Clinical Trials

目前的戒烟治疗对大多数吸烟者无效。因此，迫切需要 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 对照临床试验，旨在评估增强适应性治疗策略的疗效， 戒烟。我们独特的适应性治疗方法的本质是开始治疗， 最先进的尼古丁替代疗法（NRT），在目标戒烟前2周开始 约会我们随后将根据吸烟者对NRT的初始反应调整治疗方法， 在目标戒烟日期之前评估的其他基线变量。我们的首要假设是， 通过调整基于个体受试者的药理学治疗来提高戒烟效果 吸烟者在接受戒烟前NRT期间的特征和随意吸烟。研究1， 将在第1-3年进行，将评估一个具体的两阶段适应性治疗算法。我们将发起 在目标戒烟日期前2周进行戒烟前尼古丁贴片治疗。如果一周后 暴露于NRT，受试者未显示出有利的治疗反应（通过早期结局评估 在戒烟日期前减少随意吸烟的标志），他们将被随机接受“补救”治疗 用安非他酮SR（Zyban）、伐尼克兰（Chantix）治疗，或将保持NRT（对照）。研究2，待 在第4-5年进行，将使用相同的适应性治疗评价其他候选药物 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 其他中心项目的临床证据以及其他实验室的发现，使用标准 在研究计划中描述。候选药物将包括神经类固醇DHEA和 异烯醇酮、其他GABA能、谷氨酸能或单胺能药物以及烟碱亚型 选择性配体个体受试者的信息将增强临床试验决策和结果 特征，包括戒烟成功的基因型，依赖程度，性别，以及精神和 物质使用合并症。这些基线特征和吸烟的综合信息 在戒烟前NRT可能提供了强大的预测药物和治疗 对于不同的吸烟者，方案最有可能成功。从这些研究中获得的知识将 提供了一种重要的新的治疗方法，以指导卫生保健提供者提供最有效的 戒烟治疗是最适合每个吸烟者的需要。

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.