Balanced Placebo Design with Varenicline: Pharmacological and Expectancy Effects on Medication Adherence

伐尼克兰的平衡安慰剂设计：对药物依从性的药理学和预期影响

基本信息

批准号：
9753708
负责人：
Samantha P Yeager
金额：
$ 3.45万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-09 至 2021-07-08
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9753708
关键词：
Abstinence Accounting Adherence Adult Aftercare Agonist Behavior Therapy Bupropion Cellular Phone Cessation of life Chantix Cigarette Smoker Data Analyses Deception Disease Dose Double-Blind Method Ecological momentary assessment Effectiveness Evaluation Expectancy Gender Goals Headache Individual Instruction Intervention Link Mentorship Methodology Nausea Nicotine Withdrawal Outcome Pain Participant Patients Pharmaceutical Preparations Pharmacology Physiological Placebo Effect Placebos Race Randomized Relapse Reporting Research Sleeplessness Smoker Smoking Stomach Symptoms Testing Therapeutic Therapeutic Effect Time Training United States Withdrawal Symptom cigarette smoke cigarette smoking design effective therapy experience improved medication administration medication compliance medication nonadherence nicotine replacement preventable death research and development research data dissemination side effect smoking cessation symptom treatment varenicline

项目摘要

Smoking continues to be the leading cause of preventable death in the U.S., accounting for one in five deaths each year. Varenicline (Chantix) is a partial nicotinergic agonist and is the most efficacious monotherapy for successful smoking cessation; however, long-term abstinence with varenicline only ranges from 20% – 40%. One contributing factor to this low effectiveness may be poor medication adherence due to nonspecific side effects (i.e., side effects not explained by the pharmacology of the medication, but possibly due to negative medication expectancies or nicotine withdrawal symptoms that are mistakenly attributed to medication use). Nonspecific side effects have been linked to negative outcomes such as nonadherence, discontinuing effective treatment, and attempts to treat these symptoms with additional medications. The current proposal will utilize the double-blind balanced placebo design to differentiate expectancies versus pharmacologic mechanisms of varenicline administered for two weeks to smokers seeking treatment. The double- blind balanced placebo design includes a cross-balanced medication administration (active medication v. placebo) and instructional set (told truth v. deception) resulting in four groups of smokers seeking treatment: (1) told therapeutic dose (TD) medication + received TD medication; (2) told TD medication + received placebo; (3) told low dose (LD) medication+ received TD dose medication; (4) told LD medication + received placebo. Ecological momentary assessments (EMA) in the form of Daily Dairies delivered via smartphone will assess real-time side effects, withdrawal symptoms, cigarettes smoked, medication use, and reasons for medication non-adherence. The specific aims for this proposal will examine the main effects and interaction of instructional set and pharmacology on medication adherence (Aims 1 and 2) and evaluate moderators of pharmacology and expectancy effects on medication adherence (Exploratory Aim). Assessing expectancies and physiological barriers (i.e., non-specific side effects) to varenicline medication adherence will identify targets to improve medication adherence and to develop behavioral interventions that can modify and reframe negative expectancies and experiences. The specific aims of this project will be completed in conjunction with a formal training plan, sponsored by Dr. Karen Cropsey, Dr. Peter Hendricks, Dr. Michael Businelle, Dr. Richard Shelton, and Dr. Sylvie Mrug. This training plan includes: 1) pharmacological research development, 2) EMA methodology, 3) advanced longitudinal data analysis, and 4) research dissemination and mentorship.

吸烟仍然是美国可预防死亡的主要原因，占美国四分之一 Varenicline (Chantix) 是一种部分烟碱能激动剂，每年导致 5 人死亡。成功戒烟的有效单一疗法；然而，长期戒烟伐尼克兰的作用范围仅为 20% – 40%，造成这种低有效性的一个因素可能是。由于非特异性副作用（即无法用药物解释的副作用）导致服药依从性差药物的药理学，但可能是由于负面的药物预期或尼古丁被错误地归因于药物使用的戒断症状）。与不良后果有关，例如不依从、停止有效治疗，以及尝试用额外的药物治疗这些症状。双盲平衡安慰剂设计，以区分期望与药理学伐尼克兰对寻求治疗的吸烟者施用两周的机制。盲平衡安慰剂设计包括交叉平衡药物管理（主动药物与安慰剂）和教学集（告诉真相与欺骗）导致四组寻求治疗的吸烟者：(1) 告知治疗剂量 (TD) 药物 + 接受 TD 药物；(2) 告知 TD 药物 + 接受安慰剂；(3) 告知低剂量 (LD) 药物 + 接受 TD 剂量；药物治疗；（4）告诉LD药物治疗+接受安慰剂。通过智能手机提供的每日乳制品形式将评估实时副作用、戒断情况症状、吸烟情况、药物使用情况以及不依从药物治疗的原因。该提案的具体目标将审查教学设置和教学的主要影响和相互作用。药理学对药物依从性的影响（目标 1 和 2）并评估药理学调节因素以及对药物依从性的预期影响（探索性目标）。伐尼克兰药物依从性的生理障碍（即非特异性副作用）将确定目标是提高药物依从性并制定可以改变和改变的行为干预措施重新构建负面期望和经验。该项目的具体目标将在年内完成。与正式培训计划相结合，由 Karen Cropsey 博士、Peter Hendricks 博士、 Michael Businelle、Richard Shelton 博士和 Sylvie Mrug 博士该培训计划包括：1) 药理学研究进展，2) EMA 方法，3) 高级纵向数据分析，4) 研究传播和指导。