Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 305
- 试验地点
- 2
- 主要终点
- Nicotine withdrawal symptoms
研究概览
简要总结
The purpose of the study is to learn more about tobacco dependence and nicotine metabolism in African-Americans and whites, by studying to see if how fast a person metabolizes nicotine (how the body breaks down nicotine into inactive compounds) affects how dependent they are on smoking cigarettes. The investigators believe that people with a faster rate of metabolism may have more severe nicotine withdrawal symptoms and also may have a harder time trying to quit smoking.
详细描述
Our studies will use the nicotine metabolite ratio (NMR) (the ratio between the nicotine metabolites 3'hydroxycotinine and cotinine)as a simple and clinically feasible biomarker for the rate of nicotine metabolism. The investigators hypothesize that a faster rate of metabolism leads to faster elimination of nicotine from the body and a more rapid dissipation of brain tolerance to nicotine in the interval between cigarettes, leading in turn to (1) more severe nicotine withdrawal symptoms and (2) greater subjective reward from the cigarette smoked following deprivation. These effects would help to explain why smokers with faster rates of nicotine metabolism have a poorer response to smoking cessation therapy when compared to those with slower rates of metabolism.
The investigators will explore the relationship of the NMR to the endophenotypes of withdrawal, craving and reward, with the assumption that these factors are likely intermediaries for the mechanism linking nicotine metabolism to tobacco dependence and smoking cessation rates with pharmacotherapy. Our study design uses a brief (6 hour) interval of smoking abstinence followed by a "reward" cigarette to elicit the subjective responses relating to withdrawal and reward. Because smoking behavior and severity of nicotine dependence vary by race and sex the investigators will also compare the relationship between NMR and withdrawal and reward in African American vs white smokers and in men vs women.
Secondary analyses will examine whether nicotine half-life mediates the observed effects of NMR on primary response measures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •African-American or Caucasian
- •Age 18-70 years
- •Regular smoker of 5 or more cigarettes per day
- •Saliva cotinine of 100 ng/ml or greater
排除标准
- •Obese (BMI > 38) or underweight (BMI < 17)
- •Major systemic or psychiatric condition
- •Medications that are inducers of CYP2A6
- •History of alcohol abuse
- •Positive drug urine tox test
- •Pregnancy or breast feeding
结局指标
主要结局
Nicotine withdrawal symptoms
时间窗: 6 hours post nicotine load
Total withdrawal score as measured by Minnesota Nicotine Withdrawal Scale
次要结局
- Cognitive performance(6 hours post nicotine load)
- Smoking behavior: number of cigarettes(90 minutes post-abstinence)
- Smoking behavior: number of puffs per cigarette(90 minutes post-abstinence)
- Smoking behavior: time to first post-reward cigarette(90 minutes post-abstinence)