Clinical Efficacy of Lisdexamfetamine for Methamphetamine Dependence

赖右苯丙胺治疗甲基苯丙胺依赖的临床疗效

• 批准号: 8581863
• 负责人: MICHAEL J MANCINO
• 金额: $ 18.44万
• 依托单位: UNIV OF ARKANSAS FOR MED SCIS
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-01 至 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8581863
• 关键词: Abstinence; Address; Adverse event; Agonist; Amphetamines; Appointments and Schedules; Area; Arkansas; Attention deficit hyperactivity disorder; Attenuated; Behavioral; Bulla; Childhood; Clinical; Clinical Trials; Cognitive Therapy; Controlled Clinical Trials; Data; Dependence; Development; Diagnosis; Disease; Dose; Double-Blind Method; Drug Addiction; Drug abuse; Economics; Electrocardiogram; Enzymes; Equilibrium; Exposure to; FDA approved; Future; Goals; HIV; Home environment; Hydrolysis; Incentives; Individual; Intervention; Intestines; Legal; Length; Light; Measures; Medical; Methamphetamine; Methamphetamine dependence; Methodology; Modeling; Monitor; Morbidity - disease rate; Neurotransmitters; Nicotine; Oral; Outcome; Outpatients; Participant; Patients; Pharmaceutical Preparations; Pharmacotherapy; Pilot Projects; Placebo Control; Placebos; Prevalence; Prodrugs; Psychostimulant dependence; Psychotherapy; Psychotic Disorders; Public Health; Randomized; Recovery; Relapse; Relative (related person); Research; Research Design; Research Project Grants; Residential Facilities; Risk; Safety; Sampling; Severities; Societies; Staging; Substance Use Disorder; Substance Withdrawal Syndrome; Testing; Therapeutic; Time; Toxic effect; Toxicology; Treatment outcome; Urine; Visit; Withdrawal; Withdrawal Symptom; base; clinical efficacy; clinical practice; cognitive function; contingency management; craving; drug abstinence; evidence base; follow-up; improved; in vivo; mortality; neurotoxic; novel; novel strategies; prevent; prognostic; programs; psychosocial; public health relevance; receptor; response; sex; social; treatment program; treatment response; volunteer

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.

描述（由申请人提供）：本申请是根据 PA-11-261 重新提交的，题为“探索性发展研究资助计划”。甲基苯丙胺 (METH) 依赖会带来严重的医疗、社会和社会后果。很少有研究探讨了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功效。药物开发也受到普遍采用检查戒断开始而不是预防复发的研究设计的阻碍。早期戒断通常与戒断症状和冰毒复发有关。一种有前途的治疗方法涉及使用间接激动剂药物治疗来治疗 METH 依赖；然而，研究很少，而且方法上有很大差异。尽管对包括兴奋剂尼古丁在内的其他药物依赖的激动剂治疗取得了成功，但由于多种原因，人们不愿意更仔细地检查对兴奋剂依赖的激动剂治疗，包括与长期接触安非他明相关的滥用、精神病和神经毒性作用的可能性。因此，考虑到利用短期激动剂疗法缓解戒断症状的潜力，本提案将检查激动剂赖右苯丙胺 (LDX) 在 1) 延迟复发时间和 2) 减轻最近戒断冰毒依赖个体的戒断症状方面的功效。这项为期 9 周、随机、双盲、安慰剂对照的临床试验将在两年内为 40 名冰毒依赖者（18-65 岁）个体提供治疗。参与者首先将居住在住宅设施（阿肯色州康复中心）以启动 最初戒毒并开始使用研究药物。他们将根据性别、依赖性严重程度和儿童 ADHD 诊断进行随机分组，接受安慰剂 (N=20) 或 LDX（100 毫克/天；N=20）。然后参与者转移到门诊治疗研究计划并继续接受第 2-4 周的研究药物治疗，并在第 5-6 周期间逐渐减少研究药物治疗。在试验的门诊部分，受试者每周参加一次个人认知行为治疗。在试验期间，参与者将因遵守研究要求而获得金钱奖励。 9 周结束时，患者将接受研究结束评估，并被转介至适当的治疗计划。确定长期疗效的最终评估将在研究完成后第 13 周或第 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通过尿液毒理学确定的复发/复发的时间长度。该试验的结果如果是积极的，将支持 R01 申请来检查 LDX 的功效以及较大样本中各种因素的预后相关性。因此，随着针对冰毒依赖的有效药物疗法的开发，这些发现可能会改变临床实践。