Clinical trial NCT06415591: Auricular Neuromodulation in Veterans With Fibromyalgia
Official title: Auricular Neuromodulation in Veterans With Fibromyalgia: A Randomized, Sham-Controlled Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fibromyalgia
Keywords: Pain
Fibromyalgia
Magnetic Resonance Imaging
Veterans
Percutaneous Electrical Nerve Field Stimulation
Vagus Nerve
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2024-05-16
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants will be randomized 1:1 to either true or sham PENFS using the auricular device (series of 4, weekly placement with ongoing 5 day (M-F) stimulation - manufacturer recommended) treatments, then assessed for changes in pain and function at 12 and 24 weeks post-treatment. The 12-week time point is chosen to evaluate longer-term neural changes as an indicator of neural plasticity, given the continued improvements seen in the investigators' PENFS group based on preliminary data. The 24- week timepoint is chosen to evaluate longer term (6 months) pain outcomes related to PENFS.
Primary purpose: TREATMENT

Brief summary: PENFS (percutaneous electrical nerve field stimulation) is an FDA-cleared acupuncture-like therapy applied to the external ear targeting several cranial nerve branches including the auricular branch of the vagus nerve to improve pain, physical function, and reduce symptoms of opioid withdrawal. PENFS has been previously shown to provide improvements in fibromyalgia, a difficult to treat chronic pain syndrome, which correlate with changes observed using a special kind of MRI called resting state functional connectivity MRI (rs-fcMRI) that evaluates brain activity at rest. The goals of this study are to rigorously test the initial promising results of PENFS in a much larger group of Veterans suffering from fibromyalgia and to identify potential mechanisms of PENFS effects. Further developing non-pharmacologic therapies for pain can help to improve quality of life and function for those suffering from fibromyalgia and decrease reliance on opioids and other drugs that have numerous side effects for individuals suffering from chronic pain.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age 18 years or older; for those who participate in the MRI portion, age 20-60 years old (limit specifically set for participants receiving an MRI scan; limit set to minimize brain structural changes due to aging)
* For those who participate in the MRI portion, right-handedness, to provide consistency in brain structure and function (limit specifically set for participants receiving an MRI scan; limit set to minimize brain structural changes due to aging)
* For those who participate in the MRI portion, the ability to safely tolerate MRI
* Diagnosis of fibromyalgia by the American College of Rheumatology 2016 criteria69
* Pain score of 4 or greater on DVPRS51 in the 3 months prior to enrollment
* Intact skin in area of PENFS treatment

Exclusion Criteria:

* Pregnancy (self-reported)
* History of seizures or neurologic conditions that alter the brain
* Claustrophobia, MRI-incompatible implants, or other conditions incompatible with MRI (only for those who participate in MRI)
* History of uncontrolled psychiatric illness, autoimmune disease that leads to pain, or skin conditions that can increase risk of infection at PENFS site

Primary outcomes:
measure: Improvements in Clinical Pain (DVPRS)
timeFrame: Through study completion, an average of 1 year
measure: Improvements in Clinical Pain (Self-reported analgesic consumption)
timeFrame: Through study completion, an average of 1 year
Secondary outcomes:
measure: rs-fcMRI as a biomarker of treatment response
timeFrame: Baseline, 12 weeks post-treatment
measure: PENFS effects on parasympathetic tone as measured by heart rate variability (HRV)
timeFrame: Baseline, 12 weeks post-treatment
measure: Changes in Fibromyalgia Severity (FIQ-R)
timeFrame: Through study completion, an average of 1 year
measure: Functional Improvements (Arm curls)
timeFrame: Through study completion, an average of 1 year
measure: Changes in Fibromyalgia Severity (PSD)
timeFrame: Through study completion, an average of 1 year
measure: Patient Reported Improvements (PROMIS change)
timeFrame: Through study completion, an average of 1 year
measure: Functional Improvements (30-s chair stand)
timeFrame: Through study completion, an average of 1 year
Other outcomes:
Locations:
city: Decatur
country: United States
facility: Atlanta VA Medical and Rehab Center, Decatur, GA
state: Georgia
Study officials:
affiliation: Atlanta VA Medical and Rehab Center, Decatur, GA
name: Anna Woodbury, MD
role: PRINCIPAL_INVESTIGATOR
References: