NCT06415591

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
240

participants targeted

Target at P75+ for not_applicable

Timeline
30mo left

Started Nov 2024

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress39%
Nov 2024Nov 2028

First Submitted

Initial submission to the registry

May 8, 2024

Completed
8 days until next milestone

First Posted

Study publicly available on registry

May 16, 2024

Completed
6 months until next milestone

Study Start

First participant enrolled

November 1, 2024

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 1, 2028

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2028

Last Updated

May 22, 2026

Status Verified

May 1, 2026

Enrollment Period

3.8 years

First QC Date

May 8, 2024

Last Update Submit

May 19, 2026

Conditions

Keywords

PainFibromyalgiaMagnetic Resonance ImagingVeteransPercutaneous Electrical Nerve Field StimulationVagus Nerve

Outcome Measures

Primary Outcomes (2)

  • Improvements in Clinical Pain (DVPRS)

    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)

    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 Outcomes (7)

  • PENFS effects on parasympathetic tone as measured by heart rate variability (HRV)

    Baseline, 12 weeks post-treatment

  • Changes in Fibromyalgia Severity (FIQ-R)

    Through study completion, an average of 1 year

  • Functional Improvements (Arm curls)

    Through study completion, an average of 1 year

  • Changes in Fibromyalgia Severity (PSD)

    Through study completion, an average of 1 year

  • Patient Reported Improvements (PROMIS change)

    Through study completion, an average of 1 year

  • +2 more secondary outcomes

Study Arms (2)

True PENFS

ACTIVE COMPARATOR

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

Sham PENFS

SHAM COMPARATOR

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

Interventions

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.

Also known as: PENFS
Sham PENFSTrue PENFS

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, 30033-4004, United States

RECRUITING

Related Publications (1)

  • Vernon M, Rapsas B, Krishnamurthy LC, Krishnamurthy V, Stevens J, Woodbury A. Percutaneous Electrical Nerve Field Stimulation and White Matter Integrity in a Randomized Trial of Veterans With Fibromyalgia. Anesth Analg. 2026 May 1;142(5):1004-1008. doi: 10.1213/ANE.0000000000007785. Epub 2026 Apr 14. No abstract available.

Related Links

MeSH Terms

Conditions

FibromyalgiaPain

Condition Hierarchy (Ancestors)

Muscular DiseasesMusculoskeletal DiseasesRheumatic DiseasesNeuromuscular DiseasesNervous System DiseasesNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and Symptoms

Study Officials

  • Anna Woodbury, MD

    Atlanta VA Medical and Rehab Center, Decatur, GA

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Anna Woodbury, MD

CONTACT

Anna M Ree, BA

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Double-blind, sham placebo controlled. Randomization will be performed by a research coordinator, who will assign each participant a study number and keep a record of whether they are receiving true or sham PENFS, thus maintaining blinding of the participant, the study physicians, the research assistant, and the data analysis team including the P.I. (A.W.) until completion of the follow-up period and data analyses can be performed.
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
FED
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 8, 2024

First Posted

May 16, 2024

Study Start

November 1, 2024

Primary Completion (Estimated)

September 1, 2028

Study Completion (Estimated)

November 1, 2028

Last Updated

May 22, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will not share

Locations