Improved Human Screening of Cessation Medications

改进戒烟药物的人体筛查

• 批准号: 7289194
• 负责人: KENNETH Alan PERKINS
• 金额: $ 21.18万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7289194
• 关键词: attention deficit disorder; behavioral /social science research tag; craving; depression; disease /therapy duration; drug /alcohol abstinence; drug withdrawal; gender difference; health behavior; health care service utilization; human genetic material tag; human therapy evaluation; motivation; nicotine replacement; pharmacogenetics; reinforcer; smoking; substance abuse related behavior; therapy compliance; therapy design /development

Current treatments for smoking cessation fail most of the time, and robust new treatments, including medications, are sorely needed. Because ofthe substantial costs and time involved in clinical trials, medications subjected to these trials must be those with the greatest promise of success. The purpose of medication screening studies is to quickly and cheaply evaluate the clinical potential of medications, so that promising drugs proceed to clinical trials and unpromising drugs do not. However, there is no human screening procedure for medications in which results are clearly predictive of smoking cessation outcome in clinical trials with those medications. This proposal aims to improve procedures for human screening of potential medications for smoking cessation prior to clinical trials of the efficacy of those medications. Logically, studies on human screening of cessation medications should simulate, within practical limitations, clinical trial procedures. Thus, emphasis should be placed on smoking abstinence as the primary index of medication response, as there are no other clear short-term predictors of long-term abstinence. We will examine sensitivity to medication effects as a function of two methods used to increase the motivation and likelihood of abstinence in smokers participating in a short-term screening study: 1) ?natural? motivation due to treatment seeking status of participants, and 2) ?artificially supported? motivation using monetary incentives contingent on smoking abstinence. We will assess 160 treatment-seeking smokers and 160 non-treatment seeking smokers, half of whom will receive monetary reinforcement on a daily basis contingent on being abstinent (verified by expired-air Co <= 8 ppm) and half of whom will not receive reinforcement far abstinence. In these groups, we will compare effects of 5 days? exposure to 21 mg nicotine versus placebo patch, using a within-subjects cross-over design. Our main dependent measures will be days of smoking abstinence and continuous 5-day abstinence (dichotomous outcome), with cigarettes/day, craving, withdrawal, negative affect, and ADHD symptoms as secondary measures. We hypothesize that differences between nicotine vs placebo patch will be greater in treatment seekers than non-seekers, and in those receiving abstinence reinforcement vs no reinforcement. Secondarily, we will examine changes in the magnitude of nicotine effects as a function ofthe duration of exposure to medication across days within the 5-day treatment period, to identify the point of peak early medication effects. Assessment of self-report measures will be conducted in the natural environment, as well as the lab, to determine the influence of method of assessment on medication response. We will also examine individual differences in nicotine responses. Results will provide immediate directions for improving screening evaluations of cessation medications. Future directions include testing the utility of this improved screening procedure with novel medications, the long-range objective. This research will ultimately help us better understand how to more quickly and efficiently evaluate potential medications for smoking cessation, a goal with very high public health significance.

目前的戒烟治疗大多数时候都会失败，因此迫切需要包括药物在内的强有力的新治疗方法。由于临床试验涉及大量成本和时间，因此接受这些试验的药物必须是最有希望成功的药物。药物筛选研究的目的是快速、廉价地评估药物的临床潜力，以便有希望的药物进入临床试验，而没有前景的药物则不会。然而，目前还没有针对药物的人体筛选程序，其结果可以清楚地预测这些药物的临床试验中的戒烟结果。该提案旨在改进在对这些药物的功效进行临床试验之前对潜在戒烟药物进行人体筛选的程序。 从逻辑上讲，戒烟药物的人体筛查研究应该在实际限制内模拟临床试验程序。因此，应强调戒烟作为药物反应的主要指标，因为没有其他明确的长期戒烟的短期预测因素。我们将检查药物效应的敏感性，作为用于增加参与短期筛查研究的吸烟者戒烟动机和可能性的两种方法的函数：1）“自然”？由于参与者寻求治疗的状态而产生的动机，以及 2) “人为支持”？使用金钱激励的动机取决于戒烟。我们将评估 160 名寻求治疗的吸烟者和 160 名未寻求治疗的吸烟者，其中一半将在戒烟后每天接受金钱强化（通过呼出空气 Co <= 8 ppm 验证），其中一半将不会接受金钱强化强化远禁欲。在这些组中，我们将比较 5 天的效果？使用受试者内交叉设计，比较暴露于 21 毫克尼古丁与安慰剂贴片的情况。我们的主要依赖措施是戒烟天数和连续5天戒烟 （二分结果），以香烟/天、渴望、戒断、负面情绪和 ADHD 症状作为次要指标。我们假设尼古丁贴片与安慰剂贴片之间的差异在寻求治疗的人中比不寻求治疗的人中更大，在接受戒断强化的人和没有强化的人中也更大。其次，我们将考察以下方面的变化： 尼古丁效应的强度与 5 天治疗期内接触药物的持续时间的关系，以确定早期药物效应的峰值点。自我报告措施的评估将在自然环境和实验室中进行，以确定评估方法对药物反应的影响。我们将 还检查尼古丁反应的个体差异。结果将为改进戒烟药物的筛查评估提供直接指导。未来的方向包括用新药物测试这种改进的筛查程序的实用性，这是长期目标。这项研究最终将帮助我们更好地了解如何更快地 并有效评估潜在的戒烟药物，这一目标具有非常高的公共卫生意义。