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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(申请人提供)：这项探索性发展研究的主要目的将是为未来的R01进行药物遗传学(PGx)随机对照戒烟试验奠定基础-纳入以患者为中心的有效遗传反馈(GF)动机增强干预。进行可行性试验的理由有三个。首先，来自多项研究的聚合数据表明，观察到的结果是重复的，即低活性多巴胺能遗传变异(例如，ANKK1/“DRD2”Taq1AA1等位基因)与更好的尼古丁替代疗法(NRT)疗效相关，而高活性变异(例如，Taq1AA2等位基因)与更大的缓释安非他酮(BUP)戒烟疗效相关。其次，PGx戒烟疗法目前直接销售给吸烟者，而没有经过前瞻性试验证明其安全性和有效性。最后，到目前为止，唯一发表的关于GF对戒烟PGx疗法的心理和行为影响的研究都使用了非临床环境中的假设性案例研究。因此，我们的跨学科团队在PGx、临床试验、生物标记物信息激励增强、定性方法和生物医学伦理学方面拥有专业知识，提出了以下具体目标：目标1：开展形成性研究，以扩展的平行过程模型为基础，开发和完善多组分戒烟干预的临床方案，包括PGx治疗和GF：我们将通过对20名非裔美国人和欧洲血统的吸烟者进行形成性访谈，调整、中试和完善理论上有基础的PGx戒烟干预措施。目的：进行一项混合方法的可行性试验，将寻求戒烟治疗的吸烟者随机分为联合治疗组和非治疗组，以检验新开发的戒烟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：吸烟者(N=100)将被随机分为治疗组和不治疗组，所有吸烟者都将接受激励性访谈(标准护理/SC)和PGx治疗。我们将评估GF对复发时间、用药依从性的影响，以及对治疗过程和认知、心理和行为结果的全面评估。最后，我们将综合定量和定性数据来修改方案，生成假设，并估计后续R01提交的效果大小。我们假设，在接受PGx和SC治疗的吸烟者中，基因反馈的增加将与更长的复发时间和服药依从性相关；我们将探索GF是否提高了自我效能、戒烟信心和对戒烟的感知控制，从基线到治疗期间和治疗结束时的随访评估。公共卫生相关性：该项目的结果将支持我们对预期的基因定制戒烟疗法进行大规模随机临床试验的能力，该试验将作为R01提案提交。这些结果将有助于将越来越多的药物遗传学信息从回顾性研究转化为最终目标，即开发以证据为基础、以患者为中心的个性化戒烟疗法，在提高疗效的同时将不良心理或行为后果的风险降至最低。