Freet Christopher S, Shuler Kirsten, Kawasaki Sarah, Weintraub Eric, Greenblatt Aaron, Kladney Mat, Nunes Edward, Foster Katrina L, Kong Lan, Raja-Khan Nazia, Cleveland H Harrington, Grigson Patricia S, Bunce Scott C, Brick Timothy R, Nyland Jennifer E
Penn State College of Medicine.
University of Maryland School of Medicine.
Res Sq. 2025 May 26:rs.3.rs-6666196. doi: 10.21203/rs.3.rs-6666196/v1.
Standard medications for opioid used disorder (MOUD) provide effective treatment pathways for recovery compared with no treatment or behavioral therapies alone. That said, treatment-refractory opioid used disorder (OUD) often can limit effectiveness and contribute to high attrition and relapse rates. Novel, more effective approaches are needed for the treatment of OUD. To that end, glucagon-like peptide 1 receptor agonists (GLP-1RAs) provide a promising option as a non-opioid pharmacological intervention for OUD. Current data suggest that GLP-1RAs decrease craving measures in a residential OUD population but, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can increase abstinence for substance use and reduce craving in individuals with OUD in an outpatient population. The purpose of the current protocol is to evaluate the potential for the GLP-1RA, semaglutide, to effectively increase abstinence and reduce craving in an outpatient population enrolled in a MOUD program and experiencing treatment refractory OUD.
This protocol is a randomized, double-blind, placebo-controlled clinical trial designed to test the efficacy of the GLP-1RA, semaglutide, in 200 participants enrolled in an outpatient MOUD program (n = 100 buprenorphine; n = 100 methadone) for the treatment of OUD. Outcomes include the probability of participants being abstinent from illicit and nonprescribed opioids, as well as measures of craving and days of drug use. Measures will be evaluated using urine toxicology screens and self-report assessments across 19 weeks during a screening visit (Study Week 1), 12 treatment visits (Study Weeks 2-13), a washout visit (Study Week 14), and a final follow-up visit (Study Week 19).
This manuscript describes a phase II clinical protocol to collect data on the efficacy of a GLP-1RA, semaglutide, in persons enrolled in a MOUD program and experiencing treatment-refractory OUD. Completion of the current project will support the feasibility of phase III clinical trials for further evaluation in larger outpatient OUD populations that may lead to a new indication for GLP-1RA as a novel and effective treatment for OUD.
ClinicalTrials.gov: NCT06548490. Registered 12 August 2024, https://clinicaltrials.gov/study/NCT06548490.
与不治疗或仅采用行为疗法相比，用于阿片类物质使用障碍（MOUD）的标准药物为康复提供了有效的治疗途径。话虽如此，难治性阿片类物质使用障碍（OUD）往往会限制疗效，并导致高脱落率和复发率。治疗OUD需要新的、更有效的方法。为此，胰高血糖素样肽1受体激动剂（GLP-1RAs）作为一种用于OUD的非阿片类药物干预措施，提供了一个有前景的选择。目前的数据表明，GLP-1RAs可降低住院OUD患者的渴求程度，但迄今为止，尚未进行对照临床试验来确定GLP-1RA是否能提高门诊OUD患者的物质使用戒断率并减少其渴求。本研究方案的目的是评估GLP-1RA司美格鲁肽在参加MOUD项目且患有难治性OUD的门诊患者中有效提高戒断率并减少渴求的潜力。
本研究方案是一项随机、双盲、安慰剂对照的临床试验，旨在测试GLP-1RA司美格鲁肽对200名参加门诊MOUD项目（n = 100名使用丁丙诺啡；n = 100名使用美沙酮）治疗OUD的参与者的疗效。结果包括参与者戒除非法和非处方阿片类物质的概率，以及渴求程度和药物使用天数的测量。将在筛查访视（研究第1周）、12次治疗访视（研究第2 - 13周）、洗脱期访视（研究第14周）和最终随访访视（研究第19周）的19周内，通过尿液毒理学筛查和自我报告评估来评估各项指标。
本手稿描述了一项II期临床研究方案，以收集关于GLP-1RA司美格鲁肽对参加MOUD项目且患有难治性OUD的患者疗效的数据。完成当前项目将支持III期临床试验对于更大规模门诊OUD患者群体进行进一步评估的可行性，这可能会为GLP-1RA作为一种治疗OUD的新型有效疗法带来新的适应症。
ClinicalTrials.gov：NCT06548490。于2024年8月12日注册，https://clinicaltrials.gov/study/NCT06548490 。
