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

随机双盲安慰剂对照试验：功能磁共振成像评估退伍军人纤维肌痛的颅脑电刺激

• 批准号: 10284922
• 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/10284922
• 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：伍德伯里博士是一个8/8 VA支付雇用双板认证麻醉师和疼痛 寻求受保护的时间来发展先进的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：视觉和视觉中心 Neurocognitive Research（CVNR）是VA RR&D卓越研究中心（COE），并提供 与附近的埃默里大学合作，拥有强大的临床研究环境。研究：在 在阿片类药物流行的背景下，开发疼痛的非药物治疗和生物标志物至关重要， 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- 在患有纤维肌痛的患者中治疗慢性疼痛的药理学方法（众所周知的困难 以治疗疼痛综合征），利用神经成像作为生物标志物。静息状态功能连接MRI（rs- fcMRI），一种特异性神经成像技术，已经成为一种可靠的研究工具， 了解并预测纤维肌痛等综合征的临床疼痛。CDA-1的初步结果 研究揭示了使用FDA批准非药物治疗的疼痛和功能改善的趋势 治疗-耳部经皮电神经场刺激（PENFS）-超过标准治疗控制， 与rs-fcMRI上改变的网络连接相关。与养恤金基金系统有关的改进持续到12 治疗完成后的几周内，并与跨网络连接的变化相关， 不同的群体之间。目的：拟议的CDA-2，一项随机、假对照试验， PENFS，评价1）与假安慰剂对照相比，PENFS治疗纤维肌痛的临床效用，2） rs-fcMRI上可见的短期和长期PENFS相关神经变化; 3）rs-fcMRI 预测PENFS治疗反应。假设：真正的PENFS导致非安慰剂相关的短期和 长期疼痛和功能改善，可能与连接改变相关，并通过 基线rs-fcMRI。方法：50名受试者（男性和女性退伍军人，年龄20-60岁）将 随机分配至假耳PENFS（n=25）或真耳PENFS（n=25）。神经影像学数据，自我报告的疼痛，以及 将在基线和治疗后1周和12周评估功能，以评价 PENFS相关治疗符合研究标准的受试者将接受基线评估，包括rs- fcMRI、国防和退伍军人疼痛评定量表（DVPRS）测量、PROMIS测量、手臂卷曲、30秒椅 站立、握力试验和基线镇痛药消耗量。受试者将接受区组随机化， 基于性别分层，分为真或假PENFS（4个系列，每周一次）治疗，并评估rs- 治疗后1周和12周的fcMRI和功能变化。这项研究解决了迫切需要， 识别和理解疼痛和非阿片类药物疼痛管理的神经相关性。职业生涯 发展方向：导师和合作者提供与神经解剖学相关的直接指导， 神经成像采集和分析，以及临床试验研究和数据分析。教学课程和 参加会议提供临床试验研究（完成临床研究理学硕士 课程）和先进的神经成像技能。从CDA-2培训中获得的经验和技能将 用于申请未来的建议，如VA Merit，以获得学术独立。近期目标： 1)以我从CDA-1中获得的知识为基础，使用神经成像作为生物标志物， 检查疼痛和镇痛效果的神经相关性，2）利用通过 我的MSCR和CDA-1培训进行随机，双盲，安慰剂对照临床试验。长- 目标：成为一名成功的研究者和疼痛研究的国际领导者，专注于1） 了解疼痛的神经相关性，2）开发更可靠和客观的慢性疼痛生物标志物 评估，和3）评估疼痛的非药物和阿片样物质保留疗法。