Pilot Trial of Bupropion versus Placebo for Methamphetamine Abuse in Adolescents

安非他酮与安慰剂治疗青少年甲基苯丙胺滥用的试点试验

• 批准号: 7642248
• 负责人: Keith Gregory Heinzerling
• 金额: $ 16.2万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-15 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7642248
• 关键词: Address; Adolescent; Adult; Adverse event; Age; Attention deficit hyperactivity disorder; Auditory Hallucination; Behavior; Bupropion; Characteristics; Clinical; Clinical Trials; Clinical assessments; Complement; DNA; DNA Library; Data; Dependence; Deposition; Dose; Double-Blind Method; Drug Kinetics; Enrollment; Feeling suicidal; Frequencies; Future; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Methamphetamine; Methods; Monitor; Participant; Pharmaceutical Preparations; Pharmacogenomics; Pharmacotherapy; Phase II Clinical Trials; Pilot Projects; Placebos; Population; Prevalence; Procedures; Public Health; Randomized; Recording of previous events; Recruitment Activity; Reporting; Research; Respondent; Safety; Sampling; Severities; Specimen; Variant; Violence; aged; career; cigarette smoking; cognitive behavior therapy; contingency management; depressive symptoms; design; effective therapy; follow-up; genetic analysis; medication compliance; methamphetamine abuse; novel; peer; pilot trial; psychological distress; public health relevance; randomized placebo controlled trial; response; sex risk

DESCRIPTION (provided by applicant): Methamphetamine (MA) abuse among adolescents is a significant public health problem that is associated with psychological distress, depressive symptoms, auditory hallucinations, suicidal ideation, and high rates of violent behavior and HIV-related sexual risk behaviors. There are currently no effective medications for MA abuse available, although results from two preliminary randomized placebo-controlled trials of bupropion for MA dependent adults found bupropion to be more effective than placebo, but only among participants who reported low frequency MA use at baseline. Adolescent MA abusers are likely to have shorter MA use histories and therefore may respond to bupropion similarly to adults with baseline lower frequencies of MA use. As a result, bupropion represents an ideal candidate to evaluate as a pharmacotherapy for MA abuse among adolescents. Yet since no studies have examined pharmacotherapies for MA abuse among adolescents, a pilot study to assess the safety, tolerability, and acceptability of bupropion among adolescents with MA abuse and to optimize clinical trial methods for use with this population is needed before launching a full-scale clinical trial. Therefore we propose a pilot study to address the following specific aims: (1) To assess the feasibility of a randomized, double-blind clinical trial of bupropion versus placebo, in conjunction with cognitive behavioral therapy and contingency management targeting attendance, among adolescents with MA abuse, as assessed by rates of enrollment, compliance with study procedures including medication adherence, and retention. (2) To describe the safety and tolerability of bupropion compared to placebo among adolescents with MA abuse, as determined by the frequency and severity of adverse events for each condition. (3) To evaluate the utility of a novel recruitment method for recruiting adolescent MA abusers to the trial using a peer-referral strategy that is a variant of Respondent Driven Sampling. To achieve the objectives of this pilot study, we will enroll 30 adolescents (aged 14-21) seeking treatment for MA abuse who will be randomly assigned to receive treatment with bupropion extended release (XL) 300 mg once a day (n=20) or placebo once a day (n=10), in conjunction with cognitive behavioral therapy and contingency management targeting attendance, for 8 weeks followed by a 4 week follow-up period. The use of once daily dosing of bupropion XL is justified by pharmacokinetic studies in adolescents and may increase medication adherence. Participant safety, including possible suicidal ideation/behavior, will be monitored closely via a battery of clinical assessments throughout the trial. Additional exploratory efforts will provide formative data concerning the clinical characteristics of adolescents entering a MA medication clinical trial, including baseline frequency of MA use and prevalence of psychiatric disorders particularly ADHD, and will assess changes in ab libitum cigarette smoking during treatment. Results of the study are essential to designing a phase II clinical trial adequately powered to determine the efficacy of bupropion for MA abuse among adolescents. PUBLIC HEALTH RELEVANCE: Methamphetamine (MA) abuse among adolescents is a significant public health problem that is associated with psychological distress, depressive symptoms, auditory hallucinations, suicidal ideation, and high rates of violent behavior and HIV-related sexual risk behaviors. No studies have examined pharmacotherapies for MA abuse among adolescents, and therefore studies to identify effective pharmacotherapies for adolescents with MA abuse are urgently needed. The proposed pilot study has significant public health relevance in that it will provide critical data required for the design and implementation of a full scale clinical trial of bupropion, a medication that has shown efficacy for MA dependence in adults, for MA abuse in adolescents.

