Personalized Treatment with Pharmacotherapy and CBT for Moderate Problem Drinking

药物治疗和 CBT 治疗中度饮酒问题的个性化治疗

• 批准号: 7990347
• 负责人: Andrew C. Chen
• 金额: $ 22.72万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-15 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7990347
• 关键词: Abstinence; Advocate; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohol or Other Drugs use; Alcoholism; Alcohols; Alleles; Award; Behavior Therapy; Behavioral; Behavioral Mechanisms; Candidate Disease Gene; Characteristics; Client; Clinical; Clinical Trials; Clinics and Hospitals; Cognitive; Cognitive Therapy; Complex; Conduct Clinical Trials; Data; Data Collection; Data Set; Dependence; Development; Disease; Doctor of Philosophy; Enrollment; Environmental Exposure; Family history of; Foundations; Frequencies; Funding; Future; GABA-A Receptor; General Population; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Variation; Genotype; Goals; Hand; Heavy Drinking; Heterogeneity; High Prevalence; Individual; Intervention; K-Series Research Career Programs; Link; Medication Management; Mental disorders; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Mind; Molecular; Moods; Motivation; Naltrexone; National Institute on Alcohol Abuse and Alcoholism; New York City; Opioid Receptor; Oral; Outcome; Outcome Measure; Parents; Pathology; Pathway interactions; Patient Self-Report; Patients; Pattern; Pharmaceutical Preparations; Pharmacogenetics; Pharmacotherapy; Pilot Projects; Placebos; Population; Population Research; Positioning Attribute; Promoter Regions; Psychiatrist; Psychiatry; Psychotherapy; Published Comment; Randomized; Receptor Gene; Recruitment Activity; Reporting; Research; Resources; Risk; Safety; Sampling; Self Efficacy; Self-control as a personality trait; Serotonin; Single Nucleotide Polymorphism; Social support; Stress; Stressful Event; Subgroup; Technology; Testing; Time; Training; Translational Research; Typology; Universities; Voice; Work; alcohol abstinence; alcohol related consequences; alcohol use disorder; base; career; cost; craving; cue reactivity; design; dosage; drinking; efficacy testing; experience; genetic variant; meetings; men who have sex with men; men' s group; mu opioid receptors; negative mood; novel; patient oriented research; patient population; problem drinker; psychosocial; public health relevance; receptor; response; safety study; serotonin transporter; skills; social; tool; topiramate; treatment response

DESCRIPTION (provided by applicant): Problematic alcohol drinking (the extreme form of which is alcohol dependence) is an etiologically and clinically heterogeneous phenomenon that is most likely caused by an interaction of genetic predisposition and environmental exposures. Recognition of this heterogeneity has led to a variety of attempts to develop multivariate, multi-dimensional typologies of alcohol dependence (AD). Several studies have shown that subgroups of alcoholics may respond differently to treatment with serotonergic medications and perhaps with naltrexone (NTX). The research component of this proposal is built upon on an on-going NIAAA-funded study on the efficacy of 12 weeks of randomly assigned treatment with NTX or cognitive behavioral therapy (CBT) or the two combined, in a population of problem-drinking men who have sex with men (MSM) in New York City and vicinity. The proposed K award will enable the candidate to study the genetic underpinnings of the individual treatment responses in this unique risk group whose social milieu and networks are more likely to involve the consumption of alcohol. Their disease manifestations are similar in many respects to those of the majority of hidden problem-drinkers in that they are generally high functioning and do not normally seek treatments that advocate complete abstinence as their goal. The objectives of the proposed study are to determine whether genetic variants in the genes encoding the serotonin transporter (5-HTTLPR), mu-opioid receptor (OPRM1), and GABA-A receptor subunit (GABRA2) are associated with the course and outcome of pharmacotherapy with naltrexone and/or cognitive behavioral psychotherapy treatment in this unique population. The candidate genes and polymorphisms were chosen based on recent studies showing small-to-moderate effects of these genetic variants on certain alcohol-related clinical characteristics. In addition to standard outcome measures, we propose to utilize a novel data collection technology, Interactive Voice Response, to collect data on daily relations among mood, craving, self-efficacy, motivation, and drinking. To augment the practicum in mastering the skills of design and implement of clinical trials for the candidate and to test the potential use of a new medication for moderation of drinking in a specific population, the research plan also includes a pilot study on the efficacy and safety of oral topiramate (200 mg/day) in the same high functioning MSM problem drinking group. Overall, the data generated from the studies and the methodology used will serve as a foundation for future studies of personalized treatments for AUD. This Mentored Patient-Oriented Research Career Award application will provide Andrew C. Chen, MD, PhD, a well trained psychiatrist and molecular neuroscientist, with the necessary time, mentorship and training to conduct high-quality clinical translational research, including pharmacogenetic approaches, to develop personalized treatments for alcohol use disorders (AUD). PUBLIC HEALTH RELEVANCE: Recent studies have shown that individuals with problematic alcohol drinking may respond to treatments differently. The proposed K award will enable the candidate to study the genetic underpinnings of the individual treatment responses. The data generated from the study and the methodology used will serve as a foundation for future development of personalized treatments of alcohol use disorders.

