Clinical Efficacy of Lisdexamfetamine for Methamphetamine Dependence

描述(由申请人提供)：本申请是对PA-11-261，题为“探索性发展研究资助计划”的重新提交。对甲基苯丙胺(冰毒)的依赖具有深远的医疗、社会和社会不良后果。很少有研究审查治疗这种疾病的潜在药物，包括缓解冰毒戒断症状的药物的疗效。药物开发也受到了阻碍，因为通常采用研究禁欲启动的研究设计，而不是防止复发。早期戒酒通常与戒断症状和复吸冰毒有关。一种有希望的治疗方法包括使用间接激动剂药物疗法治疗冰毒依赖；然而，研究很少，而且在方法学上有相当大的变异性。尽管激动剂治疗对包括兴奋剂尼古丁在内的其他药物的依赖取得了成功，但由于几个原因，人们一直不愿更密切地研究兴奋剂依赖的激动剂治疗，包括与长期接触苯丙胺相关的滥用、精神病和神经毒性效应的可能性。因此，考虑到利用短期激动剂疗法缓解戒断的可能性，这项建议将检验激动剂利塞非他明(LDX)在1)延迟复发时间和2)缓解最近戒断的冰毒依赖者的戒断症状方面的有效性。这项为期9周的随机、双盲、安慰剂对照临床试验将为40名冰毒依赖者(18-65岁)提供治疗。个人超过两年的时间。参与者首先将居住在一个住宅设施(阿肯色州恢复中心)，以启动 初始药物戒断，并对研究用药进行诱导。他们将根据性别、依赖的严重程度和儿童时期被诊断为ADHD的情况随机接受安慰剂(N=20)或LDX(100毫克/天；N=20)。然后，参与者转入门诊治疗研究计划，继续接受2-4周的研究药物治疗，并在5-6周逐渐减少研究药物治疗。在试验的门诊部分，受试者每周参加个人认知行为治疗。在试验期间，参与者将获得遵守研究要求的金钱奖励。在9周结束时，患者将接受研究结束评估，并被转介到适当的治疗计划。确定长期疗效的最终评估将在第13周，即研究完成后4周进行。疗效将取决于治疗时间的长短、戒断症状的缓解、认知功能的变化，以及尿毒学确定的失效/复发时间长短。这项试验的结果，如果是阳性的，将支持R01申请检查 大样本中LDX的疗效和各种因素与预后的相关性。因此，这些发现可能会改变临床实践，开发一种治疗冰毒依赖的有效药物疗法。

DESCRIPTION (provided by applicant): This application is a resubmission in response to PA-11-261, entitled "Exploratory Developmental Research Grant Program." Methamphetamine (METH) dependence has profound adverse medical, social and societal consequences. A paucity of studies has examined potential medications for treating this disorder, including the efficacy of medications to alleviate METH withdrawal symptoms. Medications development has also been hampered by generally employing study designs that examine the initiation of abstinence, rather preventing relapse. Early abstinence is often associated with withdrawal symptoms and relapse to METH use. A promising therapeutic approach involves the use of indirect agonist pharmacotherapy for METH dependence; however, studies are few and have considerable variability in methodology. Despite successful agonist treatments for dependence on other drugs, including the stimulant nicotine, there has been a reluctance to examine more closely agonist treatment for stimulant dependence for several reasons, including the potential for abuse, psychosis and neurotoxic effects associated with prolonged exposure to amphetamines. Thus, given the potential for alleviating withdrawal utilizing a short term agonist therapy, this proposal will examine the efficacy of the agonist Lisdexamfetamine (LDX) in 1) delaying time to relapse and 2) alleviating withdrawal symptoms in recently abstinent METH-dependent individuals. This 9-wk, randomized, double blind, placebo-controlled clinical trial will provide treatment for 40 METH-dependent (18-65 yrs.) individuals over a two-year period. Participants first will reside at a residential facility (Recovery Centers of Arkansas) to initiate initial drug abstinence and be inducted on the study medication. They will be randomized by sex, severity of dependence and childhood diagnosis of ADHD to receive either placebo (N=20) or LDX (100 mg/day; N=20). Then participants transfer to the Outpatient Treatment Research Program and continue to receive study medication for weeks 2-4 and be tapered off study medication during weeks 5-6. During the outpatient portion of the trial, subjects participate in weekly individual cognitive behavioral therapy. During the trial, participants are given monetary incentives for complying with study requirements. At the end of 9 weeks, patients will have end of study assessments and be referred to an appropriate treatment program. Final assessments to determine longer term efficacy will be obtained at week 13, 4 weeks after study completion. Efficacy will be determined by length of time in treatment, alleviation of withdrawal symptoms, changes in cognitive function, and length of time to lapse/relapse as determined by urine toxicology. The findings of this trial, if positive, will support an R01 application to examine the efficacy of LDX and prognostic relevance of various factors in a larger sample. As such, these findings may shift clinical practice with the development of an efficacious pharmacotherapy for METH dependence.