Exploratory/Developmental Study of Pharmacogenetic Smoking Cessation Therapy

药物遗传学戒烟疗法的探索性/发展性研究

基本信息

批准号：
7782802
负责人：
SEAN P. DAVID
金额：
$ 25.94万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7782802
关键词：
African American Alleles Behavioral Bioethics Biological Markers Bupropion Caring Case Study Clinical Clinical Protocols Clinical Trials Cognitive Cognitive Therapy Combined Modality Therapy Communication Complex DRD2 gene Data Development Dopamine Dopamine D2 Receptor Environmental Risk Factor European Feedback Funding Future Genetic Genetic Polymorphism Genotype Goals Guidelines Intervention Interview Investments Marketing Medicine Methods Modeling National Human Genome Research Institute Outcome Outcome Measure Outcomes Research Participant Patients Pharmacogenetics Placebos Preparation Process Protocols documentation Psychological Impact Publishing Qualitative Methods Randomized Randomized Clinical Trials Randomized Controlled Trials Relapse Relative (related person)Research Retrospective Studies Risk Safety Self Efficacy Smoker Smoking Cessation Intervention Staging Stream Subgroup Testing Time Tobacco smoking Translations Treatment Efficacy Variant arm base biobehavior care systems clinical practice drug efficacy ethical legal social implication evidence base evidence based guidelines follow up assessment follow-up genetic variant ideation improved interest medication compliance meetings mortality motivational enhancement therapy nicotine replacement parallel processing patient oriented premature primary care setting primary outcome prospective psychologic public health relevance randomized trial response satisfaction secondary outcome smoking cessation standard care

项目摘要

DESCRIPTION (provided by applicant): The major purpose of this exploratory developmental study will be to lay the groundwork for a future R01 to conduct a pharmacogenetic (PGx) randomized controlled trial of smoking cessation - incorporating a patient- centered and effective genetic feedback (GF) motivational enhancement intervention. The rationale for conducting a feasibility trial is three-fold. First, converging data from multiple studies demonstrate replication of the observation that low activity dopaminergic genetic variants (e.g., ANKK1/ "DRD2" Taq1A A1 alleles) are associated with greater nicotine replacement therapy (NRT) efficacy and higher activity variants (e.g., Taq1A A2 alleles) are associated with greater sustained-release bupropion (BUP) efficacy for smoking cessation. Secondly, PGx smoking cessation therapies are currently directly marketed to smokers without evidence of safety and efficacy from prospective trials. Finally, to date, the only published studies of the psychological and behavioral impact of GF for smoking cessation PGx therapies have used hypothetical case studies in non- clinical settings. Therefore, our transdisciplinary team with expertise in PGx, clinical trials, biomarker-informed motivational enhancement, qualitative methods, and biomedical ethics, proposes the following specific aims: Aim 1: Conduct formative research to develop and refine a clinical protocol for a multi-component smoking cessation intervention, grounded in the extended parallel process model, consisting of PGx treatment and GF: We will adapt, pilot-test, and refine a theoretically-grounded PGx smoking cessation intervention using formative interviews of 20 African-American and European-ancestry smokers. Aim 2: Conduct a mixed-methods feasibility trial randomizing treatment-seeking smokers to PGx treatment combined with GF vs. PGx treatment without GF for smoking cessation to examine the feasibility of the newly developed protocol in a primary care setting and characterize its psychological and behavioral impact: Smokers (N = 100) will be randomized to GF vs. no GF and all will receive motivational interviewing (standard care/SC) and PGx treatment. We will assess the impact of GF on time to relapse, medication adherence, and a comprehensive assessment battery of process and cognitive, psychological, and behavioral outcomes. Finally, we will synthesize quantitative and qualitative data to revise protocols, generate hypothesizes, and estimate effect sizes for a follow-up R01 submission. We hypothesize that amongst smokers receiving PGx and SC, the addition of genetic feedback will be associated with increased time to relapse and medication adherence; and we will explore whether or not GF enhances self-efficacy, smoking cessation confidence, and perceived control over smoking cessation from baseline to follow-up assessments during treatment and at the end of treatment. PUBLIC HEALTH RELEVANCE: The results from this project will support our ability to conduct a large-scale, randomized clinical trial of prospective genetically tailored smoking cessation therapies, to be submitted as an R01 proposal. These results will facilitate the translation of the growing body of pharmacogenetic information from retrospective studies toward the ultimate goals of developing evidence-based, patient-centered, personalized smoking cessation therapies that enhance efficacy while minimizing the risk of adverse psychological or behavioral outcomes.

描述（由申请人提供）：这项探索性发育研究的主要目的是为未来的R01奠定基础，以进行药物遗传学（PGX）戒烟的随机对照试验 - 结合患者中心且有效的遗传反馈（GF）动机增强措施。进行可行性试验的理由是三倍。首先，来自多项研究的收敛数据表明，观察到低活性多巴胺能遗传变异（例如ANKK1/“ DRD2” TAQ1A A1等位基因）与较高的尼古丁替代治疗（NRT）功效（NRT）疗效和较高的活性变体（例如TAQ1A A2 AlbeS ectigention（BB）与较高的效果相关联（BB）与较高的效果相关联（bec1a A2 Alleles）与更大的效果有关戒烟。其次，PGX戒烟疗法目前直接向吸烟者销售，而没有前瞻性试验的安全性和功效证据。最后，迄今为止，关于GF对戒烟PGX疗法的心理和行为影响的唯一发表的研究已经在非临床环境中使用了假设的案例研究。因此，我们的跨学科团队在PGX，临床试验，生物标志物具有的动机增强，定性方法和生物医学伦理方面具有专业知识，提出了以下具体目的：目标1：进行形成性研究，以开发和完善一项临床研究和完善临床方案，以进行多组分的烟雾及其在pg cess的临床方案，在pgx，pgx，pg cess and the the Gret the Gret where the Gret parlall od Gets and Plallatel parlall of Plallatel parlall of Plallate of plallay of plallate of p. we we we and of the cess cess：试点测试，并通过对20名非裔美国人和欧洲裔吸烟者的形成性访谈来完善理论上的PGX戒烟干预措施。目标2：进行混合方法可行性试验随机将寻求治疗的吸烟者与GF与PGX治疗相结合而无需GF治疗，而无需GF进行戒烟，以检查新开发方案在初级保健环境中的可行性，并表征其心理和行为影响的特征：吸烟者（n = 100）将对GF进行gf和pg的治疗（pg vss）。我们将评估GF对复发，药物依从性以及过程以及认知，心理和行为结果的全面评估电池的影响。最后，我们将综合定量和定性数据以修改协议，生成假设并估计效应大小，以进行后续R01提交。我们假设在接受PGX和SC的吸烟者中，遗传反馈的增加将与增加的复发时间和药物依从性有关；我们将探讨GF是否增强了自我效能感，戒烟信心以及对从基线到治疗期间和治疗结束时对吸烟戒烟的控制的控制。公共卫生相关性：该项目的结果将支持我们进行大规模，随机临床试验的能力，以作为R01提案提交的前瞻性基因量身定制的戒烟疗法。这些结果将有助于从回顾性研究中转化出不断增长的药物遗传信息体系，以开发基于循证的，以患者为中心的个性化戒烟疗法的最终目标，从而提高疗效，同时最大程度地减少不良心理或行为成果的风险。