Auricular Neuromodulation for Fibromyalgia

Overseen By Anna M Ree, BA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: VA Office of Research and Development

Disqualifiers: Pregnancy, Seizures, Claustrophobia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 7

Duration: 4 weeks

240 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It focuses on testing a non-drug therapy, so it's best to ask the trial coordinators for specific guidance.

What data supports the effectiveness of the treatment Percutaneous electrical nerve field stimulation (PENFS) for fibromyalgia?

Research shows that auricular percutaneous electrical nerve field stimulation (PENFS) can change brain structures and chemicals in veterans with fibromyalgia, suggesting it might help manage symptoms. Additionally, similar treatments like non-invasive neuro-adaptive electrostimulation have been shown to reduce pain and disability in fibromyalgia patients. ^{1 2 3 4 5}

Is auricular neuromodulation safe for humans?

The research does not provide specific safety data for auricular neuromodulation, but it mentions that current therapies for fibromyalgia often come with significant risks, suggesting a need for safer alternatives like non-invasive treatments. ^{1 2 4 6 7}

How is the treatment Auricular Neuromodulation for Fibromyalgia different from other treatments?

Auricular Neuromodulation for Fibromyalgia uses a unique approach called percutaneous electrical nerve field stimulation (PENFS), which involves applying electrical stimulation to the ear to influence brain activity and reduce pain. This method is different from traditional treatments as it targets nerve pathways directly and is non-invasive, potentially altering brain structures associated with pain perception. ^{1 3 4 5 8}

What is the purpose of this trial?

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.

Research Team

Anna Woodbury, MD

Principal Investigator

Atlanta VA Medical and Rehab Center, Decatur, GA

Eligibility Criteria

This trial is for veterans with fibromyalgia, a chronic pain condition. Participants should have symptoms that match the criteria for myofascial pain syndrome or fibromyalgia. Specific eligibility details are not provided but typically include factors like age, overall health, and severity of symptoms.

Inclusion Criteria

My skin is healthy where the PENFS treatment will be applied.

I can safely undergo an MRI.

Right-handedness, to provide consistency in brain structure and function

Exclusion Criteria

Claustrophobia

MRI-incompatible implants, or other conditions incompatible with MRI (only for those who elect to perform MRI)

History of uncontrolled psychiatric illness

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either true or sham auricular PENFS, with the device applied weekly for 4 weeks

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with assessments at 1 week, 12 weeks, and 24 weeks post-treatment

24 weeks

3 visits (in-person)

Open-label extension (optional)

Participants initially assigned to sham placebo PENFS and not identified as placebo-responders may opt to test the true PENFS device

Treatment Details

Interventions

• Percutaneous electrical nerve field stimulation

Trial Overview The study tests PENFS (percutaneous electrical nerve field stimulation), an FDA-approved therapy similar to acupuncture but on the ear. It aims to improve pain and physical function by stimulating nerves. The effectiveness will be measured using MRI scans that assess brain activity at rest.

Participant Groups

Group I: True PENFS Active Control 1 Intervention

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.

Group II: Sham PENFS Placebo Group 1 Intervention

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.

Percutaneous electrical nerve field stimulation is already approved in United States for the following indications:

Approved in United States as IB-Stim for:

• Functional abdominal pain associated with irritable bowel syndrome (IBS) in patients 11-18 years of age

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Findings from Research

In a study involving 21 veterans with fibromyalgia, those receiving auricular percutaneous electrical nerve field stimulation (PENFS) showed a trend toward improved pain scores and significant reductions in pain interference with sleep compared to standard therapy alone after 12 weeks.

Neuroimaging results indicated that PENFS treatment was associated with increased connectivity in brain areas related to pain processing and executive control, suggesting a unique mechanism of action for PENFS in managing fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Auricular Field Stimulation in Fibromyalgia: Evaluation by Functional Magnetic Resonance Imaging, Randomized Trial. Woodbury, A., Krishnamurthy, V., Gebre, M., et al.[2023]

Non-invasive neuro-adaptive electrostimulation (NAE) therapy significantly reduced pain in women with fibromyalgia compared to a sham treatment, showing a 3-point improvement on the Visual Analog Scale immediately after the intervention and at 3 months follow-up.

While NAE therapy improved pain and quality of life after 4 weeks, these benefits did not persist at the 3-month follow-up, indicating the need for further research to explore long-term efficacy in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of neuro-adaptive electrostimulation therapy on pain and disability in fibromyalgia: A prospective, randomized, double-blind study. Udina-Cortés, C., Fernández-Carnero, J., Romano, AA., et al.[2021]

In a study of 100 patients with chronic intractable pain, peripheral nerve field stimulation (PNFS) led to an average pain reduction of 4.2 points on an 11-point scale, indicating significant efficacy in pain management.

