Feasibility Study: fMRI Evaluation of Auricular PENFS for Fibromyalgia

NCT ID: NCT03008837

Last Updated: 2020-07-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 27 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-06-01
• Study Completion Date: 2019-05-31

Brief Summary

Given recent increasing opioid-related deaths and evidence showing against the use of opioids for non-malignant chronic pain, there is growing need for non-narcotic pain management. Fibromyalgia is a difficult to treat chronic pain condition that is often treated with opioids despite existing evidence. The prevalence of fibromyalgia is increased among Veterans returning from the gulf war and is already a significant burden in senior Veterans who may have suffered with chronic pain for decades already. Many treatment options for fibromyalgia carry intolerable side effects. PENFS (percutaneous electrical neural field stimulation) is a FDA-approved, non-pharmacologic therapy that is currently utilized within the military and VA system, but sufficient evidence regarding its outcomes and neural mechanisms have not been adequately investigated. An understanding of its neural underpinnings and analgesic effects could lead to 1) improvements in pain management and quality of life, 2) cost-savings and 3) development of new techniques to address pain.

Detailed Description

BACKGROUND: Fibromyalgia is a chronic pain syndrome that consists of chronic widespread pain, decreased physical function, fatigue, psychoemotional/sleep disturbances, and various somatic complaints, affecting anywhere from 5-10 million Americans, with ~1,500 Veterans carrying a diagnosis of fibromyalgia seen per year at the Atlanta VAMC alone. It is estimated that fibromyalgia costs the American population over $20 billion/year in lost wages and disability. Initial therapies often include complementary and alternative medicine (CAM) therapies, which are generally considered safe, although their efficacy has not been thoroughly evaluated for fibromyalgia. Thus, non-pharmacologic alternatives require more rigorous scientific investigation for the treatment of fibromyalgia. There is evidence to support the use of percutaneous electrical neural stimulation (PENS) in the treatment of pain conditions, which may have increased effects relative to acupuncture based on systematic reviews. While fMRI data for acupuncture and fibromyalgia exists, no such data exists for PENS treatment. An evolved form of PENS, percutaneous electrical neural field stimulation (PENFS) of the auricle is already used in the military and VA systems for the treatment of chronic pain, but evidence regarding its mechanisms and effects is lacking. Stimulation of the vagus nerve, which has auricular branches, has been previously studied for pain relief in fibromyalgia. However, application of PENS-type stimulation to the auricle has not been previously studied with fMRI, and this type of therapy may lead to neural changes worthy of further exploration. OBJECTIVE: To evaluate the feasibility of using fMRI as a biomarker for the neural substrates of pain and functional changes following PENFS treatments. HYPOTHESIS: PENFS will result in decreased functional connectivity between the insula and default mode network as evaluated by fMRI, which will correlate to more significant improvements in pain and function relative to standard therapy for fibromyalgia. METHODS: Subjects who meet study criteria will receive baseline assessments including resting state fMRI, collection of biobehavioural information such as cognitive and psychological assessments on standardized forms, eating, sleeping and drinking habits, Defense and Veterans Pain Rating Scale (DVPRS), arm curl, 30-s chair stand, and pain interference scores. Subjects will be stratified based on age and gender and then divided into standard therapy control (medication management and physical therapy) or PENFS (series of 4, weekly) treatments and assessed for fMRI changes 2 weeks after the final treatment. Pain and function will also be assessed at the 2 weeks, 6 weeks and 12 weeks following the final treatment. CLINICAL RELEVANCE: Auricular PENFS has not been studied with fMRI. Stimulation of the auricle may produce neural changes that differ from traditional therapies. Understanding the underlying neural mechanisms of auricular PENFS could assist in developing targeted treatments for fibromyalgia and chronic pain. Further, if PENFS can significantly improve pain relief and function over standard therapies, it could decrease the need for opioid analgesics and their associated risks, which is a primary objective of the VA Opioid Safety Initiative. The present investigation will not only serve to elucidate neural changes with PENFS, but could be directly applicable to our Veterans suffering from fibromyalgia by providing evidence regarding the relative effectiveness of this already clinically-employed non-pharmacologic treatment (or lack thereof), and result in evidence-based implementation and potential cost savings to the VA system.

Conditions

Fibromyalgia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

PENFS

Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to percutaneous electrical neural field stimulation (PENFS), which involves placement of small electrodes through a similar process to ear acupuncture to the ear. These electrodes are attached to a battery pack that is taped behind the ear and worn for 5-day intervals. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. Device placement (series of 4, weekly) will be performed by an Anesthesiology Pain Clinic provider. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.

