A multisite, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine dependence.
A multisite, double-blind, placebo-controlled clinical trial to evaluate the safety and efficacy of vigabatrin for treating cocaine dependence.
复制标题
一项多中心、双盲、安慰剂对照临床试验，旨在评估氨己烯酸治疗可卡因依赖的安全性和有效性。
作者：
E. Somoza;D. Winship;C. Gorodetzky;D. Lewis;D. Ciraulo;G. Galloway;S. Segal;Michael Sheehan;J. Roache;W. Bickel;D. Jasinski;D. Watson;S. Miller;Peggy Somoza;T. Winhusen
重要性
可卡因依赖是一个重大的公共卫生问题，但目前还没有经过验证的药物治疗方法。此前在墨西哥进行的一项双盲单部位研究表明，有效的γ-氨基丁酸(GABA)能药Vigabatrin有效。
客观化
在美国样本中评估维卡百灵治疗可卡因依赖的安全性和有效性。
设计和设置
多地点、随机、双盲、安慰剂对照、为期12周的临床试验，在美国11个地点进行第13、16、20和24周的随访。
参与者
总共有186名寻求治疗的可卡因依赖者(平均年龄为45岁)。大约67%是男性，大约60%是非洲裔美国人。
干预措施
参与者接受了每天两次的Vigabatrin(总剂量，3.0g/d)或匹配的安慰剂，加上每周一次的计算机化认知行为治疗和为期13周的两周个体咨询。应急管理鼓励提供尿样。
主要成果和措施
主要的结果衡量标准是通过自我报告和定量尿液药物筛查评估参与者在12周治疗阶段的最后两周内戒除可卡因的比例。每周吸食可卡因的天数和1至13周期间无毒尿样的数量是关键的次要指标。
结果
在主要结果测量(P=.67)、关键辅助测量(P&gT；.99)或其他结果测量方面，Vigabatrin组和安慰剂组之间没有显著差异。然而，尽管药片计数和自我报告显示，超过66%的所有参与者(和Vigabatrin组的63%)服用了超过70%的药物，但服用Vigabatrin后的尿药浓度水平表明，大约40%到60%的服用Vigabatrin的患者可能没有得到遵守。这种缺乏依从性可能掩盖了万巴菊酯有效的任何证据。所有参与者均未出现视力或视野恶化的情况。
结论和相关性
对于任何结果变量，未检测到Vigabatrin治疗和安慰剂之间的疗效方案定义的差异。这可能是由于药物不依从性，或者是由于Vigabatrin的疗效较弱。
试行登记
ClinicalTrials.gov标识：NCT00611130。
IMPORTANCE
Cocaine dependence is a significant public health problem, yet no validated pharmacological treatment exists. The potent γ-aminobutyric acid (GABA)ergic medication vigabatrin has previously been shown to be effective in a double-blind single-site study conducted in Mexico.
OBJECTIVE
To evaluate the safety and efficacy of vigabatrin for the treatment of cocaine dependence in a U.S. sample.
DESIGN AND SETTING
Multisite, randomized, double-blind, placebo-controlled, 12-week clinical trial with follow-up visits at weeks 13, 16, 20, and 24 in 11 U.S. sites.
PARTICIPANTS
In total, 186 treatment-seeking participants with cocaine dependence (mean age, 45 years). Approximately 67% were male, and about 60% were of African American race/ethnicity.
INTERVENTIONS
Participants received twice-daily doses of vigabatrin (total dosage, 3.0 g/d) or matched placebo, plus weekly computerized cognitive behavioral therapy and biweekly individual counseling for 13 weeks. Contingency management encouraged the provision of urine samples.
MAIN OUTCOMES AND MEASURES
The primary outcome measure was the proportion of participants with cocaine abstinence during the last 2 weeks of the 12-week treatment phase as assessed by self-reports and quantitative urine drug screens. The weekly fraction of cocaine use days and the number of drug-free urine samples during weeks 1 through 13 were key secondary measures.
RESULTS
No significant differences were observed between the vigabatrin group and the placebo group on the primary outcome measure (P = .67), key secondary measures (P > .99), or other outcome measures. However, while pill counts and self-reports indicated that more than 66% of all participants (and >63% of the vigabatrin group) took more than 70% of their medication, post hoc vigabatrin urine concentration levels suggested that approximately 40% to 60% of patients taking vigabatrin may not have been adherent. This lack of adherence may have obscured any evidence of vigabatrin efficacy. No visual acuity or visual field deterioration occurred in any of the participants.
CONCLUSIONS AND RELEVANCE
No protocol-defined differences in efficacy between vigabatrin treatment and placebo were detected for any outcome variable. This may have been due to medication nonadherence or, alternatively, due to the weak efficacy of vigabatrin.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00611130.
γ-乙烯基 GABA 和可卡因的共同给药：临床前安全性评估。
影响因子：
6.1
作者：
Molina,PE;Ahmed,N;Ajmal,M;Dewey,S;Volkow,N;Fowler,J;Abumrad,N
通讯作者：
Abumrad,N
吸毒患者使用精神活性物质的时间线跟踪报告：心理测量特性。
影响因子：
5.9
作者：
Fals-Stewart,W;O'Farrell,TJ;Freitas,TT;McFarlin,SK;Rutigliano,P
通讯作者：
Rutigliano,P