Martell Bridget A, Orson Frank M, Poling James, Mitchell Ellen, Rossen Roger D, Gardner Tracie, Kosten Thomas R
Department of Medicine, Yale University School of Medicine, New Haven, CT, USA.
Arch Gen Psychiatry. 2009 Oct;66(10):1116-23. doi: 10.1001/archgenpsychiatry.2009.128.
Cocaine dependence, which affects 2.5 million Americans annually, has no US Food and Drug Administration-approved pharmacotherapy.
To evaluate the immunogenicity, safety, and efficacy of a novel cocaine vaccine to treat cocaine dependence.
A 24-week, phase 2b, randomized, double-blind, placebo-controlled trial with efficacy assessed during weeks 8 to 20 and follow-up to week 24.
Cocaine- and opioid-dependent persons recruited from October 2003 to April 2005 from greater New Haven, Connecticut.
One hundred fifteen methadone-maintained subjects (67% male, 87% white, aged 18-46 years) were randomized to vaccine or placebo, and 94 subjects (82%) completed the trial. Most smoked crack cocaine along with using marijuana (18%), alcohol (10%), and nonprescription opioids (44%).
Over 12 weeks, 109 of 115 subjects received 5 vaccinations of placebo or succinylnorcocaine linked to recombinant cholera toxin B-subunit protein. Main Outcome Measure Semiquantitative urinary cocaine metabolite levels measured thrice weekly with a positive cutoff of 300 ng/mL.
The 21 vaccinated subjects (38%) who attained serum IgG anticocaine antibody levels of 43 microg/mL or higher (ie, high IgG level) had significantly more cocaine-free urine samples than those with levels less than 43 microg/mL (ie, low IgG level) and the placebo-receiving subjects during weeks 9 to 16 (45% vs 35% cocaine-free urine samples, respectively). The proportion of subjects having a 50% reduction in cocaine use was significantly greater in the subjects with a high IgG level than in subjects with a low IgG level (53% of subjects vs 23% of subjects, respectively) (P = .048). The most common adverse effects were injection site induration and tenderness. There were no treatment-related serious adverse events, withdrawals, or deaths.
Attaining high (>or=43 microg/mL) IgG anticocaine antibody levels was associated with significantly reduced cocaine use, but only 38% of the vaccinated subjects attained these IgG levels and they had only 2 months of adequate cocaine blockade. Thus, we need improved vaccines and boosters. Trial Registration clinicaltrials.gov Identifier: NCT00142857.
可卡因成瘾每年影响250万美国人，目前尚无美国食品药品监督管理局批准的药物疗法。
评估一种新型可卡因疫苗治疗可卡因成瘾的免疫原性、安全性和有效性。
一项为期24周的2b期随机双盲安慰剂对照试验，在第8至20周评估疗效，并随访至第24周。
2003年10月至2005年4月从康涅狄格州大纽黑文招募的可卡因和阿片类药物依赖者。
115名接受美沙酮维持治疗的受试者（67%为男性，87%为白人，年龄18 - 46岁）被随机分为疫苗组或安慰剂组，94名受试者（82%）完成了试验。大多数人吸食快克可卡因，同时使用大麻（18%）、酒精（10%）和非处方阿片类药物（44%）。
在12周内，115名受试者中的109名接受了5次安慰剂或与重组霍乱毒素B亚基蛋白结合的琥珀酰去甲可卡因疫苗接种。主要观察指标：每周三次测量半定量尿可卡因代谢物水平，阳性临界值为300 ng/mL。
21名接种疫苗的受试者（38%）血清IgG抗可卡因抗体水平达到43μg/mL或更高（即高IgG水平），在第9至16周期间，其可卡因阴性尿样显著多于抗体水平低于43μg/mL（即低IgG水平）的受试者和接受安慰剂的受试者（分别为45%和35%的可卡因阴性尿样）。高IgG水平受试者中可卡因使用量减少50%的比例显著高于低IgG水平受试者（分别为53%和23%）（P = 0.048）。最常见的不良反应是注射部位硬结和压痛。没有与治疗相关的严重不良事件、退出试验或死亡情况。
达到高（≥43μg/mL）IgG抗可卡因抗体水平与可卡因使用显著减少相关，但只有38%的接种疫苗受试者达到这些IgG水平，且他们仅有2个月的有效可卡因阻断期。因此，我们需要改进疫苗和加强剂。试验注册：clinicaltrials.gov标识符：NCT00142857。
