CDP-choline treatment in amphetamine type stimulant-using adolescents

 说明（由申请方提供）：近年来，苯丙胺类兴奋剂（ATS）使用的增加已成为一个主要的全球健康问题，ATS是指包括甲基苯丙胺（MA）和苯丙胺在内的一组兴奋剂。青少年中非医疗使用处方兴奋剂的比例很高，这一点也越来越令人关切。在这一竞争性更新的DA 024070，一个国际合作研究，旨在确定MA对发育中的大脑的影响，我们建议扩展我们的研究在ATS使用青少年，以评估一种新的治疗策略，为这一人群。 在初步研究结果的基础上，确定特定的大脑和认知的脆弱性，以刺激剂暴露和胞苷-5 '-二磷酸胆碱（CDP-胆碱）的神经保护特性，我们建议进行为期12周的，随机，双盲，安慰剂对照试验的CDP-胆碱在使用ATS的青少年。作为结局指标，将在分子、神经回路、认知和临床水平进行多水平评估。将确定与安慰剂施用相比，CDP-胆碱施用是否将1）修复目标脑区域内ATS诱导的神经细胞损伤，这将使用多核磁共振光谱成像来评估，2）改善认知缺陷并使相关目标神经回路正常化，这将使用神经心理学测试和多模态成像分析（包括皮质厚度分析）来评估，扩散张量成像分析和网络分析，以及3）减少ATS使用行为，这将使用尿液监测和ATS使用自我报告的组合进行评估。这项研究将证明CDP-胆碱参与治疗目标，从而为使用ATS的青少年提供临床益处。 在韩国首尔招募使用ATS的青少年等特殊人群的独特机会的背景下，该项目将在佩里F.美国犹他州犹他州大学脑研究所的Renshaw和Ewha脑研究所的In Kyoon Lyoo。韩国首尔大学。我们认为，这项研究提案是高度响应国际研究合作药物滥用和成瘾研究计划公告（PA-12- 040），鼓励利用独特的资源或受试人群，否则将难以获得国内。正如“2007年杰出国际科学家合作奖”和“2008年国际卓越计划奖[合作研究奖]”所承认的那样，我们建立的良好合作将有助于这项提案的成功。

 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.