Auricular Neuromodulation in Veterans With Fibromyalgia (PENFS)

May 19, 2026 updated by: VA Office of Research and Development

Auricular Neuromodulation in Veterans With Fibromyalgia: A Randomized, Sham-Controlled Study

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

240

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Anna M Ree, BA
  • Phone Number: 202561 (404) 321-6111
  • Email: anna.ree@va.gov

Study Locations

  • United States
    • Georgia
      • Decatur, Georgia, United States, 30033-4004
        • Recruiting
        • Atlanta VA Medical and Rehab Center, Decatur, GA
        • Contact:
        • Principal Investigator:
          • Anna Woodbury, MD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: True PENFS
Percutaneous electrical nerve stimulation applied to the ear x 4 over a 4 week period. The device is placed over the area of the ear and worn home continuously for a 5-day period, during which time it stimulates at a pre-set on/off duty cycle. At each in-person visit, the device is replaced until the device has been placed 4 times. The stimulation delivered is below the threshold of sensory perception.
Device: Percutaneous electrical nerve field stimulation
FDA-approved 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.
Other Names:
  • PENFS
Sham Comparator: Sham PENFS
A device is placed at the same points for the same amount of time and at the same intervals as the true device. This device will not deliver electrical stimulation.
Device: Percutaneous electrical nerve field stimulation
FDA-approved 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.
Other Names:
  • PENFS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Improvements in Clinical Pain (DVPRS)
Time Frame: Through study completion, an average of 1 year
The investigators will assess whether pain and functional improvements occur with the application of PENFS. Clinical pain, as measured by the Defense Veterans Pain Rating Scale (DVPRS), will be our primary outcome. This measure is rated on a scale of 0 to 10, with 0 being "no pain" and 10 being "as bad as it could be, nothing else matters". Assessments will be administered at baseline, immediately pre- and post-treatment (the device is replaced every 5 days for a total of 4 device applications), 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year
Improvements in Clinical Pain (Self-reported analgesic consumption)
Time Frame: Through study completion, an average of 1 year
The investigators will assess whether pain and functional improvements occur with the application of PENFS. Changes in clinical pain will also be assessed for this outcome via self-reported analgesic consumption. This measure is not rated on a scale - it is self-reported use. Assessments will be administered at baseline, immediately pre- and post-treatment (the device is replaced every 5 days for a total of 4 device applications), 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
rs-fcMRI as a biomarker of treatment response
Time Frame: Baseline, 12 weeks post-treatment
Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) will be performed at baseline and 12 weeks post-treatment to assess changes in cross-network connectivity with the default mode network (DMN) and sensorimotor network (SMN) as well as connectivity within the salience network (SN).
Baseline, 12 weeks post-treatment
PENFS effects on parasympathetic tone as measured by heart rate variability (HRV)
Time Frame: Baseline, 12 weeks post-treatment
Heart rate variability (HRV) will be assessed at the MRI scans at baseline and 12 weeks post-treatment with an MR-compatible pulse oximeter to evaluate the effects of PENFS on parasympathetic tone.
Baseline, 12 weeks post-treatment
Functional Improvements (Arm curls)
Time Frame: Through study completion, an average of 1 year
Functional improvements will be assessed using the arm curl test. Assessments will be administered at baseline, immediate post-treatment, 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year
Functional Improvements (30-s chair stand)
Time Frame: Through study completion, an average of 1 year
Functional improvements will be assessed using the 30-s chair stand. Assessments will be administered at baseline, immediate post-treatment, 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year
Changes in Fibromyalgia Severity (FIQ-R)
Time Frame: Through study completion, an average of 1 year
Fibromyalgia severity will be assessed via the Fibromyalgia Impact Questionnaire (FIQ-R). Each question is rated on a scale of 1 to 10 with 1 being the least impact/severity and 10 being the most impact/severity. Assessments will be administered at baseline, immediate post-treatment, 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year
Changes in Fibromyalgia Severity (PSD)
Time Frame: Through study completion, an average of 1 year
Fibromyalgia severity will be assessed via the Polysymptomatic Distress Scale (PSD). This measure ranges from scores of 0 to 31, with 0 being the least severe and 31 being the most severe. Assessments will be administered at baseline, immediate post-treatment, 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year
Patient Reported Improvements (PROMIS change)
Time Frame: Through study completion, an average of 1 year
Patient reported improvements will be assessed using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROMIS measures are rated on a scale of 1 to 5 with 1 being the least intense ("Never") and 5 being the most intense ("Always"). Assessments will be administered at baseline, immediate post-treatment, 12 weeks post-treatment, and 24 weeks post-treatment.
Through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

VA Office of Research and Development

Investigators

  • Principal Investigator: Anna Woodbury, MD, Atlanta VA Medical and Rehab Center, Decatur, GA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2024

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

November 1, 2028

Study Registration Dates

First Submitted

May 8, 2024

First Submitted That Met QC Criteria

May 9, 2024

First Posted (Actual)

May 16, 2024

Study Record Updates

Last Update Posted (Actual)

May 22, 2026

Last Update Submitted That Met QC Criteria

May 19, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • F5050-R
  • I01RX005050 (U.S. NIH Grant/Contract: VA RR&D)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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