Group Type: EXPERIMENTAL

Military Field Stimulator

Intervention Type: DEVICE

The Military Field Stimulator (MFS/Neuro-Stim System), a percutaneous electrical neural field stimulation (PENFS) device evolved from PENS, is currently employed by the United States (US) military and used in the VA (contract number V797D-50453). There is some evidence based on a small trial of 20 postoperative patients that suggests PENS may have greater benefit than acupuncture for acute pain.

Standard Therapy

Veterans with fibromyalgia who meet study criteria and are randomized to standard therapy will receive physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist. fMRI evaluation of neural changes, assessment of function and quality of life improvements will be performed at the beginning and end of the study.

Group Type: ACTIVE_COMPARATOR

Standard Therapy

Intervention Type: OTHER

Standard therapy for fibromyalgia will include physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist.

Interventions

Military Field Stimulator

The Military Field Stimulator (MFS/Neuro-Stim System), a percutaneous electrical neural field stimulation (PENFS) device evolved from PENS, is currently employed by the United States (US) military and used in the VA (contract number V797D-50453). There is some evidence based on a small trial of 20 postoperative patients that suggests PENS may have greater benefit than acupuncture for acute pain.

Intervention Type: DEVICE

Standard Therapy

Standard therapy for fibromyalgia will include physical therapy, medication management through the Anesthesiology Pain Clinic, and referral to a pain psychologist.

Intervention Type: OTHER

Other Intervention Names

MFS, Neuro-Stim System, PENFS

Eligibility Criteria

Inclusion Criteria

• Subjects must be male and female Veterans age 20-60 with a diagnosis of fibromyalgia as diagnosed by a clinician, by chart review, and by the most recent American College of Rheumatology 2010 criteria for the diagnosis of fibromyalgia. 70,71
• Subjects must self-report consistent, daily pain (greater than 5 on the VAS) >90 days.
• Subjects must have intact skin free of infection at the site of implantation.
• Subjects must be willing to participate and understand the consent.
• Subjects must be right-handed in order to provide consistency in brain structure and function.

Exclusion Criteria

• Subjects must not be currently pregnant, since effects of fMRI and electrical current on the developing fetus are not well-known.
• Subjects must not have an implanted electrical device such as a vagal stimulator, pacemaker, or spinal pain pump, which are not compatible with MRI.
• Subjects must not have a history of seizures or neurologic condition that may alter the structure of the brain.
• Subjects must not have a history of drug abuse or severe, uncontrolled psychiatric illness such as schizophrenia or major depressive disorder with suicidal ideation.
• Subjects must not have psoriasis vulgaris or other skin conditions that may increase the risk of infection at the implantation site.
• Subjects must not have severe anxiety, claustrophobia, or other conditions that may prevent their ability to lie at rest in an MRI scanner. This will be determined after discussion with the patient regarding their own perceived ability to lie at rest in an MRI scanner without the use of additional sedating medications.
• Subjects must not introduce new medications or treatments for fibromyalgia symptoms during the course of the study to prevent confounding results.
• Subjects must not have a concurrent autoimmune or inflammatory disease that causes pain such as systemic lupus erythematosus, inflammatory bowel disease or rheumatoid arthritis, since this could decrease the effect of treatment.

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

VA Office of Research and Development

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anna Woodbury, MD

Role: PRINCIPAL_INVESTIGATOR

Atlanta VA Medical and Rehab Center, Decatur, GA

Locations

Atlanta VA Medical and Rehab Center, Decatur, GA

Decatur, Georgia, United States

Countries

United States

References

Gebre M, Woodbury A, Napadow V, Krishnamurthy V, Krishnamurthy LC, Sniecinski R, Crosson B. Functional Magnetic Resonance Imaging Evaluation of Auricular Percutaneous Electrical Neural Field Stimulation for Fibromyalgia: Protocol for a Feasibility Study. JMIR Res Protoc. 2018 Feb 6;7(2):e39. doi: 10.2196/resprot.8692.

Reference Type: BACKGROUND

PMID: 29410385 (View on PubMed)

Woodbury A, Krishnamurthy V, Gebre M, Napadow V, Bicknese C, Liu M, Lukemire J, Kalangara J, Cui X, Guo Y, Sniecinski R, Crosson B. Feasibility of Auricular Field Stimulation in Fibromyalgia: Evaluation by Functional Magnetic Resonance Imaging, Randomized Trial. Pain Med. 2021 Mar 18;22(3):715-726. doi: 10.1093/pm/pnaa317.

Reference Type: DERIVED

PMID: 33164085 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://article.sapub.org/10.5923.j.cmd.20150504.03.html

Peri-Auricular PENFS for Chronic Pain

Other Identifiers

1IK1RX002113-01A2

Identifier Type: NIH

Identifier Source: secondary_id

View Link

F2113-M

Identifier Type: -

Identifier Source: org_study_id