The treatment was safe, with no long-term complications reported, and 72% of patients reduced their use of analgesics after PNFS, highlighting its potential to improve quality of life and change pain management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature. Verrills, P., Vivian, D., Mitchell, B., et al.[2011]

In a study of 21 veterans with fibromyalgia, those receiving auricular percutaneous electric nerve field stimulation (PENFS) alongside standard therapy showed significant changes in cortical thickness, indicating a potential novel effect of PENFS on brain structure compared to standard therapy alone.

Both treatment groups reported reduced pain, but the ST+PENFS group exhibited specific volumetric changes in brain regions associated with pain processing, suggesting that insular GABA levels and cortical thickness could serve as biomarkers for chronic pain and treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous electric nerve field stimulation alters cortical thickness in a pilot study of veterans with fibromyalgia. Woodbury, A., Krishnamurthy, LC., Bohsali, A., et al.[2023]

A follow-up study of 69 fibromyalgia patients, conducted 45 months after a randomized controlled trial, showed significant long-term improvements in symptoms, with Fibromyalgia Impact Questionnaire scores decreasing from 52.6 at baseline to 31.8 at follow-up (P<.001).

Patients reported lasting benefits from noninvasive cortical stimulation therapy, including reduced medication use and fewer doctor visits for fibromyalgia, indicating the treatment's sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term outcomes in fibromyalgia patients treated with noninvasive cortical electrostimulation. Hargrove, JB., Bennett, RM., Clauw, DJ.[2015]

In a Phase I/II trial involving 14 patients with treatment-resistant fibromyalgia, vagus nerve stimulation (VNS) was found to be generally safe and tolerable, with side effects similar to those seen in epilepsy and depression treatments, including dry mouth and fatigue.

After 3 months of VNS, 5 out of 12 patients showed significant improvement in pain and overall wellness, with some patients even losing their fibromyalgia diagnosis criteria, suggesting VNS could be a promising adjunct treatment for fibromyalgia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. Lange, G., Janal, MN., Maniker, A., et al.[2021]

This study investigates the effects of percutaneous electrical neural field stimulation (PENFS) on fibromyalgia symptoms in 20 adults, aiming to reduce brain connectivity between the default mode network and the insula, which may correlate with pain relief and reduced medication use.

The trial is designed as a feasibility study to assess the practicality of using functional connectivity MRI to explore the neural mechanisms of PENFS, with the goal of informing a larger clinical trial on its efficacy for improving pain and function in fibromyalgia patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional Magnetic Resonance Imaging Evaluation of Auricular Percutaneous Electrical Neural Field Stimulation for Fibromyalgia: Protocol for a Feasibility Study. Gebre, M., Woodbury, A., Napadow, V., et al.[2021]

High-frequency (10 kHz) peripheral nerve stimulation has shown promise in treating facial pain, offering rapid and reversible conduction block in nerves, which may enhance analgesic effects beyond just blocking pain signals.

This technique has advantages over traditional low-frequency stimulation, including the absence of uncomfortable sensations (paresthesias) for patients and the flexibility of electrode placement, making it a potentially more effective and patient-friendly option for pain management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Frequency Peripheral Nerve Stimulation for Craniofacial Pain. Finch, P., Drummond, P.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Feasibility of Auricular Field Stimulation in Fibromyalgia: Evaluation by Functional Magnetic Resonance Imaging, Randomized Trial. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Effects of neuro-adaptive electrostimulation therapy on pain and disability in fibromyalgia: A prospective, randomized, double-blind study. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Peripheral nerve field stimulation for chronic pain: 100 cases and review of the literature. [2011]

4. United States pubmed.ncbi.nlm.nih.gov

Percutaneous electric nerve field stimulation alters cortical thickness in a pilot study of veterans with fibromyalgia. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Long-term outcomes in fibromyalgia patients treated with noninvasive cortical electrostimulation. [2015]

6. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of vagus nerve stimulation in fibromyalgia: a phase I/II proof of concept trial. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Functional Magnetic Resonance Imaging Evaluation of Auricular Percutaneous Electrical Neural Field Stimulation for Fibromyalgia: Protocol for a Feasibility Study. [2021]

8. Switzerland pubmed.ncbi.nlm.nih.gov

High-Frequency Peripheral Nerve Stimulation for Craniofacial Pain. [2021]