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

项目总结 K23职业发展奖将使候选人成为一名独立的临床研究人员 具有完善和测试用于以下患者疼痛管理的药物行为干预的专业知识 密集康复。背景资料。疼痛是住院患者的一个重大问题，阿片类药物经常被使用 作为他们止痛治疗方法的一部分。不幸的是，足够的麻醉剂止痛伴随着 不良影响和上瘾风险。总体而言，全面住院康复患者的阿片类药物使用情况 (CIR)很高，因为他们的伤害很复杂。值得注意的是，康复中的疼痛会导致临床恶化。 结果，由于不适应的保健参与(例如，避免或过度使用物理治疗)。它是 对开发循证药物行为干预和调节开放标签安慰剂至关重要 (COLP)是一种在CIR中减少阿片类药物使用的有前景的技术。基于经典条件反射的原理， COLP利用阿片类药物药理学促进对安慰剂驱动的获得性反应 止痛药。明确的目标。建议的研究采用混合方法设计以：(1)在试点中进行评估 随机临床试验(RCT)，COLP治疗CIR疼痛患者的可行性和可接受性，(2)探索 与COLP相关的神经生理机制和标志物，以及(3)探讨组内纵向 疼痛管理的模式及其在多个时间点上的协变性。训练。候选人将会 通过资源丰富的制度环境和连贯的培训计划实现短期目标(1) CIR的临床试验设计，(2)神经生理学和信号分析及纵向数据收集，(3) 对疼痛管理的评估，包括对治疗的信念、期望和态度。此外 到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 有针对性的课程作业、授课培训和临床指导。在地方/国家会议上发表演讲，以及 在同行评议的期刊上发表，这些活动也包括在候选人的培训中。师徒关系。这个 候选人将得到一个优秀的指导团队的支持：Ross Zafonte，DO(主要导师)，Ted Kaptchuk (主要导师)Gloria Y.Yeh，医学博士，公共卫生硕士(联合导师)，Christine Sang，医学博士，公共卫生硕士(联合导师)，Kevin O‘Connor， 医学博士(顾问)和杰弗里·施奈德(顾问)。冲击力。根据NCMRR的资金优先顺序， 拟议的研究将回答以下关键问题：(1)多式联运的可行性和可接受性 对难以控制的症状进行药物行为干预的方法和(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的疼痛上， 预计应聘者的培训和研究将在各种医学领域得到广泛应用 与疼痛和麻醉剂治疗管理作斗争的人群。通过这个K23奖项，候选人 将获得申请更大规模的NCMRR临床试验(例如，R01或U01)所需的培训和初步数据 确定在接受强化康复治疗的患者中控制疼痛的COLP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.