Clinical Trials

目前的戒烟疗法对大多数吸烟者无效。因此，有一个紧急的 需要制定更有效的治疗策略。该项目将包括两个大规模的随机 旨在评估增强型适应性治疗策略的疗效的对照临床试验 戒烟。我们独特的适应性治疗方法的本质是从治疗开始 最先进的尼古丁替代疗法(NRT)，在目标戒烟前两周开始 约会。我们随后会根据吸烟者对NRT的初步反应来调整治疗方法和 在目标戒烟日期之前评估的其他基线变量。我们最重要的假设是我们会 根据不同受试者调整药物治疗以提高戒烟效果 吸烟者在接受戒烟前NRT期间的特征和即兴吸烟。研究1， 将在1-3年内进行，将评估特定的两阶段自适应治疗算法。我们将发起 在目标戒烟日期前两周进行戒烟前尼古丁贴片治疗。如果，在一周后 暴露在NRT下，参与者没有表现出良好的治疗反应(通过早期结果进行评估 戒烟日期前临时吸烟减少的标志)，他们将被随机抽查以接受“救援” 使用安非他酮SR(Zyban)、varenicline(Chantix)或将继续使用NRT(对照)的治疗。研究2，待完成 在第4-5年进行，将使用相同的适应性治疗评估另一种候选药物 策略与研究1相同。候选治疗的选择将基于可用的临床前和 来自其他中心项目的临床证据以及来自其他实验室的发现，使用标准 研究计划中所描述的。候选药物将包括神经类固醇DHEA和 孕烯醇酮、其他GABA能、谷氨酸或单胺能药以及烟碱亚型 选择性配体。临床试验决定和结果将通过个别受试者的信息得到加强 特征，包括戒烟成功的基因类型、依赖程度、性别以及精神疾病和 物质使用合并症。来自这些基线特征和吸烟的综合信息 在停药前NRT很可能提供强有力的预测因子 对于不同的吸烟者，养生法最有可能成功。从这些研究中获得的知识将 提供一种重要的新治疗方法，指导医疗保健提供者提供最有效的 最适合每个吸烟者需要的戒烟治疗。

Current smoking cessation treatments are ineffective for the majority of smokers. Thus there is an urgent need to develop more effective treatment strategies. This project will comprise two large-scale randomized controlled clinical trials designed to evaluate the efficacy of an enhanced adaptive treatment strategy for smoking cessation. The essence of our unique approach to adaptive treatment is to begin treatment with state-of-the-art nicotine replacement therapy (NRT), which is initiated 2 weeks before a target quit-smoking date. We will subsequently adapt the treatment approach based on smokers' initial response to NRT and other baseline variables assessed prior to the target quit date. Our overarching hypothesis is that we will enhance cessation outcomes by adapting phannacologic treatments based on individual subject characteristics and ad lib smoking during the time when smokers are receiving pre-cessation NRT. Study 1, to be conducted in years 1-3, will evaluate a specific two-phase adaptive treatment algorithm. We will initiate pre-cessation nicotine patch treatment 2 weeks before a target quit-smoking date. If, after one week's exposure to NRT, participants do not show a favorable therapeutic response (assessed by the early outcome marker of reduced ad lib smoking before the quit date), they will be randomized to receive "rescue treatments with bupropion SR (Zyban), varenicline (Chantix), or will remain on NRT (control). Study 2, to be conducted in years 4-5, will evaluate an additional candidate medication, using the same adaptive treatment strategy as in Study 1. The selection of the candidate treatment will be based on available preclinical and clinical evidence from the other center projects as well as findings from other laboratories, using criteria described in the Research Plan. Candidate medications will include the neurosteroids DHEA and pregnenolone, other GABAergic, glutamatergic, or monoaminergic agents as well as nicotinic subtype selective ligands. Clinical trial decisions and results will be enhanced by information on individual subject characteristics, including quit success genotypes, dependence level, gender, as well as psychiatric and substance use comorbidities. Combined information from these baseline characteristics and smoking during pre-cessation NRT are likely to provide powerful predictors of which medication and treatment regimens are most likely to succeed for different smokers. The knowledge gained from these studies will provide an important new therapeutic approach to guide health care providers in delivering the most effective cessation treatments that are best adapted to the needs of each smoker.