Discontinuation From Chronic Opioid Therapy For Pain Using a Buprenorphine Taper

停止使用丁丙诺啡逐渐减量的慢性阿片类药物治疗疼痛

• 批准号: 9264513
• 负责人: Kelly S. Barth
• 金额: $ 20.08万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264513
• 关键词: Address; Aftercare; Agonist; Area; Buprenorphine; Characteristics; Chronic; Clinical; Cognitive Therapy; Dose; Double-Blind Method; Drug Metabolic Detoxication; Drug Prescriptions; Effectiveness; Epidemic; Fright; Future; Gender; Goals; Grant; Individual; Intervention; Investigation; Knowledge; Measures; Medical; Methods; Mission; N-Type Calcium Channels; National Institute of Drug Abuse; Opiate Addiction; Opioid; Opioid Analgesics; Outcome; Outcome Measure; Outpatients; Overdose; Pain; Pain management; Patient-Focused Outcomes; Patients; Phase; Phenotype; Placebo Control; Placebos; Population; Populations at Risk; Preventive Intervention; Protocols documentation; Randomized; Randomized Controlled Trials; Reporting; Research; Research Personnel; Risk; Risk Reduction; Role; Series; Standardization; Supervision; Testing; Treatment outcome; United States; Withdrawal; Withdrawal Symptom; addiction; base; career development; channel blockers; chronic pain; comparative efficacy; design; follow-up; functional outcomes; gabapentin; high risk population; improved; improved outcome; innovation; mortality; mu opioid receptors; multidisciplinary; opioid use; opioid use disorder; opioid withdrawal; overdose death; pain symptom; prescription opioid; prescription opioid misuse; primary outcome; programs; public health relevance; willingness

 DESCRIPTION (provided by applicant): A significant proportion of patients maintained on chronic opioid therapy for pain (COT-P) have suboptimal pain relief and/or poor functioning despite the appreciable risk of opioid treatment, including overdose death. There is a major gap in clinical knowledge regarding how to manage individuals on COT-P, especially those in need of opioid cessation. When an indication exists for discontinuation from COT-P, there is no empirical evidence as to how to approach opioid discontinuation or outcomes after opioid cessation. The long-term goal of this application is to expand the current knowledge about opioid discontinuation for those on COT-P. Buprenorphine, a partial mu-opioid receptor agonist, is well-suited for use in opioid tapering/detoxification settings, but there is a great need to evaluate the tolerability and effectiveness of buprenorphine for those on COT-P. Preliminary evidence suggests that buprenorphine induction is well-tolerated for those on COT-P, but tapering is challenging due to pain and withdrawal symptoms. The objectives of this application are to evaluate buprenorphine-assisted discontinuation from COT-P and to determine the role of gabapentin, an N-type calcium channel blocker, as an adjunctive agent to assist with opioid cessation. The central hypothesis of this study is that COT-P patients undergoing a buprenorphine taper with adjunctive gabapentin will have higher rates of opioid cessation when compared with those on buprenorphine/ placebo. Secondary hypotheses are that patients will have decreased pain after buprenorphine initiation and that those on adjunctive gabapentin will have lower withdrawal and pain scores when compared with placebo. To test these hypotheses, a two-phase study of buprenorphine-assisted opioid discontinuation will be conducted in 150 COT-P patients with an indication for opioid cessation. The specific aims of this study are: (1) To determine the base rate of buprenorphine tolerability among COT-P subjects, and (2) To examine the efficacy of gabapentin in improving outcomes during a buprenorphine-assisted taper from COT-P. The primary outcome measures will be buprenorphine tolerance and opioid cessation. The rationale for the proposed research is to determine base rates and effect sizes to inform a larger randomized- controlled trial of the effects of gabapentin on opioid cessation during buprenorphine-assisted taper from COT-P. It is expected that a significant number subjects will tolerate buprenorphine, and that those randomized to gabapentin will have higher rates of opioid cessation when compared with placebo. Additionally, it is hypothesized that there will be significant differences in pre- to post- induction and taper levels of pain associated with opioid cessation. Resumption of opioid analgesic use at 1-, 3- and 6-months post-taper will be measured. Such results are expected to have a positive impact by identifying approaches to facilitate opioid cessation when indicated, thereby decreasing risk for prescription opioid overdose. This innovative study will be the first to systematically explore both buprenorphine and gabapentin during opioid tapering in COT-P patients who do not have addiction and the first to systematically evaluate pain before and after opioid discontinuation.

 描述（由适用提供）：尽管有明显的阿片类药物治疗风险，包括过量的死亡，但在慢性阿片类药物治疗（COT-P）中维持的患者中有很大比例的疼痛缓解和/或功能不佳。关于如何在COT-P上管理个体，尤其是需要阿片类药物暂停的人，临床知识存在一个主要差距。当存在终止COT-P的迹象时，就没有关于如何处理阿片类药物停止后如何处理阿片类药物的经验证据。该应用程序的长期目标是扩大有关COT-P上的阿片类药物停用的当前知识。丁丙诺啡是一种部分MU阿片类药物接收器激动剂，非常适合用于阿片类药物锥形/排毒设置，但非常需要评估丁丙诺啡对COT-P上的丁丙诺啡的耐受性和有效性。丁丙诺啡诱导对COT-P的诱导症具有良好的耐受性，但是由于疼痛和戒断症状，​​逐渐减少了。该应用程序的目标是评估COT-P中丁丙诺啡辅助的停用，并确定Gabapentin（N型钙通道阻滞剂）作为协助阿片类药物戒烟的辅助药物的作用。这项研究的中心假设是，与丁丙诺啡/安慰剂相比，接受辅助加巴喷丁的COT-P患者接受丁丙诺啡锥度的锥形锥度将具有更高的阿片类药物戒烟率。次要假设是，丁丙诺啡倡议​​后患者的疼痛会减轻，与安慰剂相比，辅助加巴喷丁的患者的戒断和疼痛评分较低。为了检验这些假设，将在150名COT-P患者中进行丁丙诺啡辅助阿片类药物停止的两阶段研究。这项研究的具体目的是：（1）确定COT-P受试者之间丁丙诺啡耐受性的基本速率，以及（2）检查加巴喷丁在改善COT-P中丁丙诺啡辅助锥度期间结果的有效性。主要结果指标将是丁丙诺啡耐受性和阿片类药物戒烟。拟议的研究的基本原理是确定基本速率和效果大小，以告知加巴喷丁对丁丙诺啡辅助锥度在COT-P中的阿片类药物戒烟影响的较大随机对照试验。可以预期，与安慰剂相比，大量受试者将忍受丁丙诺啡，并且那些随机与加巴喷丁的人的阿片类药物停止率更高。另外，假设在诱导前与疼痛水平与相关的疼痛水平会有显着差异 Ooid停止。将测量在1个，3个月和6个月后恢复Ooid镇痛作用。预计通过识别指示时促进OID停止的方法，预计将产生积极的影响，从而降低处方OID过量的风险。这项创新的研究将是第一个在没有成瘾的COT-P患者中系统地探索丁丙诺啡和加巴喷丁的一项，并且在阿片类药物中断之前和之后首先要系统地评估疼痛。