Trivedi Madhukar H, Kalmin Mariah M, Carmody Thomas, Chongsi Edward M, Ghitza Udi E, Jha Manish K, Mayes Taryn L, Casey-Willingham Angela, Sethuram Sangita, Marino Elise N, Monastirsky Maria, Shoptaw Steven J
Center for Depression Research and Clinical Care, Peter O'Donnell Jr. Brain Institute and Department of Psychiatry, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390, USA.
Department of Family Medicine, University of California, Los Angeles, 1800 Wilshire Blvd., Suite 1800, CA 90024, USA.
Contemp Clin Trials. 2025 Jul;154:107954. doi: 10.1016/j.cct.2025.107954. Epub 2025 May 11.
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.
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.
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.
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.
可卡因仍然是滥用最为严重的兴奋剂，会导致相当高的发病率和死亡率。尽管经过了数十年的研究，但尚无获得美国食品药品监督管理局（FDA）批准用于治疗可卡因使用障碍（CUD）的药物。在“丁丙诺啡减少可卡因使用”（CURB；CTN-0048）研究中，与安慰剂和长效注射用纳曲酮（XR-NTX）相比，对于同时存在可卡因和阿片类药物依赖/滥用的个体，长效注射用纳曲酮和舌下含服丁丙诺啡（丁丙诺啡16毫克与纳洛酮；舒倍生）可减少可卡因的使用。
CURB-2（CTN-0109）研究旨在探讨将XR-NTX与长效注射用丁丙诺啡（XR-BUP）联合使用，从而形成一种“κ拮抗剂”，与安慰剂相比，是否是一种治疗CUD的有效药物疗法。
CURB-2是一项具备充分效力的IIb期随机安慰剂对照试验。约426名参与者将在美国的12个研究地点进行随机分组。将有一个为期1周的药物诱导期、一个为期8周的活性药物期和一个为期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。由于纳曲酮会阻断μ阿片受体，丁丙诺啡的强化作用将被阻断，而κ拮抗剂作用则得以保留。
如果这种κ拮抗剂方法与安慰剂相比，在减少经尿液验证的可卡因使用方面显示出疗效，那么XR-NTX和XR-BUP联合疗法将成为解决可卡因使用障碍的一项重要工具。
