Opioid Dose Reduction in Comprehensive Inpatient Rehabilitation: A pharmaco-behavioral approach

项目摘要 K23职业发展奖将使候选人成为独立的临床研究人员 具有完善和测试药物行为干预措施的专业知识， 强化康复。背景疼痛是住院患者的一个重要问题，经常使用阿片类药物 作为他们止痛治疗方法的一部分。不幸的是，通过麻醉剂充分缓解疼痛伴随着 不良影响和成瘾风险。总体而言，综合住院康复患者的阿片类药物使用情况 (CIR)是因为他们受伤的复杂性。值得注意的是，康复中的疼痛导致临床症状恶化。 结果，由于适应不良的医疗保健参与（例如，避免或过度使用物理治疗）。是 对开发循证药物行为干预至关重要，并调节开放标签安慰剂 （COLP）是减少CIR中阿片类药物使用的一种有前途的技术。基于经典条件反射的原理， COLP利用阿片类药物药理学促进诱发安慰剂驱动的学习反应 analgesia.具体目标。建议的研究采用混合方法设计：（1）在试点中评估， 随机临床试验（RCT），COLP用于CIR疼痛患者的可行性和可接受性，（2）探讨 与COLP相关的神经生理机制和标志物，以及（3）探索组内纵向 疼痛管理模式及其在多个时间点的协方差。训练候选人将 通过资源丰富的机构环境和连贯的培训计划实现短期目标（1） CIR中的临床试验设计，（2）神经生理学和信号分析以及纵向数据收集，以及（3） 疼痛管理的评估，包括;信念，期望和对治疗的态度。此外 参加正在进行的导师会议和通过研究计划进行的体验式培训，候选人将完成 有针对性的课程、教学培训和临床跟踪。在地方/国家会议上发言， 在同行评审的期刊上发表文章，这些活动也包括在候选人的培训中。导师制。的 候选人将得到一个一流的指导团队的支持：罗斯Zafonte，DO（主要导师），特德Kaptchuk （primary mentor）（主要导师）格洛丽亚Y. Yeh，医学博士，公共卫生硕士（共同导师），克莉丝汀桑，医学博士，公共卫生硕士（共同导师），凯文奥康纳， MD（顾问）和Jeffrey Schneider（顾问）。冲击根据NCMRR的供资优先事项， 建议的研究将回答关键问题（1）的可行性和可接受性的多式联运 涉及药物行为干预的方法，用于难以管理的症状和（2）制定目标 与实验干预相关的生物标志物。虽然最初的临床试验将集中在CIR的疼痛， 预计候选人的培训和研究将广泛应用于各种医学领域， 与疼痛和麻醉治疗管理作斗争的人群。通过K23奖，候选人 将获得申请更大的NCMRR临床试验所需的培训和初步数据（例如，R 01或U 01）至 确定COLP用于管理接受强化康复治疗的患者疼痛的最佳整合。

PROJECT SUMMARY This K23 career development award will position the candidate to become an independent clinical researcher with expertise in refining and testing pharmaco-behavioral interventions for pain management in patients under intensive rehabilitation. BACKGROUND. Pain is a significant problem for inpatients, and opioids are often used as a part of their analgesic treatment approach. Unfortunately, adequate pain relief by narcotic comes with adverse effects and risk of addiction. Overall, opioid usage for those in Comprehensive Inpatient Rehabilitation (CIR) is high due to the complexity of their injuries. Notably, pain in rehabilitation leads to worsened clinical outcomes, due to maladaptive healthcare engagement (e.g., avoidance or overuse of physical therapy). It is critical to developing evidence-based pharmaco-behavioral interventions, and Conditioning Open-Label Placebo (COLP) is a promising technique for reducing opioid use in CIR. Based on principles of classical conditioning, COLP takes advantage of opioids pharmacology to promote learned responses for evoked placebo-driven analgesia. SPECIFIC AIMS. The proposed studies employ mixed methods designs to: (1) evaluate, in a pilot randomized clinical trial (RCT), the feasibility and acceptability of COLP for patients with pain in CIR, (2) explore neurophysiological mechanisms and markers associated with COLP, and (3) explore within-group longitudinal patterns of pain management and their covariance across multiple timepoints. TRAINING. The candidate will achieve short-term goals through a resource-rich institutional environment and a cohesive training plan in (1) clinical trial design in CIR, (2) neurophysiology and signal analysis and longitudinal data collection, and (3) evaluation of pain management, including; beliefs, expectations, and attitudes toward the treatment. In addition to ongoing mentorship meetings and experiential training through the research plan, the candidate will complete targeted coursework, didactic training, and clinical shadowing. Presentations at local/national conferences, and publish in peer-reviewed journals, are activities also included in candidate’s training. MENTORSHIP. The candidate will be supported by a stellar mentoring team: Ross Zafonte, DO (primary mentor), Ted Kaptchuk (primary mentor) Gloria Y. Yeh, MD, MPH (co-mentor), Christine Sang, MD, MPH (co-mentor), Kevin O’Connor, MD (consultant), and Jeffrey Schneider (consultant). IMPACT. In line with NCMRR funding priorities, the proposed research will answer critical questions about (1) the feasibility and acceptability of a multimodal approach involving pharmaco-behavioral interventions for hard-to-manage symptoms and (2) develop objective biomarkers associated with the experimental intervention. While the initial clinical trial will focus on pain in CIR, it is anticipated that the candidate’s training and research will have broad applications to a variety of medical populations struggling with pain and narcotic treatment management. Through this K23 award, the candidate will gain the training and preliminary data needed to apply for a larger NCMRR clinical trial (e.g., R01 or U01) to determine the optimal integration of COLP for managing pain in patients undergoing intensive rehabilitation.