Project 1 - Clinical Trials

这个临床试验项目将评估几种创新的、个性化的和适应性的吸烟方法 戒烟治疗。我们开发并验证了第一个基于证据的吸烟定制算法 戒烟治疗对吸烟者基线特征和治疗初期疗效的影响 我们之前4年的NIDA支持。我们将在这一进展的基础上，探索三种新的治疗方法 寻求使以下不同的吸烟者群体受益的方法：1)关注 戒烟后体重增加，以前的研究表明他们特别容易复发 戒烟后。我们将评估氯卡瑟林的疗效，这是一种5-HT2C激动剂，FDA批准用于 减肥，我们中心的临床前研究表明，这可以减少尼古丁的自我给药。一个 关注戒烟后体重增加的女性样本将被随机分为服用氯卡司林组和对照组。 安慰剂胶囊；2)吸烟的吸入性方面对他们来说很重要的吸烟者，但这一需求并不重要 传统的尼古丁替代疗法(NRT)很好地解决了这一问题。电子尼古丁输送系统 (“Ends”)提供尼古丁和吸烟行为的关键吸入方面的替代品，并具有 在戒烟治疗中表现出了希望。在一组吸烟者中，他们报告了吸入的方面 吸烟对他们来说很重要，我们将评估END单独或与NRT联合使用的效果 与NRT相比；以及3)对戒烟的负面情绪后果表示担忧的吸烟者 吸烟，这会增加复发的风险。在这些吸烟者中，我们将评估阿米替法定的疗效，一种 具有抗抑郁作用的三重5-羟色胺-去甲肾上腺素-多巴胺再摄取阻滞剂。阿米替法定有 在我们中心的临床前研究中也发现了减少尼古丁自我给药的作用。吸烟者将会是 随机分成三组，接受两种有效剂量的阿米替法丁或安慰剂中的一种。在每一个 在上述临床试验中，参与者将在治疗的第一周后接受评估，使用基于实验室的 识别和验证治疗结果的早期标志物的范例。这些措施包括随意吸烟， 情绪、渴望和戒断症状，以及在模拟吸烟过程中戒烟的能力 范例。我们将把治疗结果与治疗初始反应的这些指标联系起来。 此外，我们将把戒烟结果与吸烟者的基线特征联系起来，包括 人口统计变量、吸烟史和先前研究中确定的遗传标记。通过验证标记 预测治疗结果，我们将促进新的候选治疗方法的快速筛选和 帮助确定哪些治疗方法最有可能帮助特定的吸烟者实现长期戒烟 戒烟。连同评估上述候选治疗的疗效，这一点 该项目可能会贡献有价值的新治疗方法和框架，以帮助指导他们的 向目标吸烟者亚群传播。

This Clinical Trials project will evaluate several innovative, personalized and adaptive approaches to smoking cessation treatment. We developed and validated the first evidence-based algorithm for tailoring smoking cessation treatment to smokers’ baseline characteristics and their initial therapeutic response to treatment with our previous 4 years of NIDA support. We will build on this progress by exploring three novel therapeutic approaches that seek to benefit the following distinct populations of smokers: 1) women concerned about weight gain after quitting smoking, who have been shown in previous studies to be especially prone to relapse after quitting smoking. We will evaluate the efficacy of lorcaserin, a 5-HT2C agonist that is FDA-approved for weight loss, which has been shown by our Center’s Preclinical Studies to reduce nicotine self-administration. A sample of women concerned about post-cessation weight gain will be randomized to receiving lorcaserin vs. placebo capsules; 2) smokers for whom the inhalational aspects of smoking are important, a need that is not well addressed by conventional nicotine replacement therapy (NRT). Electronic nicotine delivery systems (“ENDS”) provide replacement of both nicotine and key inhalational aspects of smoking behavior and have shown promise in smoking cessation treatment. In a sample of smokers who report inhalational aspects of smoking to be important to them, we will evaluate the efficacy of ENDS alone or in combination with NRT compared to NRT alone; and 3) smokers who express concern about negative mood consequences of quitting smoking, which confers greater risk of relapse. In these smokers, we will evaluate the efficacy of amitifadine, a triple serotonin-norepinephrine-dopamine reuptake blocker that has antidepressant effects. Amitifadine has also been found in our Center’s Preclinical Studies to reduce nicotine self-administration. Smokers will be randomized into three groups receiving one of the two active doses of amitifadine or placebo. In each of the above clinical trials, participants will be evaluated after the first week of treatment, using a laboratory-based paradigm to identify and validate early markers of treatment outcome. These measures include ad lib smoking, mood, craving and withdrawal symptoms, and the ability to refrain from smoking in a simulated smoking lapse paradigm. We will correlate treatment outcome with these measures of the initial response to treatment. Additionally, we will correlate abstinence outcomes with smokers’ baseline characteristics, including demographic variables, smoking history, and genetic markers identified in prior studies. By validating markers predictive of treatment outcome, we will both facilitate the rapid screening of novel candidate treatments and help identify which treatments will be most likely to help specific subpopulations of smokers achieve long-term smoking abstinence. Together with evaluating the efficacy of the candidate treatments described above, this project will likely contribute valuable new therapeutic approaches and a framework to help guide their dissemination to targeted subpopulations of smokers.