描述（由申请人提供）：青少年中的甲基苯丙胺（MA）滥用是一个重大的公共卫生问题，与心理困扰，抑郁症状，听觉幻觉，自杀式观念以及较高的暴力行为和与HIV相关的性风险行为有关。目前尚无对MA滥用的有效药物，尽管两项初步的随机安慰剂对照试验对MA依赖的成年人进行了安慰剂的试验，发现安单行比安慰剂更有效，但仅在报告基线低频MA使用的参与者中。青春期的滥用者可能会使MA使用历史较短，因此可能与基线较低频率MA使用的成年人相似。结果，安非他酮代表了作为青少年滥用MA的药物疗法评估的理想候选者。然而，由于没有研究检查青少年中的MA滥用药物治疗，因此一项试点研究，旨在评估滥用MA的青少年中安非他酮的安全性，耐受性和可接受性，并优化与该人群一起使用的临床试验方法，然后才能启动全面 - 比例临床试验。因此，我们提出了一项试点研究，以解决以下具体目的：（1）评估安慰剂与安慰剂的随机，双盲临床试验的可行性，以及认知行为疗法和应急管理的靶向出勤率，在MA根据入学率评估，遵守包括药物依从性和保留率在内的研究程序。 （2）描述与安慰剂在MA滥用的青少年中与安慰剂相比的安全性和耐受性，这取决于每种情况的不良事件的频率和严重性。 （3）评估一种新型招聘方法的实用性，以使用同行推荐策略招募青少年虐待者，该策略是受访者驱动的抽样的一种变体。为了实现这项试验研究的目标，我们将招募30名青少年（14-21岁）寻求MA滥用治疗的青少年，他们将被随机分配给Bupropion Extended Leasten（XL）300 mg每天300毫克（n = 20）或安慰剂每天一次（n = 10），与认知行为疗法和应急管理的靶向出勤，然后进行4周的随访期。在青少年中的药代动力学研究证明，每天使用安非他酮XL的每日使用，并可能增加药物依从性。参与者的安全，包括可能的自杀构想/行为，将通过整个试验中的一系列临床评估密切监视。额外的探索性工作将提供有关进入MA药物临床试验的青少年临床特征的形成性数据，包括MA使用的基线频率和精神疾病的患病率，尤其是ADHD，并将评估治疗过程中AB libitibum香烟吸烟的变化。该研究的结果对于设计了足够动力的II期临床试验至关重要，以确定安非他酮对青少年滥用的功效。公共卫生相关性：青少年中的甲基苯丙胺（MA）滥用是一个重大的公共卫生问题，与心理困扰，抑郁症状，听觉幻觉，自杀式观念以及较高的暴力行为率和与HIV相关的性风险行为相关。尚无研究检查青少年滥用MA的药物治疗，因此迫切需要为识别有效的MA滥用青少年的有效药物治疗的研究。拟议的试点研究具有很大的公共卫生相关性，因为它将为安非他酮的全面临床试验设计和实施所需的关键数据，该药物已显示出对成年人的MA依赖性的疗效，用于MA滥用青少年。