Pharmacogenetic Trial of Noradrenergic Medication for Treatment of Cocaine Abuse

去甲肾上腺素能药物治疗可卡因滥用的药物遗传学试验

• 批准号: 8811837
• 负责人: Daryl I Shorter
• 金额: --
• 依托单位: MICHAEL E DEBAKEY VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8811837
• 关键词: Abstinence; Address; Adrenergic Agents; Adrenergic Antagonists; Affect; Alcohols; American; Angiotensin-Converting Enzyme Inhibitors; Animals; Anxiety; Anxiety Disorders; Bayesian Method; Behavior; Blood specimen; Clinical Treatment; Clinical Trials; Cocaine; Cocaine Abuse; Cocaine Dependence; Cognitive Therapy; Consent; Data; Data Analyses; Disease; Disulfiram; Doctor of Medicine; Doxazosin; Environment; Funding; Genes; Genetic; Genetic Polymorphism; Goals; Grant; Grant Review; Guanfacine; Health; Human; Individual; Institution; Learning; Location; Manuals; Measures; Medical; Medical center; Medicine; Mental disorders; Mentors; Neuropathogenesis; Outpatients; Participant; Patients; Persons; Pharmaceutical Preparations; Pharmacogenetics; Phase; Physician Executives; Placebos; Population Research; Post-Traumatic Stress Disorders; Preclinical Drug Evaluation; Preparation; Protocols documentation; Psyche structure; Psychiatrist; Psychiatry; Quality of life; Randomized; Research; Research Activity; Research Design; Research Personnel; Safety; Subgroup; Substance Use Disorder; System; Techniques; Texas; Time; Training; Treatment outcome; United States Food and Drug Administration; Urine; Veterans; addiction; adrenergic; anxiety symptoms; base; clinical practice; cocaine use; college; craving; design; double-blind placebo controlled trial; genetic analysis; improved; meetings; nepicastat; noradrenergic; novel; primary outcome; professor; programs; prospective; public health relevance; secondary outcome; skills; therapy development; week trial

DESCRIPTION (provided by applicant): Candidate Daryl Shorter, M.D. is a Staff Psychiatrist at Michael E. DeBakey VA Medical Center (MEDVAMC), Medical Director of the Outpatient Clinical Trials Research (OCTR) program, and Assistant Professor of Psychiatry at Baylor College of Medicine (BCM) who has served as co-investigator for studies addressing medication development for treatment of disorders such as cocaine dependence and PTSD. Dr. Shorter believes the quality of addictions treatment for veterans can be improved by evaluating novel medications for addictions treatment through clinical trials, and using pharmacogenetics to identify subpopulations of patients who will best respond to treatment. In the short-term, Dr. Shorter hopes to obtain mentored grant support through the VA CDA in order to (1) hone skills necessary to design and execute medication clinical trials for addictions and pharmacogenetics, and (2) generate pilot data to obtain independent funding. In the long-term, Dr. Shorter hopes to conduct prospective multisite trials for addictions treatment, employing pharmacogenetics, and bringing novel agents into clinical practice. Environment The research proposed in this CDA will take place in the OCTR program located at MEDVAMC. Directed by primary mentor, Thomas R. Kosten, M.D., the OCTR conducts medication trials for treatment of psychiatric and addictive disorders. Given the affiliation of OCTR with Menninger Department of Psychiatry and BCM, and its location in the Texas Medical Center, this environment offers an extensive network of academic and research institutions and study populations Research The educational objectives of the CDA will be met through completion of the outpatient, randomized double-blind, placebo controlled trial of doxazosin, an alpha-1 adrenergic antagonist, for treatment of cocaine addiction. This 17-week trial will randomize 150 participants onto either doxazosin 8mg/day or placebo; subjects will present to OCTR thrice weekly for urine drug screen and completion of research activities. All participants will receive manual-guided cognitive behavioral therapy. The a priori primary outcome is reduction in percentage of cocaine positive urines. Secondary outcomes include reduction in Hamilton Anxiety Rating Scale scores, retention, and safety/tolerability. Also, a blood sample will be collected from each participant consenting to genetic analysis. The training plan begins with management of the Doxazosin RCT and data analysis, first using a frequentist, and following with a Bayesian, statistical approach. During phase II, time spent in the genetics lab will provide learning of pharmacogenetics techniques; after which, genetic subgroup analysis using both frequentist and Bayesian approaches will be performed. During phases III and IV, adaptive research design skills will be learned, with preparation of a protocol comparing two compounds (doxazosin versus another medication) for cocaine treatment. This protocol will be used as the basis for a merit review grant.

描述（由申请人提供）： 候选人达里尔·肖特（Daryl Shorter），医学博士（M.D. Shorter博士认为，可以通过评估通过临床试验评估成瘾治疗的新型药物的成瘾治疗质量，并使用药物遗传学来确定最能对治疗反应的患者的亚群。在短期内，Shorter博士希望通过VA CDA获得指导的赠款支持，以（1）设计和执行成瘾和药物遗传学的药物临床试验所必需的唯一技能，以及（2）生成试验数据以获得独立资金。从长远来看，Shorter博士希望对成瘾治疗，采用药物遗传学，并将新颖的药物带入临床实践进行前瞻性多站点试验。 该CDA中提出的研究将在MEDVAMC的OCTR计划中进行。 OCTR由主要导师托马斯·R·科斯滕（Thomas R. Kosten）指导，OCTR进行了药物试验，以治疗精神病和成瘾性疾病。 Given the affiliation of OCTR with Menninger Department of Psychiatry and BCM, and its location in the Texas Medical Center, this environment offers an extensive network of academic and research institutions and study populations Research The educational objectives of the CDA will be met through completion of the outpatient, randomized double-blind, placebo controlled trial of doxazosin, an alpha-1 adrenergic antagonist, for treatment of cocaine addiction.这项为期17周的试验将将150名参与者随机添加到多克萨斯辛（Doxazosin）/天或安慰剂中；受试者将每周三次参加OCTR，以进行尿液药物筛查和完成研究活动。所有参与者将接受手动引导的认知行为疗法。先验的主要结果是可卡因阳性尿的百分比降低。次要结果包括降低汉密尔顿焦虑量评分评分，保留和安全性/耐受性。此外，将从每个参与者同意到遗传分析收集血液样本。培训计划始于多克萨斯素RCT和数据分析的管理，首先是使用常见主义者，然后采用贝叶斯统计方法。在第二阶段，在遗传学实验室中花费的时间将提供有关药物遗传学技术的学习。之后，将进行使用频繁主义和贝叶斯方法的遗传亚组分析。在第三阶段和IV阶段，将学习自适应研究设计技能，并准备一项协议，以比较两种化合物（多克萨斯辛与另一种药物）进行可卡因治疗。该协议将用作优异审查赠款的基础。