Varenicline for Methamphetamine Dependence

伐尼克兰治疗甲基苯丙胺依赖

基本信息

批准号：
8467805
负责人：
Steven J Shoptaw
金额：
$ 5.23万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-08-01 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8467805
关键词：
Abstinence Accounting Acetylcholinesterase Inhibitors Address Admission activity Adverse event Agonist Alcohol dependence Alcohols Behavior Therapy Binding Bupropion Cardiovascular Diseases Chemosensitization Cholinergic Agonists Cholinergic Receptors Cigarette Smoker Clinical Trials Design Cognitive Cognitive Therapy Corpus striatum structure County Data Development Dextroamphetamine Dose Double-Blind Method Drug Metabolic Detoxication Frequencies Funding Genes Genetic Polymorphism Glutamates HIV Infections Impaired cognition Individual Inpatients Lead Los Angeles Measurable Measurement Measures Mediating Methamphetamine Methamphetamine dependence Modafinil Naltrexone Neurobiology Nicotine Nicotinic Receptors Outcome Outpatients Participant Pharmaceutical Preparations Pharmacotherapy Phase I Clinical Trials Phase II Clinical Trials Placebo Control Placebos Population Preclinical Drug Evaluation Psychostimulant dependence Public Health Randomized Receptor Activation Relapse Research Personnel Safety Source Symptoms System Testing Time Treatment outcome United States Urine Withdrawal Withdrawal Symptom Withholding Treatment cannabinoid receptor cholinergic cigarette smoking contingency management craving design dopaminergic neuron effective therapy experience improved innovation novel pilot trial prevent psychological distress randomized placebo controlled trial receptor restoration smoking cessation treatment duration treatment response trend varenicline

项目摘要

DESCRIPTION (provided by applicant): Methamphetamine (MA) dependence is a significant source of deleterious consequences to individual and public health including HIV infection, psychological distress, and cardiovascular disease (Cruickshank and Dyer 2009), particularly in the Western United States. Behavioral treatments, including cognitive behavioral therapy (CBT) and contingency management (CM) are available (Lee and Rawson 2008) but are modestly effective. Medications that have efficacy in reducing MA use that could be integrated with behavioral therapies would represent a significant advancement in treatment. Cholinergic mechanisms are important in the neurobiology of stimulant dependence including MA (Hiranita, Nawata et al. 2008; Williams and Adinoff 2008). Varenicline is a 1422 nicotinic receptor partial agonist and 17 nicotinic receptor full agonist that is approved for cigarette smoking cessation (Gonzales, Rennard et al. 2006) and shows promise for treating alcohol dependence (McKee, Harrison et al. 2009). Varenicline may be effective for the treatment of MA dependence due to dopaminergic effects, relief of glutamatergic and cognitive dysfunction, and activation of nicotinic cholinergic systems. Building upon this rationale and preliminary experiences (in a Phase I clinical trial and a pilot Phase II trial), the investigators propose a randomized placebo-controlled, double-blind Phase II clinical trial of varenicline for MA dependence. Similar to smoking cessation treatment, study medication will be titrated to 1 mg BID over one week after which participants will take varenicline (1 mg BID) or placebo during a brief inpatient MA-detoxification period (4 nights) followed by 8 additional weeks of outpatient treatment with CBT. The brief inpatient detoxification is an important design innovation, as it facilitates all subjects to achieve a brief period of abstinence, to resolve initial withdrawal symptoms, and to allow measurement of varenicline efficacy as a MA withdrawal treatment. The subsequent 8-week outpatient treatment period allows the investigators to test varenicline for efficacy in preventing MA relapse during early abstinence. Although smoking cessation treatment is not provided, potential effects of varenicline on cigarette smoking will be assessed.

描述（由申请人提供）：甲基苯丙胺（MA）依赖是对个人和公共健康造成有害后果的一个重要来源，包括艾滋病毒感染、心理困扰和心血管疾病（Cruickshank 和 Dyer 2009），特别是在美国西部。行为治疗，包括认知行为治疗 (CBT) 和应急管理 (CM) 是可用的（Lee 和 Rawson 2008），但效果有限。能够有效减少 MA 使用并与行为疗法相结合的药物将代表治疗的重大进步。胆碱能机制在包括 MA 在内的兴奋剂依赖的神经生物学中非常重要（Hiranita、Nawata 等人，2008 年；Williams 和 Adinoff，2008 年）。 Varenicline 是一种 1422 烟碱受体部分激动剂和 17 烟碱受体完全激动剂，被批准用于戒烟（Gonzales, Rennard et al. 2006），并显示出治疗酒精依赖的前景（McKee, Harrison et al. 2009）。伐尼克兰可能因多巴胺能作用、缓解谷氨酸能和认知功能障碍以及激活烟碱胆碱能系统而有效治疗 MA 依赖。基于这一原理和初步经验（在 I 期临床试验和 II 期试验中），研究人员提出了一项伐尼克兰治疗 MA 依赖的随机安慰剂对照、双盲 II 期临床试验。与戒烟治疗类似，研究药物将在一周内滴定至 1 mg BID，之后参与者将在短暂的住院 MA 戒毒期（4 晚）期间服用伐尼克兰（1 mg BID）或安慰剂，然后再进行 8 周的门诊治疗CBT 治疗。短暂住院戒毒是一项重要的设计创新，因为它有助于所有受试者实现短暂的戒毒，解决最初的戒断症状，并允许测量伐尼克兰作为 MA 戒断治疗的疗效。随后的 8 周门诊治疗期使研究人员能够测试伐尼克兰在早期戒断期间预防 MA 复发的功效。尽管未提供戒烟治疗，但将评估伐尼克兰对吸烟的潜在影响。