Migraine patients and healthy controls | PET [11C]PBR28 signal, quantified as Standardized Uptake Value (SUV; i.e., tissue radioactivity / injected dose / weight), differences between healthy controls and migraine patients at baseline. | 3 weeks |