Medication Development Center for cocaine Use Disorder

可卡因使用障碍药物开发中心

• 批准号: 9729182
• 负责人: FREDERICK Gerard MOELLER
• 金额: $ 49.97万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9729182
• 关键词: Agonist; Brain; Clinical; Clinical Data; Clinical Trials; Cocaine; Cocaine Users; Data; Development; Disease; Dose; Drug Industry; Drug Interactions; FDA approved; Goals; Health; Human; Individual; Institution; Intervention; National Institute of Drug Abuse; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Population; Research; Research Methodology; Resources; Safety; Self Administration; Serotonin Receptor 5-HT2A; Training; Translational Research; United States Substance Abuse and Mental Health Services Administration; addiction; aged; base; brain research; cocaine use; cue reactivity; disorder later incidence prevention; dosage; industry partner; neuroimaging; novel; pre-clinical; preclinical study; receptor; response; tool; translational scientist

 DESCRIPTION (provided by applicant): This U54 Center will use translational research from brain to bedside as a tool for medication development in cocaine use disorder. Preclinical and early phase I clinical PK/PD data will provide information for go/no-go decisions on phase ll-lll clinical trials with medications that show promise for cocaine use disorder. The overall goal of this research is to create a center that can provide important preclinical and early phase I clinical data to NIDA and pharmaceutical industry partners on novel compounds for cocaine use disorder. The aims related to the theme of the center will be achieved through two cores and three projects: The Administrative Core (F. Gerard Moeller PI) serves as a general resource for the other Projects and the Educational Core, including oversight of fiscal and compliance matters, and will oversee interactions with outside entities including NIDA and the pharmaceutical industry. The Educational Core (William L. Dewey PI) will focus on training translational researchers for medication development for addictions across the two institutions. Project 1 (F. Gerard Moeller PI) is a Phase I human drug interaction study examining the safety of concurrent administration of cocaine with novel compounds, and the effects of the novel compounds on subjective response to cocaine and cocaine self-administration in non-treatment seeking CocUD subjects. The compounds to be studied will be the 5-HTac receptor agonist lorcaserin followed by the 5-HT2A receptor antagonist pimavanserin based on results of Project 3. Project 2 (Joel L. Steinberg PI) is a human neuroimaging study to determine the dose-related effects of the novel compounds (lorcaserin followed by pimavanserin) on brain function during cue reactivity tasks in abstinent CocUD subjects to provide further information on specific dosages and further evidence for go/no-go decisions on phase II clinical trials using medications as a tool to enhance relapse prevention. Project 3 (Kathryn C. Cunningham PI) is a preclinical study examining the effects of novel compounds (pimavanserin and pimavanserin plus lorcaserin) on self-administration and cue reactivity to fill in key information that is lacking on potential compounds for CocUD and will provide important information to support or refute phase I human studies.

 描述（由申请人提供）：该 U54 中​​心将使用从大脑到临床的转化研究作为可卡因使用障碍药物开发的工具。临床前和早期 I 期临床 PK/PD 数据将为继续/不继续决策提供信息。使用有望治疗可卡因使用障碍的药物进行 II-III 期临床试验 这项研究的总体目标是建立一个中心，为 NIDA 和制药行业合作伙伴提供有关新型化合物的重要临床前和早期 I 期临床数据。与该中心主题相关的目标将通过两个核心和三个项目来实现： 行政核心（F. Gerard Moeller PI）作为其他项目和教育核心的一般资源，包括监督。教育核心（William L. Dewey PI）将重点培训两个机构的成瘾药物开发转化研究人员。 （F. Gerard Moeller PI）是一项 I 期人类药物相互作用研究，检查安全性 可卡因与新化合物同时给药的效果，以及新化合物对寻求 CocUD 治疗的非治疗受试者对可卡因和可卡因自我给药的主观反应的影响。要研究的化合物将是 5-HTac 受体激动剂氯卡色林，其次是氯卡色林。 5-HT2A 受体拮抗剂 pimavanserin 基于项目 3 的结果。项目 2 (Joel L. Steinberg PI) 是一项人类神经影像研究，旨在确定新型化合物的剂量相关效应（氯卡色林，随后是匹莫范色林）对禁欲 CocUD 受试者提示反应任务期间的大脑功能进行研究，以提供有关特定剂量的更多信息以及使用药物作为加强预防复发预防的工具的 II 期临床试验的继续/不继续决策的进一步证据。 3（Kathryn C. Cunningham PI）是一项临床前研究，检查新型化合物（pimavanserin 和 pimavanserin 加 lorcaserin）对自我给药和提示反应性以填补缺少的关键信息 CocUD 的潜在化合物，并将为支持或反驳 I 期人体研究提供重要信息。

项目成果

Impulsivity and decision making in older and younger cocaine-dependent participants: A preliminary study.

老年和年轻可卡因依赖者的冲动和决策：一项初步研究。

• 发表时间: 2018
• 作者: Johns, Sade E;Wang, Qin;Straub, Lisa K;Moeller, F Gerard
• 通讯作者: Moeller, F Gerard

Laboratory impulsivity and depression in blast-exposed military personnel with post-concussion syndrome.

患有脑震荡后综合症的爆炸暴露军事人员的实验室冲动和抑郁。

• 发表时间: 2016-12-30
• 影响因子: 11.3
• 作者: Bjork, James M;Burroughs, Thomas K;Franke, Laura M;Pickett, Treven C;Johns, Sade E;Moeller, F Gerard;Walker, William C
• 通讯作者: Walker, William C

Suppression of cocaine relapse-like behaviors upon pimavanserin and lorcaserin co-administration.

匹马范色林和氯卡色林共同给药可抑制可卡因复发样行为。

• 发表时间: 2020
• 影响因子: 4.7
• 作者: Anastasio, Noelle C;Sholler, Dennis J;Fox, Robert G;Stutz, Sonja J;Merritt, Christina R;Bjork, James M;Moeller, F Gerard;Cunningham, Kathryn A
• 通讯作者: Cunningham, Kathryn A

Altered anterior cingulate cortex to hippocampus effective connectivity in response to drug cues in men with cocaine use disorder.

改变前扣带皮层与海马体的有效连接，以响应患有可卡因使用障碍的男性的药物提示。

• 发表时间: 2018-01-30
• 作者: Ma, Liangsuo;Steinberg, Joel L;Cunningham, Kathryn A;Bjork, James M;Lane, Scott D;Schmitz, Joy M;Burroughs, Thomas;Narayana, Ponnada A;Kosten, Thomas R;Bechara, Antoine;Moeller, F Gerard
• 通讯作者: Moeller, F Gerard

Cingulo-hippocampal effective connectivity positively correlates with drug-cue attentional bias in opioid use disorder.

阿片类药物使用障碍中扣带海马的有效连接与药物提示注意力偏差呈正相关。

• 发表时间: 2019
• 作者: Ma, Liangsuo;Steinberg, Joel L;Bjork, James M;Taylor, Brian A;Arias, Albert J;Terplan, Mishka;Anastasio, Noelle C;Zuniga, Edward A;Lennon, Michael;Cunningham, Kathryn A;Moeller, F Gerard
• 通讯作者: Moeller, F Gerard