Randomized Double-Blind Placebo-Controlled Trial: fMRI Assessment of Percutaneous Electrical Neural Field Stimulation for Fibromyalgia in Veterans

随机双盲安慰剂对照试验：经皮电神经场刺激治疗退伍军人纤维肌痛的功能磁共振成像评估

• 批准号: 10041711
• 负责人: Anna Woodbury
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-10-01 至 2024-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10041711
• 关键词: Acupuncture Therapy; Address; Affect; Aftercare; Age; American; Analgesics; Anxiety; Area; Autonomic nervous system; Award; Biological Markers; Brain; Brain region; Chronic; Clinical; Clinical Research; Clinical Trials; Complex; Consumption; Controlled Clinical Trials; Controlled Environment; Cranial Nerves; Data; Data Analyses; Dependence; Development; Development Plans; Devices; Diagnosis; Double-Blind Method; Ear; Educational Curriculum; Environment; External Ear; FDA approved; Feasibility Studies; Female; Fibromyalgia; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Future; Gender; Grant; Gulf War; Gulf War veteran; Human Resources; Incidence; International; Investigation; Knowledge; Lead; Learning; Long-Term Effects; Magnetic Resonance Imaging; Master of Science; Measurable; Measures; Mentors; Methods; Military Personnel; Moods; Nature; Nerve; Neuroanatomy; Neurocognitive; Neuronal Plasticity; Nonpharmacologic Therapy; Opioid; Outcome; Pain; Pain Measurement; Pain Research; Pain intensity; Pain management; Pain quality; Patient Self-Report; Patients; Placebo Control; Placebos; Prediction of Response to Therapy; Quality of life; Randomized; Registries; Research; Research Personnel; Rest; Rheumatology; Risk; Scientist; Series; Sleep; Sleeplessness; Symptoms; Synapses; Syndrome; System; Techniques; Testing; Time; Training; Treatment outcome; Universities; Variant; Veterans; Visual; Work; arm; base; career; career development; central pain; chronic pain; chronic painful condition; clinical biomarkers; clinical pain; clinical predictors; college; control trial; double-blind placebo controlled trial; experience; experimental study; feasibility trial; fibromyalgia pain; fibromyalgia patients; follow-up; functional improvement; global health; imaging approach; improved; male; neural correlate; neuroimaging; neuroimaging marker; neurophysiology; neurotransmission; non-opioid analgesic; novel; opioid epidemic; opioid sparing; opioid use; opioid withdrawal; pain outcome; pain processing; pain relief; predictive marker; primary outcome; relating to nervous system; responders and non-responders; secondary outcome; side effect; skills; symposium; tool; treatment effect; treatment response; trend

CANDIDATE: Dr. Woodbury is an 8/8 VA-paid employed double-board certified anesthesiologist and pain management clinician who seeks protected time to develop advanced neuroimaging and clinical trials expertise following successful completion of a CDA-1 feasibility study. ENVIRONMENT: The Center for Visual and Neurocognitive Research (CVNR) is a VA RR&D Center of Excellence (COE) in research and provides a robust clinical research environment in conjunction with nearby Emory University. 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, we 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 from our CDA-1 investigation reveal a trend towards improved pain and function with a FDA-approved, non-pharmacologic therapy - auricular percutaneous electrical neural field stimulation (PENFS) - over standard therapy control, correlating to altered network connectivity on rs-fcMRI. PENFS-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 PENFS, evaluates 1) the clinical utility of PENFS for fibromyalgia as compared to sham placebo control, 2) short- and long-term PENFS-related neural changes visualized on rs-fcMRI and 3) the ability of rs-fcMRI to predict PENFS treatment response. HYPOTHESIS: True PENFS 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 PENFS. 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 PENFS-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 PENFS (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. CAREER DEVELOPMENT PLAN: Mentors and collaborators provide direct guidance related to neuroanatomy, neuroimaging acquisition and analysis, and clinical trials research and data analysis. Didactic coursework and conference attendance provide clinical trials research (completion of Masters of Science in Clinical Research curriculum) and advanced neuroimaging skills. Experience and skills gained from the CDA-2 training will be used to apply for future proposals such as a VA Merit to gain academic independence. IMMEDIATE GOALS: 1) to build upon a foundation of knowledge gained from my CDA-1 in using neuroimaging as a biomarker to examine the neural correlates of pain and analgesic outcomes, and 2) to leverage the skills learned through my MSCR and CDA-1 training to conduct a randomized, double-blind, placebo-controlled clinical trial. LONG- TERM GOAL: to become a successful investigator and international leader in pain research, focusing on 1) understanding neural correlates of pain, 2) developing more reliable and objective biomarkers for chronic pain assessment, and 3) assessing non-pharmacologic and opioid-sparing therapies for pain.

