Administrative and Scientific Core

行政和科学核心

• 批准号: 7701058
• 负责人: THOMAS Richard KOSTEN
• 金额: $ 28.79万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7701058
• 关键词: Abstinence; Address; Agonist; Antidepressive Agents; Arkansas; Attenuated; Baclofen; Blood; Brain; Butyric Acid; Butyric Acids; Carrier Proteins; Chronic; Clinical Pharmacology; Clinical Trials; Cocaine; Cocaine Abuse; Collaborations; Connecticut; Consultations; Core Facility; Coupled; Data; Depressed mood; Development; Disease; Disulfiram; Dopamine; Dopamine Uptake Inhibitors; Dopamine-beta-monooxygenase; Drug usage; Electrophysiology (science); Enhancers; Functional Magnetic Resonance Imaging; Future; Generations; Genes; Genetic; Genetic Polymorphism; Genetic Screening; Glutamate Decarboxylase; Great Britain; Greece; Haplotypes; Human; Human Genetics; Individual; Inpatients; Interdisciplinary Study; International; Laboratories; Laboratory Study; Measures; Medicine; Mental Depression; Methadone; Methodology; Mexico; Mission; Molecular Genetics; Neurobiology; Neurosecretory Systems; New Agents; Norepinephrine; Numbers; Outcome; Outcome Assessment; Outpatients; Paranoia; Parkinson Disease; Patient Self-Report; Patients; Pennsylvania; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Phase II Clinical Trials; Phenotype; Placebo Control; Placebos; Procedures; Progesterone; Prolactin; Promoter Regions; Publications; Randomized; Randomized Clinical Trials; Range; Relapse; Relative (related person); Research; Research Personnel; Safety; Screening procedure; Series; Serotonin; Sertraline; Site; Spain; Specificity; Subgroup; Substance Addiction; Support of Research; Technology; Technology Transfer; Testing; Toxicology; Training; Transcranial magnetic stimulation; Transcriptional Activation; Universities; Up-Regulation; Urine; Virginia; Week; Withdrawal Symptom; Work; base; clinically significant; depressive symptoms; disorder later incidence prevention; drug abuse chemotherapy; endophenotype; enzyme activity; follow-up; gabapentin; genetic selection; improved; inhibitor/antagonist; innovation; interest; neuroimaging; neurotransmission; new technology; outcome forecast; poly(L-glutamic acid(60)-L-alanine(30)-L-tyrosine(10)); programs; promoter; receptor; response; reuptake; serotonin transporter; single photon emission computed tomography; tiagabine; topiramate; treatment program; valproate; week trial

This Center for Medications Development (MDU) has a theme of developing new GABA enhancing medications and using genetic approaches to optimally match successful cocaine pharmacotherapies such as disulfiram and the GABA reuptake blocker tiagabine to subgroups of cocaine dependent patients. We are conducting two outpatient randomized clinical trials and a series of five laboratory screening studies for new GABA enhancers. Project 1 is a randomized, placebo-controlled, 12-week clinical trial examining 150 cocaine-dependent methadone-stabilized patients in a trial of disulfiram and the GABA reuptake blocker tiagabine. These patients will be stratified based on a functional dopamine beta hydroxylase (DBH) polymorphism with the prediction of a treatment response to disulfiram only in those with the genetic haplotype that leads to low DBH levels and relatively higher dopamine (DA) levels. Project 2 includes 140 depressed, recently abstinent, cocaine-dependent patients in a randomized, placebo-controlled, 12-week relapse trial with four treatment groups: placebo, sertraline, sertraline + tiagabine and sertraline + gabapentin. This trial includes an initial 2 weeks of inpatient abstinence. The patients in both Projects 1 and 2 will undergo genetic screening of GABA related polymorphisms as potential predictors of treatment response to GABA enhancers in future studies. Project 3 will use cocaine administration to humans in a laboratory in order to screen five GABA enhancers for their potential utility as pharmacotherapies. These three projects involve examination of nine different potential cocaine pharmacotherapies in clinical trials and the human laboratory. These clinical trials offer an interesting contrast in DA enhancement by disulfiram .or the DA reuptake blocker sertraline versus DA reduction by the GABA enhancers - tiagabine and gabapentin. Overall, over 300 patients will be studied in this Center and eight different agents in either outpatient Phase II trials or human laboratory studies.

该药物开发中心（MDU）的主题是开发新的GABA增强剂。 药物和使用遗传方法，以最佳匹配成功的可卡因药物治疗， 作为双硫仑和GABA再摄取阻滞剂噻加宾，用于可卡因依赖患者亚组。我们 进行两项门诊随机临床试验和一系列五项实验室筛选研究， GABA增强剂。项目1是一项随机、安慰剂对照、为期12周的临床试验， 双硫仑和GABA再摄取阻滞剂试验中可卡因依赖性美沙酮稳定患者 噻加宾。这些患者将根据功能性多巴胺β羟化酶（DBH）进行分层 多态性与双硫仑治疗反应的预测，只有在那些与遗传 单倍型，导致低DBH水平和相对较高的多巴胺（DA）水平。项目2包括140个 抑郁症，最近戒断，可卡因依赖患者在一个随机的，安慰剂对照，12周 四个治疗组的复发试验：安慰剂、舍曲林、舍曲林+噻加宾和舍曲林+噻加宾 加巴喷丁本试验包括最初2周的住院禁欲。项目1和项目2中的患者 2例患者将接受GABA相关多态性的遗传筛查，作为治疗的潜在预测因子 在未来的研究中对GABA增强剂的反应。项目3将使用可卡因管理人类在一个 实验室，以筛选五种GABA增强剂作为药物治疗的潜在效用。这些 三个项目涉及在临床试验中检查九种不同的潜在可卡因药物疗法， 人类实验室这些临床试验提供了双硫仑增强DA的有趣对比。 DA再摄取阻滞剂舍曲林与GABA增强剂-噻加宾和加巴喷丁减少DA的对比。 总体而言，将在该中心研究300多名患者，并在门诊II期研究中使用8种不同的药物 试验或人体实验室研究。