Sequential Trial of Adding Buprenorphine, Cognitive Behavioral Treatment, and Transcranial Magnetic Stimulation to Improve Outcomes of Long-Term Opioid Therapy for Chronic Pain (ACTION)

添加丁丙诺啡、认知行为治疗和经颅磁刺激以改善长期阿片类药物治疗慢性疼痛的效果的序贯试验 (ACTION)

• 批准号: 10717184
• 负责人: Kelly S. Barth
• 金额: $ 329.06万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10717184
• 关键词: Acceleration; Address; Area; Benefits and Risks; Blinded; Brain; Buprenorphine; Caring; Cephalic; Clinical; Clinical Treatment; Cognitive Therapy; Data; Dose; Double-Blind Method; Ecological momentary assessment; Effectiveness; Enrollment; Ensure; Evaluation; Evidence based treatment; Fright; Harm Reduction; Helping to End Addiction Long-term; Impaired cognition; Individual; Intervention; Interview; Left; Measures; Mental Depression; Mission; National Institute of Drug Abuse; Opioid; Outpatients; Pain; Pain management; Patient Care; Patient-Centered Care; Patients; Persons; Phase; Placebos; Prefrontal Cortex; Process; Prospective cohort; Protocols documentation; Provider; Quality of life; Randomized; Readiness; Research; Research Design; Research Priority; Risk; Risk Reduction; Running; Safety; Science; Selection for Treatments; Severities; Standardization; Transcranial magnetic stimulation; United States National Institutes of Health; Weight; Withdrawal; Withdrawal Symptom; chronic pain; chronic pain management; clinical care; clinical outcome measures; clinical practice; cognitive enhancement; comparative effectiveness; design; discontinuation trial; double-blind placebo controlled trial; effective therapy; effectiveness evaluation; efficacy evaluation; empowerment; evidence base; experience; follow-up; improved; improved outcome; individualized medicine; innovation; insight; morphine equivalent; multidisciplinary; novel; novel therapeutic intervention; open label; opioid tapering; opioid therapy; opioid use; opioid withdrawal; optimal treatments; pain relief; patient engagement; patient oriented; prospective; repetitive transcranial magnetic stimulation; response; treatment planning; treatment trial

ABSTRACT A significant proportion of patients on Long Term Opioid Therapy (LTOT) have suboptimal pain relief and/or poor functioning despite significant risks. Because LTOT tapering can cause disabling withdrawal symptoms, the decision to taper or transition from LTOT can be daunting and create a clinical dilemma. Novel and effective treatment approaches that improve pain and quality of life (QOL) for individuals on LTOT while reducing risk are needed, but it is essential to ensure these initiatives are patient-centered. Offering treatment trials that can be “added to” current LTOT management without having to prospectively commit to an opioid taper or experience opioid withdrawal could significantly enhance the rates of safe, patient-centered, and effective LTOT risk reduction while improving pain and QOL. The proposed study addresses this critical need by sequentially evaluating trials of three evidence-based treatments for chronic pain that can be “added to” LTOT without having to experience opioid withdrawal or commit to a taper. In this study, individuals on LTOT will first trial a 7-day initiation of low-dose transdermal buprenorphine to determine safety and tolerability, and then will enter a blinded randomized discontinuation trial to evaluate efficacy of transdermal buprenorphine on pain severity among those on LTOT. Those who respond positively to the buprenorphine trial and want to transition to buprenorphine (and off LTOT) will be transitioned and followed as a prospective cohort. Those who do not respond to buprenorphine will undergo a second randomization evaluating the effectiveness of a Brief Cognitive Behavioral Intervention (CBI) for Pain combined with a 3-day “accelerated” course of Brain Stimulation (repetitive Transcranial Stimulation; rTMS) on pain severity. The proposed study aims to improve engagement of individuals on LTOT to make informed treatment decisions about LTOT; provide much needed safety and tolerability data on low-dose buprenorphine induction strategies; and evaluate the effectiveness of a novel combined non-pharmacological treatment that can address pain, opioid risk, and depression among those who do not respond to buprenorphine transition. Key innovations include the use of low-commitment, patient-centered ”trials” of treatment without mandating withdrawal and the evaluation of shorter “accelerated” protocols of brain stimulation that can enhance CBI that make this novel intervention scalable, generalizable and sustainable. This application is directly responsive to the FOA (RFA-DA-23-041), which underscores the importance of engaging individuals with lived experience to inform multilevel interventions aimed at improving quality of life and reducing harm for those on LTOT. It is also consistent with the research priorities of the HEAL initiative to optimize care for individuals with chronic pain and those at risk for opioid-related harms. The findings from this study will provide novel and critically needed empirical evidence to inform clinical practice and advance the science in this area.

抽象的 很大一部分接受长期阿片类药物治疗 (LTOT) 的患者疼痛缓解效果不佳和/或效果不佳 尽管存在重大风险，但仍能发挥作用，因为 LTOT 逐渐减少可能会导致失能的戒断症状， 逐渐减少或从 LTOT 过渡的决定可能会令人畏惧，并造成一种新颖且有效的临床困境。 可以改善 LTOT 患者的疼痛和生活质量 (QOL)，同时降低风险的治疗方法是 需要，但必须确保这些举措以患者为中心，提供可行的治疗试验。 “添加到”当前的 LTOT 管理中，无需前瞻性地承诺阿片类药物逐渐减量或经验 阿片类药物戒断可以显着提高安全、以患者为中心和有效的 LTOT 风险率 拟议的研究通过顺序解决了这一关键需求。 评估三种可“添加到”LTOT 的慢性疼痛循证疗法的试验 在本研究中，服用 LTOT 的个体无需经历阿片类药物戒断或逐渐减量。 将首先试验为期 7 天的低剂量透皮丁丙诺啡以确定安全性和耐受性，以及 然后将进入一项盲法随机停药试验，以评估透皮丁丙诺啡对 那些对丁丙诺啡试验有积极反应并想要接受 LTOT 的人的疼痛严重程度。 过渡到丁丙诺啡（以及停用 LTOT）的患者将作为前瞻性队列进行过渡和跟踪。 对丁丙诺啡没有反应将进行第二次随机分组，评估简报的有效性 针对疼痛的认知行为干预 (CBI) 结合为期 3 天的“加速”脑刺激课程 （重复经颅刺激；rTMS）对疼痛严重程度的影响拟议的研究旨在提高参与度。 接受 LTOT 的个人做出有关 LTOT 的明智治疗决定，提供急需的安全性和 低剂量丁丙诺啡诱导策略的耐受性数据并评估新型药物的有效性； 联合非药物治疗可以解决患者的疼痛、阿片类药物风险和抑郁症 对丁丙诺啡过渡没有反应关键创新包括使用低承诺、以患者为中心的药物。 不强制退出的治疗“试验”以及较短的大脑“加速”方案的评估 可以增强 CBI 的刺激，使这种新颖的干预措施具有可扩展性、可推广性和可持续性。 应用程序直接响应 FOA (RFA-DA-23-041)，这强调了参与的重要性 具有生活经验的个人可以为旨在提高生活质量和减少生活质量的多层次干预提供信息 这也符合 HEAL 计划优化护理的研究重点。 这项研究的结果将为患有慢性疼痛和有阿片类药物相关危害风险的人提供帮助。 新颖且急需的经验证据可为临床实践提供信息并推进该领域的科学发展。