Optimizing Pain Treatment while Reducing Abuse Liability in Opioid Dependence

优化疼痛治疗，同时减少阿片类药物依赖的滥用责任

基本信息

批准号：
8492049
负责人：
David Andrew Tompkins
金额：
$ 18.57万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-07-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8492049
关键词：
Absence of pain sensation Accident and Emergency department Acute Acute Pain Address Analgesics Area Attention Biological Factors Buprenorphine Chronic Clinical Clinical Pharmacology Clinical Trials Clinical Trials Design Clinical assessments Collection Complement Complex Conduct Clinical Trials Controlled Clinical Trials Data Disease Dose Double-Blind Method Drug Addiction Drug abuse Emotional Environmental Risk Factor Epidemic Evaluation Evaluation Methodology Exhibits Exposure to Funding Future Goals Grant Health Sciences Heating Histocompatibility Testing Hydromorphone Hyperalgesia Individual Individual Differences Intravenous Investigation Knowledge Lead Maintenance Measurement Measures Medical Mentored Patient-Oriented Research Career Development Award Mentors Methadone Modeling Musculoskeletal Pain Opiate Addiction Opioid Opioid Analgesics Outcome Pain Pain Measurement Pain Research Pain Threshold Pain management Pain-Free Participant Patient Self-Report Patients Persons Pharmaceutical Preparations Pharmacological Treatment Phase Placebo Control Placebos Population Preparation Procedures Process Property Provider Psychological Factors Recruitment Activity Research Research Personnel Risk Sensory Severities System Techniques Testing Training Training Programs Treatment outcome Visit Work addiction behavioral pharmacology career career development chronic pain cost design effective therapy experience nonmedical use patient oriented prescription opioid prescription opioid abuse pressure research study response substance abuse treatment

项目摘要

DESCRIPTION (provided by applicant): The abuse of prescription opioids has become a national epidemic, contributing to the enormous societal costs of drug addiction. Individuals repeatedly give pain as a leading reason underlying and maintaining this disorder, but there exists limited knowledge into how pain influences the risk for drug abuse. Although behavioral pharmacology experiments have validated the use of subjective and objective measurements of drug effects as clinically valuable predictors of abuse potential, few systematic investigations have comprehensively examined both the analgesic properties and abuse liability measurements in persons with opioid dependence after exposure to opioid analgesics. This application is for a K23 Mentored Patient-Oriented Research Career Development Award for Dr. David Andrew Tompkins to develop an independent research career in conducting clinical trials investigating effective strategies for the management of pain while reducing abuse liability in persons with opioid dependence. In his training plan, Dr. Tompkins proposes to expand his knowledge of clinical trial design, management, and analysis by concurrently pursuing a Master in Health Science degree in Clinical Investigation, participating in ongoing clinical trials of pharmacological treatment of addiction, and completing two new trials examining effective strategies for the management of acute pain in persons with opioid dependence. The new trials will allow Dr. Tompkins to gain expertise in quantitative sensory testing (QST) - a comprehensive evaluation methodology involving multiple experimental pain techniques that can assist researchers and clinicians in assessing both pain experiences and effective pain treatments. QST has rarely been used in opioid dependent populations but may ultimately provide a valid and reliable model for future pain research with these patients. Dr. Tompkins will utilize a double-blind placebo controlled design to measure the analgesic (change in experimental pain threshold and tolerance), subjective, and objective drug effects provided by intravenous doses of hydromorphone and buprenorphine in 3 groups: pain-free methadone maintained participants (N=30), pain-free buprenorphine maintained participants (N=30), and buprenorphine maintained participants with chronic musculoskeletal pain (N=30). Collection of QST and abuse liability data in these three separate populations will additionally allow for an investigation of the importance of maintenance agent and chronic musculoskeletal pain in the amount of drug required for significant increases in pain threshold and tolerance. Individual differences in analgesic response to QST will be examined, including use of the pain catastrophizing scale (PCS) - a scale that objectively measures important anticipatory and emotional aspects of pain. These two clinical trials will complement the training plan and aid in Dr. Tompkins' career development as an independent pain and addiction researcher and the results can be used in preparation of an R01 to (1) extend the work to larger Phase 2/3 controlled clinical trials of acute pain treatment, and/or (2) clinical trials to explore additiona analgesic medications or delivery systems.

描述（由申请人提供）：处方阿片类药物的滥用已成为全国范围内的流行病，造成了毒瘾的巨大社会成本。人们一再将疼痛视为导致和维持这种疾病的主要原因，但对于疼痛如何影响药物滥用风险的了解有限。尽管行为药理学实验已经验证了药物作用的主观和客观测量作为滥用潜力的临床有价值的预测因素，但很少有系统的研究全面检查阿片类药物依赖者暴露于阿片类镇痛药后的镇痛特性和滥用倾向测量。此申请旨在为 David Andrew Tompkins 博士申请 K23 指导患者导向研究职业发展奖，以开展独立研究职业，开展临床试验，研究疼痛管理的有效策略，同时减少阿片类药物依赖者的滥用倾向。在他的培训计划中，汤普金斯博士建议通过同时攻读临床研究健康科学硕士学位、参与正在进行的成瘾药物治疗临床试验以及完成两项新的临床试验设计、管理和分析知识来扩展他的临床试验设计、管理和分析知识。研究阿片类药物依赖者急性疼痛管理有效策略的试验。新的试验将使汤普金斯博士获得定量感觉测试（QST）方面的专业知识，这是一种涉及多种实验性疼痛技术的综合评估方法，可以帮助研究人员和临床医生评估疼痛体验和有效的疼痛治疗。 QST 很少用于阿片类药物依赖人群，但最终可能为这些患者的未来疼痛研究提供有效且可靠的模型。 Tompkins 博士将采用双盲安慰剂对照设计来测量 3 组静脉注射氢吗啡酮和丁丙诺啡所产生的镇痛（实验痛阈和耐受性的变化）、主观和客观药物效应：无痛美沙酮维持的参与者(N=30)、无痛丁丙诺啡维持参与者 (N=30) 和丁丙诺啡维持慢性肌肉骨骼疼痛参与者(N=30)。在这三个不同人群中收集 QST 和滥用倾向数据还将有助于调查维持剂和慢性肌肉骨骼疼痛在显着增加疼痛阈值和耐受性所需药物量方面的重要性。将检查 QST 镇痛反应的个体差异，包括使用疼痛灾难化量表 (PCS)——一种客观测量疼痛的重要预期和情绪方面的量表。这两项临床试验将补充培训计划，并帮助 Tompkins 博士作为独立疼痛和成瘾研究员的职业发展，其结果可用于准备 R01，以 (1) 将工作扩展到更大的 2/3 期控制急性疼痛治疗的临床试验，和/或 (2) 探索其他镇痛药物或输送系统的临床试验。