FibromyalgiaNCT04115033
Randomized Controlled Trial of CES for Fibromyalgia
A study testing Alpha-stim in people with Fibromyalgia, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 60 years
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Alpha-stim
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Mar 2020to 30 Sep 2024
- Phase
- Interventional
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Atlanta VA Medical and Rehab Center, Decatur, GA
Decatur, Georgia, 30033-4004
About this study
Official title: Randomized Double-Blind Placebo-Controlled Trial: fMRI Assessment of Cranial Electrical Stimulation for Fibromyalgia in Veterans
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.
Read the 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.
- Conditions
- Fibromyalgia
- Being tested
- Alpha-stim
- Keywords
- Pain, Fibromyalgia, Magnetic Resonance Imaging, Cranial Electrical Stimulation, Myofascial Pain Syndromes, Veterans
- Medical subject headings
- Fibromyalgia, Pain, Myofascial Pain Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Alpha-stimDevice
Also called Alpha-stim, CES
The device for both groups is the Alpha-stim, a FDA-approved device similar to the Military Field Stimulator (MFS/Neuro-Stim System), a cranial electrical stimulation (CES) device.
| Study group | Role | What they receive |
|---|---|---|
| True CES | Experimental | Veterans with fibromyalgia who meet study criteria and are randomized to the experimental group will receive standard therapy in addition to cranial electrical stimulation (CES), which involves transfer of current from the alpha-stim device using earclip electrodes. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. The treatments can be self administered by the participants. The rs-fcMRI evaluation of neural changes and assessment of clinical pain, function, and quality of life will be performed at the beginning and end of the study. Receives: Device: Alpha-stim |
| Sham CES | Sham comparator | Veterans with fibromyalgia who meet study criteria and are randomized to the sham comparator group will receive standard therapy in addition to a CES device that does not deliver active electrical stimulation. The intention of this FDA-approved device is to relieve pain, though data on its effectiveness is still limited. The rs-fcMRI evaluation of neural changes and assessment of clinical pain, function, and quality of life will be performed at the beginning and end of the study. Receives: Device: Alpha-stim |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Pain Change
For subjects with fibromyalgia, clinical pain was assessed in both groups using the Defense Veterans Pain Rating Scale (DVPRS), a validated measurement tool for pain, as well as analgesic consumption. Clinical pain was measured at baseline, 6 weeks following treatment, and 12 weeks following treatment completion in both groups. Mean differences were measured between the baseline score and the 12-week score. The DVPRS is a combination of several different pain scales including the VAS, verbal rating scale, FACES scale, and numerical rating scale. Measurements will be graded on a scale of 0-10 with 0 being "no pain" and 10 being "severe" or "worst pain."
Measured: baseline, 6 weeks into treatment, and 12 weeks post treatment
Secondary outcomes (5)
Change in Rs-fcMRI Connectivity Effect Size
The region of interest (ROI) was the right Cerebellar 7b seed, and a 2x2 mixed ANOVA interaction was conducted with Family -Wise Error (FWE) constraints to control for multiple comparisons. Voxel threshold was set to p<0.005 uncorrected, cluster threshold of p<0.05 FWE corrected. A Fisher-transform z-score represents the mean connectivity values for each covariate in the model (i.e. groups) for each significant cluster. A z-score value of 0 indicates no difference in functional connectivity. Positive z-scores denote stronger, and negative z-scores weaker, connectivity with the ROI; further research is needed to determine their clinical implications and whether these changes denote a positive or negative outcome.
Measured: baseline, 6 weeks into treatment, and 12 weeks post treatment (change from baseline to 12 weeks post reported)
Sit-to-stand
Tests of function (sit-to-stand, bicep curl, handgrip strength) was performed in both groups at baseline, 6 weeks, and 12 weeks following treatment. Mean difference was measured between baseline and 12 weeks. The sit-to-stand test tests how many full sit-to-stands a subject can perform within a 30 second interval.
Measured: baseline, 6 weeks into treatment, and 12 weeks post treatment
Bicep-curl
Tests of function (sit-to-stand, bicep curl, handgrip strength) was performed in both groups at baseline, 6 weeks, and 12 weeks following treatment. Mean difference was measured between baseline and 12 weeks. The bicep curl tests how many full bicep curls with gender specific weights (8 pounds for male, 5 pounds for female) a subject can perform within a 30 second interval. Both arms were tested.
Measured: baseline, 6 weeks into treatment, and 12 weeks post treatment
Handgrip Strength
Tests of function (sit-to-stand, bicep curl, handgrip strength) was performed in both groups at baseline, 6 weeks, and 12 weeks following treatment. Mean difference was measured between baseline and 12 weeks. The handgrip strength test uses a dynamometer to gauge the pressure that a subject can apply with their handgrip. Both hands were tested.
Measured: baseline, 6 weeks into treatment, and 12 weeks post treatment
PROMIS Change
NIH Patient-Reported Outcomes Measurement Information System (PROMIS) measures were assessed using a validated survey created from independently validated NIH survey questions in both groups. Mean differences in T-scores were measured between the baseline visit and the 12-week visit. PROMIS measures included: PROMIS Item Bank v1.0 - Fatigue - Short Form 6a, PROMIS Item Bank v1.0 - Emotional Distress-Depression - Short Form 4a, PROMIS Item Bank v.1.0 - Emotional Distress - Anxiety- Short Form 7a. For each measure, a lower T-score represents a better clinical outcome.
All of the PROMIS measures reported (Fatigue, Depression, and Anxiety) have been standardized to have a mean of 50 and an SD of 10. This standardization means that a score of 50 is the average level in the population, and any 10-point change in either direction (greater or lesser) represents one SD difference.
Measured: baseline visit and 12 weeks post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2019
- Study start2 Mar 2020
- Primary completion30 Sep 2024
- Study completion30 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Anna Woodbury, MD, Principal investigator, Atlanta VA Medical and Rehab Center, Decatur, GA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04115033
- Sponsor's protocol ID
- B3227-W
- Other IDs
- 1IK2RX003227-01
- Status last verified
- May 2026
- First submitted
- 2 Oct 2019
- Last updated
- 22 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No