Auricular Neuromodulation in Veterans With Fibromyalgia: A Randomized, Sham-Controlled Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 2
- 主要终点
- Improvements in Clinical Pain (DVPRS)
研究概览
简要总结
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.
详细描述
BACKGROUND: In the setting of the opioid epidemic, it is crucial to develop and assess non-pharmacologic treatments for pain and understand underlying mechanisms. In the present investigation, the investigators assess a novel non-pharmacologic approach to chronic pain treatment in Veterans suffering from fibromyalgia (a notoriously difficult to treat pain syndrome that affects 5-10 million Americans and disproportionately affects those returning from the Gulf War), utilizing brain imaging as a biomarker and heart rate variability (HRV) to assess a vagal mechanism. Preliminary results from prior VA-funded feasibility study reveal a trend towards improved pain and function with a FDA-approved, non-pharmacologic therapy - auricular percutaneous electrical nerve field stimulation (PENFS) - over standard therapy control for Veterans suffering from fibromyalgia, correlating to altered network connectivity on rs-fcMRI (resting state functional connectivity MRI). PENFS-related improvements continued through 12 weeks following the completion of treatment and correlated to changes in cross-network connectivity, which differed between groups. Based on the preliminary data, the investigators now intend to rigorously assess the treatment effects of PENFS in a large, double-blind, randomized, sham-controlled study.
OBJECTIVE
The proposed Merit, a randomized, sham-controlled trial of auricular PENFS, evaluates the clinical utility of PENFS for fibromyalgia as compared to sham placebo control, acute and longitudinal PENFS-related neural changes visualized on rs-fcMRI and effects of PENFS on HRV as a potential vagal mechanism of pain relief.
HYPOTHESIS
True PENFS results in non-placebo-related short-and long-term pain and physical function improvements that can be correlated with altered connectivity and HRV.
METHODS: For Aim 1, 240 total participants meeting 2016 diagnostic criteria for fibromyalgia (male and female, age 18-60 years old) will be randomized to either true (n=120) or sham (n=120) auricular PENFS.
Neuroimaging data, self-reported pain, and physical function will be assessed at baseline and at 1- and 12- weeks post-treatment to evaluate neural correlates of PENFS-related treatment. Participants who meet study criteria will be randomized to either true or sham PENFS (series of 4, weekly) treatments and assessed for rsfcMRI and functional changes at 1- and 12-weeks post-treatment. Baseline and follow-up rs-fcMRI will be utilized to identify biomarkers of fibromyalgia and PENFS treatment effects for Aim 2 in a subset of 62 participants from Aim 1 who qualify for MRI procedures. Cardiopulmonary data will be simultaneously collected during rs-fcMRI and utilized for the exploratory Aim 3 to evaluate potential PENFS effects on HRV as an outcome measure for vagal effects. In the initial phase preliminary analytical validation will be accomplished in the first 30 participants following IRB approval, hiring and training of staff, and establishment of an image processing pipeline. If initial milestones are met, the rigorous, double-blind, sham-controlled study in a larger group of Veterans will continue. Veterans who are initially assigned to sham placebo PENFS and are not identified as placebo-responders will be offered the opportunity to test the true PENFS device. This study addresses the critical need to clinically evaluate non-pharmacologic therapies for chronic pain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
True PENFS
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.
干预措施: Percutaneous electrical nerve field stimulation (Device)
Sham PENFS
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.
干预措施: Percutaneous electrical nerve field stimulation (Device)
结局指标
主要结局
Improvements in Clinical Pain (DVPRS)
时间窗: Through study completion, an average of 1 year
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.
Improvements in Clinical Pain (Self-reported analgesic consumption)
时间窗: Through study completion, an average of 1 year
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.
rs-fcMRI as a biomarker of treatment response
时间窗: Baseline, 12 weeks post-treatment
Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) will be performed at baseline and 12 weeks post-treatment to assess changes in cross-network connectivity with the default mode network (DMN) and sensorimotor network (SMN) as well as connectivity within the salience network (SN).
次要结局
- 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)
- Functional Improvements (30-s chair stand)(Through study completion, an average of 1 year)
- rs-fcMRI as a biomarker of treatment response(Baseline, 12 weeks post-treatment)