Randomized, placebo-controlled trial of injectable extended-release naltrexone and injectable extended-release buprenorphine for cocaine use disorder (CURB-2): Study rationale and design

IF 2 3区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Contemporary clinical trials Pub Date : 2025-05-11 DOI:10.1016/j.cct.2025.107954

Madhukar H. Trivedi , Mariah M. Kalmin , Thomas Carmody , Edward M. Chongsi , Udi E. Ghitza , Manish K. Jha , Taryn L. Mayes , Angela Casey-Willingham , Sangita Sethuram , Elise N. Marino , Maria Monastirsky , Steven J. Shoptaw

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引用次数: 0

Abstract

Background

Cocaine remains the most abused stimulant, causing considerable morbidity and mortality. Despite decades of research, there is no FDA-approved medication to treat cocaine use disorder (CUD). In individuals with cocaine and opioid dependence/abuse, extended-release injectable naltrexone (XR-NTX) and sublingual buprenorphine (BUP; 16 mg with naloxone; Suboxone) reduced cocaine use compared to placebo and XR-NTX in the ‘Cocaine Use Reduction with Buprenorphine’ (CURB; CTN-0048) study.

Objectives

The CURB-2 (CTN-0109) study aims to examine whether administering XR-NTX in combination with extended-release injectable buprenorphine (XR-BUP), thus creating a “kappa antagonist,” is an effective pharmacotherapy compared to placebo for the treatment of CUD.

Study design

CURB-2 is a fully powered, phase IIb, randomized, placebo-controlled trial. Approximately 426 participants will be randomized across 12 study sites in the United States. There will be a 1-week medication induction phase, an 8-week active medication phase, and a 4-week follow-up phase. XR-NTX (Day 1, Week 3, Week 6) will be administered before XR-BUP (Day 4, Week 4). With naltrexone blocking the mu-opioid receptors, the reinforcing effects of buprenorphine will be blocked while leaving the kappa antagonist effects.

Discussion

If this kappa antagonist approach demonstrates efficacy in reducing urine-verified cocaine use compared to placebo, XR-NTX and XR-BUP combination therapy would be an important tool in addressing cocaine use disorder.

Clinical Trials Registration: https://clinicaltrials.gov/ct2/show/NCT05262270.

查看原文本刊更多论文

注射用缓释纳曲酮和注射用缓释丁丙诺啡治疗可卡因使用障碍（CURB-2）的随机、安慰剂对照试验：研究原理和设计

可卡因仍然是滥用最多的兴奋剂，造成相当高的发病率和死亡率。尽管经过了几十年的研究，fda仍然没有批准治疗可卡因使用障碍（CUD）的药物。对于可卡因和阿片类药物依赖/滥用的个体，缓释注射纳曲酮（XR-NTX）和舌下丁丙诺啡(BUP；含纳洛酮16毫克；与安慰剂和XR-NTX相比，在“丁丙诺啡减少可卡因使用”(CURB；卡通- 0048)的研究。CURB-2 （CTN-0109）研究旨在检查XR-NTX与缓释注射丁丙诺啡（XR-BUP）联合使用，从而产生“卡帕拮抗剂”，与安慰剂相比，是否是治疗CUD的有效药物疗法。curb -2是一项全动力、IIb期、随机、安慰剂对照试验。大约426名参与者将被随机分配到美国的12个研究地点。将有1周的药物诱导期，8周的积极用药期和4周的随访期。XR-NTX（第1天，第3周，第6周）将在XR-BUP（第4天，第4周）之前给药。当纳曲酮阻断mu-阿片受体时，丁丙诺啡的强化作用将被阻断，同时留下kappa拮抗剂作用。如果与安慰剂相比，这种卡帕拮抗剂方法在减少尿检可卡因使用方面显示出疗效，XR-NTX和XR-BUP联合治疗将成为解决可卡因使用障碍的重要工具。临床试验注册：https://clinicaltrials.gov/ct2/show/NCT05262270。

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来源期刊

Contemporary clinical trials 医学-药学

CiteScore

3.70

自引率

4.50%

发文量

281

审稿时长

44 days

期刊介绍： Contemporary Clinical Trials is an international peer reviewed journal that publishes manuscripts pertaining to all aspects of clinical trials, including, but not limited to, design, conduct, analysis, regulation and ethics. Manuscripts submitted should appeal to a readership drawn from disciplines including medicine, biostatistics, epidemiology, computer science, management science, behavioural science, pharmaceutical science, and bioethics. Full-length papers and short communications not exceeding 1,500 words, as well as systemic reviews of clinical trials and methodologies will be published. Perspectives/commentaries on current issues and the impact of clinical trials on the practice of medicine and health policy are also welcome.