Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence (NMR)
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence|
- Nicotine withdrawal symptoms [ Time Frame: 6 hours post nicotine load ] [ Designated as safety issue: No ]Total withdrawal score as measured by Minnesota Nicotine Withdrawal Scale
- Cognitive performance [ Time Frame: 6 hours post nicotine load ] [ Designated as safety issue: No ]Cognitive performance will be measured by n-back computerized testing
- Smoking behavior: number of cigarettes [ Time Frame: 90 minutes post-abstinence ] [ Designated as safety issue: No ]Smoking behavior will be measured by number of cigarettes during a monitoring period following the 3rd (reward) cigarette of the protocol
- Smoking behavior: number of puffs per cigarette [ Time Frame: 90 minutes post-abstinence ] [ Designated as safety issue: No ]Smoking behavior will be measured by number of puffs per cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol
- Smoking behavior: time to first post-reward cigarette [ Time Frame: 90 minutes post-abstinence ] [ Designated as safety issue: No ]Smoking behavior will be measured by time to first post-reward cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol
|Study Start Date:||July 2012|
|Study Completion Date:||August 2015|
|Primary Completion Date:||August 2015 (Final data collection date for primary outcome measure)|
|Experimental: Smoking abstinence||
Behavioral: Smoking abstinence
6 hour smoking abstinence
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01627392
|United States, California|
|San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|Principal Investigator:||Neal L Benowitz, MD||University of California, San Francisco|