CDP-choline treatment in amphetamine type stimulant-using adolescents

 描述(申请人提供)：苯丙胺类兴奋剂(ATS)的使用增加，这是指包括甲基苯丙胺(MA)和苯丙胺在内的一组兴奋剂，近年来已成为一个主要的全球健康问题。青少年中非医疗使用处方兴奋剂的比例很高，这也越来越令人关切。在这项旨在确定MA对发育中大脑的影响的国际合作研究DA024070的竞争性更新中，我们建议扩展我们对ATS的研究-使用青少年来评估针对这一人群的新治疗策略。在初步研究结果的基础上，确定了青少年特有的大脑和认知对刺激剂暴露的脆弱性以及胞苷-5‘-二磷酸胆碱(CDP-胆碱)的神经保护特性，我们建议在使用ATS的青少年中进行一项为期12周的CDP-胆碱随机、双盲、安慰剂对照试验。作为结果衡量标准，将在分子、神经回路、认知和临床水平进行多水平评估。将确定与安慰剂注射相比，服用CDP-胆碱是否会1)修复ATS引起的靶脑区神经细胞损伤，这将使用多核磁共振光谱成像进行评估，2)改善认知缺陷和使相关靶神经电路正常化，这将通过神经心理测试和多模式成像分析(包括皮质厚度分析、扩散张量成像分析和网络分析)进行评估，以及3)减少服用ATS的行为，这将使用尿液监测和ATS使用自我报告进行评估。这项研究将证明CDP-胆碱与治疗目标相结合，从而为使用ATS的青少年提供临床益处。在韩国首尔招募特殊人群，如使用安非他明类兴奋剂的青少年这一独特机会的背景下，该项目将在美国犹他大学大脑研究所的Perry F.Renshaw和韩国首尔梨花大学Ehua Brain Institute的Kyoon Lyoo之间的国际合作的基础上实施。我们认为，这项研究建议是对国际药物滥用和成瘾研究合作研究计划公告(PA-12-040)的高度响应，该计划鼓励利用独特的资源或受试者群体，否则这些资源或受试者群体将难以在国内获得。正如在“2007杰出国际科学家合作奖”和“2008国际杰出项目奖[合作研究]”中所承认的那样，我们良好的合作将有助于这项计划的成功。

 DESCRIPTION (provided by applicant): The increased use of amphetamine-type stimulants (ATS), which refer to the group of stimulants including methamphetamine (MA) and amphetamine, has become a major global health problem in recent years. There is also an increasing concern about the high rate of the non-medical use of prescription stimulants among adolescents. In this competing renewal of DA024070, an international collaborative study aimed to determine the effects of MA on the developing brain, we propose to extend our studies in ATS-using adolescents to evaluate a novel treatment strategy for this population. On the basis of preliminary findings identifying adolescent-specific brain and cognitive vulnerability to stimulant exposure and the neuroprotective properties of cytidine-5'-diphosphate choline (CDP-choline), we propose to conduct a 12-week, randomized, double-blind, placebo-controlled trial of CDP-choline in ATS-using adolescents. As outcome measures, multi-level assessments will be performed at molecular, neural circuitry, cognitive, and clinical levels. It will be determined whether CDP-choline administration, compared to placebo administration, will 1) repair ATS-induced neural cell damage within the target brain regions, which will be assessed using multinuclear magnetic resonance spectroscopic imaging, 2) improve cognitive deficits and normalize the relevant target neural circuits, which will be assessed using neuropsychological tests and multimodal imaging analyses including cortical thickness analysis, diffusion tensor imaging analysis, and network analysis, and 3) reduce ATS-taking behaviors, which will be assessed using a combination of urine monitoring and self-report of ATS use. This study will demonstrate that CDP-choline engages the treatment target and thereby provides clinical benefits to ATS-using adolescents. In the context of the unique opportunity to recruit a special population, such as ATS-using adolescents, in Seoul, South Korea, this project will be performed based on the international collaboration between Perry F. Renshaw at the Brain Institute, the University of Utah, UT, USA and In Kyoon Lyoo at the Ewha Brain Institute, Ewha W. University, Seoul, South Korea. We believe that this research proposal is highly responsive to the International Research Collaboration on Drug Abuse and Addiction Research Program Announcement (PA-12- 040) that encourages the utilization of unique resources or subject populations which would otherwise be difficult to access domestically. As is also acknowledged in the '2007 Distinguished International Scientist Collaboration Award' and '2008 International Program Award for Excellence [Collaborative Research]', our well established collaboration will contribute to the success of this proposal.