候选人：伍德伯里医生是一名8/8退伍军人管理局受雇的双板认证麻醉师和疼痛医生 寻求有保障的时间来开发高级神经成像和临床试验专业知识的管理临床医生 在成功完成CDA-1可行性研究之后。环境：视觉和环境中心 神经认知研究(CVNR)是退伍军人管理局RR&D卓越研究中心(COE)，提供 强大的临床研究环境，与附近的埃默里大学合作。研究计划：在 在阿片类药物流行的背景下，至关重要的是开发疼痛的非药物治疗方法和生物标记物 准确评估疼痛治疗结果。在目前的调查中，我们评估了一种新的非 纤维肌痛患者慢性疼痛的药理学治疗(出了名的难 治疗疼痛综合症)，利用神经成像作为生物标记物。静息状态功能连接性磁共振(RS- FcMRI)是一种特定的神经成像技术，已成为客观评估 了解并预测纤维肌痛等综合征的临床疼痛。我们CDA-1的初步结果 研究显示FDA批准的非药物类药物有改善疼痛和功能的趋势 治疗-耳穴经皮电神经场刺激(PENFS)-超过标准治疗对照， 与RS-FcMRI上改变的网络连通性相关。与PENFS相关的改进持续到12年 在治疗完成后几周，并与跨网络连接的变化相关，这 不同群体之间的差异。目的：CDA-2是一项随机、假对照的耳穴治疗试验 评估了1)与假安慰剂对照相比，PENFS治疗纤维肌痛的临床效用，2) 在rS-fcMRI上显示的与PENFS相关的短期和长期神经变化和3)rS-fcMRI显示的 预测PENFS治疗反应。假设：真的PENFS会导致非安慰剂相关的短期和 长期疼痛和功能改善，可与连接性改变相关，并可通过 基线RS-fcMRI。方法：共50名受试者(男、女退伍军人，年龄20-60岁) 随机分为假耳穴(n=25)和真耳穴(n=25)。神经成像数据，自我报告的疼痛，以及 在基线以及治疗后1周和12周进行功能评估，以评估神经功能与 PENFS相关治疗。符合研究标准的受试者将接受基线评估，包括： 功能磁共振成像，国防和退伍军人疼痛评定量表，Promis测量，手臂卷曲，30-S椅 站立、握力测试和基线止痛药消耗量。受试者将被随机分组， 根据性别分层，进行真的或假的PENFS(4个系列，每周)治疗，并评估RS- 治疗后1周和12周的fcMRI和功能变化。这项研究解决了以下关键需求 识别和理解疼痛和非阿片类疼痛管理的神经关联。职业生涯 发展计划：导师和合作者提供与神经解剖学相关的直接指导， 神经影像采集和分析，临床试验研究和数据分析。授课课程和 出席会议提供临床试验研究(完成临床研究理学硕士学位 课程)和高级神经成像技能。从CDA-2培训中获得的经验和技能将是 用于申请未来的提案，如退伍军人奖励，以获得学术独立。近期目标： 1)以我从CDA-1获得的知识为基础，使用神经成像作为生物标记物 检查疼痛和止痛结果的神经相关性，以及2)利用通过 我的MSCR和CDA-1培训，以进行随机、双盲、安慰剂对照的临床试验。长- 任期目标：成为疼痛研究领域的成功研究者和国际领导者，专注于1) 了解疼痛的神经关联，2)开发更可靠和客观的慢性疼痛生物标志物 评估，以及3)评估非药物和非阿片类药物治疗疼痛。