Auricular Neuromodulation in Veterans With Fibromyalgia

BACKGROUND: In the setting of the opioid epidemic, it is crucial to develop and assess non-pharmacologic treatments for pain and understand underlying mechanisms. In the present investigation, the investigators assess a novel non-pharmacologic approach to chronic pain treatment in Veterans suffering from fibromyalgia (a notoriously difficult to treat pain syndrome that affects 5-10 million Americans and disproportionately affects those returning from the Gulf War), utilizing brain imaging as a biomarker and heart rate variability (HRV) to assess a vagal mechanism. Preliminary results from prior VA-funded feasibility study reveal a trend towards improved pain and function with a FDA-approved, non-pharmacologic therapy - auricular percutaneous electrical nerve field stimulation (PENFS) - over standard therapy control for Veterans suffering from fibromyalgia, correlating to altered network connectivity on rs-fcMRI (resting state functional connectivity MRI). PENFS-related improvements continued through 12 weeks following the completion of treatment and correlated to changes in cross-network connectivity, which differed between groups. Based on the preliminary data, the investigators now intend to rigorously assess the treatment effects of PENFS in a large, double-blind, randomized, sham-controlled study.

OBJECTIVE: The proposed Merit, a randomized, sham-controlled trial of auricular PENFS, evaluates the clinical utility of PENFS for fibromyalgia as compared to sham placebo control, acute and longitudinal PENFS-related neural changes visualized on rs-fcMRI and effects of PENFS on HRV as a potential vagal mechanism of pain relief.

HYPOTHESIS: True PENFS results in non-placebo-related short-and long-term pain and physical function improvements that can be correlated with altered connectivity and HRV.

METHODS: For Aim 1, 240 total participants meeting 2016 diagnostic criteria for fibromyalgia (male and female, age 18-60 years old) will be randomized to either true (n=120) or sham (n=120) auricular PENFS.

Neuroimaging data, self-reported pain, and physical function will be assessed at baseline and at 1- and 12- weeks post-treatment to evaluate neural correlates of PENFS-related treatment. Participants who meet study criteria will be randomized to either true or sham PENFS (series of 4, weekly) treatments and assessed for rsfcMRI and functional changes at 1- and 12-weeks post-treatment. Baseline and follow-up rs-fcMRI will be utilized to identify biomarkers of fibromyalgia and PENFS treatment effects for Aim 2 in a subset of 62 participants from Aim 1 who qualify for MRI procedures. Cardiopulmonary data will be simultaneously collected during rs-fcMRI and utilized for the exploratory Aim 3 to evaluate potential PENFS effects on HRV as an outcome measure for vagal effects. In the initial phase preliminary analytical validation will be accomplished in the first 30 participants following IRB approval, hiring and training of staff, and establishment of an image processing pipeline. If initial milestones are met, the rigorous, double-blind, sham-controlled study in a larger group of Veterans will continue. Veterans who are initially assigned to sham placebo PENFS and are not identified as placebo-responders will be offered the opportunity to test the true PENFS device. This study addresses the critical need to clinically evaluate non-pharmacologic therapies for chronic pain.

• PENFS effects on parasympathetic tone as measured by heart rate variability (HRV) [Time frame: Baseline, 12 weeks post-treatment]
• Changes in Fibromyalgia Severity (FIQ-R) [Time frame: Through study completion, an average of 1 year]
• Functional Improvements (Arm curls) [Time frame: Through study completion, an average of 1 year]
• Changes in Fibromyalgia Severity (PSD) [Time frame: Through study completion, an average of 1 year]
• Patient Reported Improvements (PROMIS change) [Time frame: Through study completion, an average of 1 year]
• Functional Improvements (30-s chair stand) [Time frame: Through study completion, an average of 1 year]
• rs-fcMRI as a biomarker of treatment response [Time frame: Baseline, 12 weeks post-treatment]