描述（由申请人提供）：有问题的饮酒（其极端形式是酒精依赖）是一种病因学和临床异质性现象，很可能是由遗传倾向和环境暴露的相互作用引起的。对这种异质性的认识导致人们尝试开发多变量、多维度的酒精依赖（AD）类型。几项研究表明，酗酒者的亚组可能对血清素药物以及纳曲酮 (NTX) 的治疗有不同的反应。该提案的研究部分建立在 NIAAA 资助的一项正在进行的研究的基础上，该研究的目的是在纽约市及周边地区的一群有问题的饮酒男性男男性行为者 (MSM) 人群中，随机分配 NTX 或认知行为疗法 (CBT) 或两者联合治疗 12 周的疗效。拟议的 K 奖将使候选人能够研究这一独特风险群体中个体治疗反应的遗传基础，这些群体的社会环境和网络更有可能涉及饮酒。他们的疾病表现在许多方面与大多数隐藏的酗酒者相似，因为他们通常功能良好，通常不会寻求以完全戒酒为目标的治疗。 本研究的目的是确定编码血清素转运蛋白 (5-HTTLPR)、μ-阿片受体 (OPRM1) 和 GABA-A 受体亚基 (GABRA2) 的基因中的遗传变异是否与这一独特人群中纳曲酮药物治疗和/或认知行为心理治疗的疗程和结果相关。候选基因和多态性的选择是基于最近的研究，这些研究表明这些遗传变异对某些酒精相关的临床特征有小到中度的影响。除了标准的结果测量之外，我们建议利用一种新颖的数据收集技术，即交互式语音响应，来收集有关情绪、渴望、自我效能、动机和饮酒之间日常关系的数据。为了加强候选人掌握设计和实施临床试验的技能的实习，并测试新药在特定人群中控制饮酒的潜在用途，该研究计划还包括一项针对同一高功能 MSM 问题饮酒群体口服托吡酯（200 毫克/天）有效性和安全性的初步研究。总体而言，研究产生的数据和使用的方法将作为未来 AUD 个性化治疗研究的基础。这项以患者为导向的研究职业奖申请将为训练有素的精神病学家和分子神经科学家 Andrew C. Chen 医学博士、哲学博士提供必要的时间、指导和培训，以开展高质量的临床转化研究，包括药物遗传学方法，以开发酒精使用障碍 (AUD) 的个性化治疗方法。 公共卫生相关性：最近的研究表明，有饮酒问题的人可能对治疗有不同的反应。拟议的 K 奖将使候选人能够研究个体治疗反应的遗传基础。该研究产生的数据和使用的方法将作为未来开发酒精使用障碍个性化治疗的基础。