Clinical trial NCT04115033: Randomized Controlled Trial of CES for Fibromyalgia
Official title: Randomized Double-Blind Placebo-Controlled Trial: fMRI Assessment of Cranial Electrical Stimulation for Fibromyalgia in Veterans
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Fibromyalgia
Keywords: Pain
Fibromyalgia
Magnetic Resonance Imaging
Cranial Electrical Stimulation
Myofascial Pain Syndromes
Veterans
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2019-10-03
Enrollment: 50
Sex: ALL
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Cranial electrical stimulation (CES) using a FDA-approved device that uses earclip electrodes to deliver current through the earlobe. The stimulator is meant to stimulate branches of the cranial nerves via the external ear.
Primary purpose: TREATMENT

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. CES (Cranial Electrical 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: RESEARCH PLAN: In the setting of the opioid epidemic, it is crucial to develop non-pharmacologic treatments for pain and biomarkers to accurately assess pain treatment outcomes. In the present investigation, the investigators assess a novel non-pharmacologic approach to chronic pain treatment in patients suffering from fibromyalgia (a notoriously difficult to treat pain syndrome), utilizing neuroimaging as a biomarker. Resting state functional connectivity MRI (rs-fcMRI), a specific neuroimaging technique, has emerged as a reliable research tool to objectively assess, understand, and predict clinical pain in syndromes such as fibromyalgia. Preliminary results reveal a trend towards improved pain and function with a FDA-approved, non-pharmacologic therapy - auricular Cranial Electrical Stimulation (CES) - over standard therapy control, correlating to altered network connectivity on rs-fcMRI. CES-related improvements continued through 12 weeks following the completion of treatment and correlated to changes in cross-network connectivity, which differed between groups. OBJECTIVE: The proposed CDA-2, a randomized, sham-controlled trial of auricular CES, evaluates 1) the clinical utility of CES for fibromyalgia as compared to sham placebo control, 2) short- and long-term CES-related neural changes visualized on rs-fcMRI and 3) the ability of rs-fcMRI to predict CES treatment response. HYPOTHESIS: True CES results in non-placebo-related short- and long-term pain and functional improvements that can be correlated with altered connectivity and predicted by baseline rs-fcMRI. METHODS: Fifty total subjects (male and female Veterans, age 20-60 years old) will be randomized to either sham (n=25) or true (n=25) auricular CES. Neuroimaging data, self-reported pain, and function will be assessed at baseline and at 1 and 12 weeks post-treatment to evaluate neural correlates of CES-related treatment. Subjects who meet study criteria will receive baseline assessments including rs-fcMRI, Defense and Veterans Pain Rating Scale (DVPRS) measures, PROMIS measures, arm curl, 30-s chair stand, handgrip strength tests, and baseline analgesic consumption. Subjects will be block-randomized, stratified based on gender, to either true or sham CES (series of 4, weekly) treatments and assessed for rs-fcMRI and functional changes at 1 and 12 weeks post-treatment. This study addresses the critical need to identify and understand neural correlates of pain and non-opioid pain management.

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.
* 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 electrode placement.
* 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.

Primary outcomes:
measure: Clinical Pain Change
timeFrame: baseline, 1 week following treatment, and 12 weeks following treatment completion
Secondary outcomes:
measure: rs-fcMRI Connectivity Change
timeFrame: baseline, 1 week, and 12 weeks following treatment completion
measure: Sit-to-stand
timeFrame: baseline, 1 week, and 12 weeks following treatment
measure: PROMIS Change
timeFrame: baseline, 1 week, and 12 weeks following treatment
measure: Bicep-curl
timeFrame: baseline, 1 week, and 12 weeks following treatment
measure: Handgrip strength
timeFrame: baseline, 1 week, and 12 weeks following treatment
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: