Project 1 - Clinical Trials

该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 停止治疗。我们开发并验证了第一个基于证据的算法， 戒烟治疗对吸烟者的基线特征及其对治疗的初始治疗反应的影响 4年来，我们一直在为NIDA提供支持。我们将在此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）妇女关注 戒烟后体重增加，在以前的研究中已经表明，特别容易复发 戒烟后。我们将评估lorcaserin的疗效，lorcaserin是一种5-HT 2C激动剂，FDA批准用于治疗 减肥，这已被我们中心的临床前研究表明，以减少尼古丁自我管理。一 将关注戒烟后体重增加的女性样本随机分为接受氯卡色林和 安慰剂胶囊; 2）吸烟者，他们对吸烟的吸入方面很重要，这是一种不需要的需求 通过常规尼古丁替代疗法（NRT）很好地解决。电子尼古丁传送系统 （“ENDS”）提供尼古丁和吸烟行为的关键吸入方面的替代， 在戒烟治疗中显示出希望。在一个吸烟者的样本中， 吸烟对他们很重要，我们将评估ENDS单独或与NRT联合使用的疗效 与单独NRT相比; 3）吸烟者对戒烟的负面情绪后果表示担忧 吸烟，这会增加复发的风险。在这些吸烟者中，我们将评估阿米替定的疗效， 一种具有抗抑郁作用的三重降钙素-去甲肾上腺素-多巴胺再摄取阻滞剂。阿米替丁具有 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方法。吸烟者将 随机分为三组，分别接受两种活性剂量的阿米替定或安慰剂。的每一个中 在上述临床试验中，将在治疗第一周后使用基于实验室的 模式，以确定和验证治疗结果的早期标志物。这些措施包括随意吸烟， 情绪，渴望和戒断症状，以及在模拟吸烟失误中避免吸烟的能力 范例我们将把治疗结果与这些对治疗的初步反应的衡量标准联系起来。 此外，我们将戒烟结果与吸烟者的基线特征相关联，包括 人口统计学变量、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，我们将促进快速筛选新的候选治疗方法， 帮助确定哪些治疗方法最有可能帮助特定的吸烟者亚群实现长期吸烟 戒烟与评估上述候选治疗的功效一起， 该项目可能会提供有价值的新的治疗方法和框架，以帮助指导他们的研究。 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.