Administrative and Scientific Core

行政和科学核心

基本信息

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
项目类别：
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

项目摘要

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增强药物并使用遗传方法最佳地匹配成功的可卡因药物治疗作为二硫仑和加巴再摄取阻滞剂tiagabine to依赖可卡因患者的亚组。我们是进行了两项门诊随机临床试验和一系列新的实验室筛查研究 GABA增强剂。项目1是一项随机，安慰剂对照的，为期12周的临床试验，检查150 在二硫兰氏症和GABA再摄取阻滞剂试验中，可卡因依赖性美沙酮稳定的患者 tiagabine。这些患者将根据功能性多巴胺β羟化酶（DBH）进行分层。多态性仅在具有遗传的患者中预测对二硫兰氏的治疗反应导致DBH水平较低的单倍型和相对较高的多巴胺（DA）水平。项目2包括140 在一个随机的，安慰剂对照的，12周与四个治疗组的复发试验：安慰剂，舍曲林，舍曲林 + tiagabine和Sertraline + 加巴喷丁。该试验包括最初的2周住院禁欲。两个项目1和 2将对GABA相关的多态性进行基因筛查作为治疗的潜在预测指标在未来的研究中对GABA增强剂的反应。项目3将使用可卡因管理对人类的管理实验室为了筛选五个GABA增强剂，以作为药物疗法的潜在效用。这些三个项目涉及在临床试验和人类实验室。这些临床试验在Diasulfiram。或 GABA增强剂 - tiagabine和gabapentin的DA再摄取阻滞剂舍曲林与DA还原。总体而言，将在该中心研究300多名患者，并在两期门诊期间进行八个不同的药物试验或人类实验室研究。