Trial Outcomes & Findings for Vagus Nerve Stimulation and Stress Reduction Training for Migraine (NCT NCT03592329)

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.

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.

Measure not collected for some participants.

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).

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.

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.

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.

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).

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).