Clinical trial NCT01627392: Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
Official title: Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cigarette Smoking
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2012-06-25
Enrollment: 305
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Nicotine withdrawal symptoms
timeFrame: 6 hours post nicotine load
Secondary outcomes:
measure: Cognitive performance
timeFrame: 6 hours post nicotine load
measure: Smoking behavior: number of cigarettes
timeFrame: 90 minutes post-abstinence
measure: Smoking behavior: number of puffs per cigarette
timeFrame: 90 minutes post-abstinence
measure: Smoking behavior: time to first post-reward cigarette
timeFrame: 90 minutes post-abstinence
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
Study officials:
affiliation: University of California, San Francisco
name: Neal L Benowitz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nardone N, Shahid M, Strasser AA, Dempsey DA, Benowitz NL. The influence of nicotine metabolic rate on working memory over 6 hours of abstinence from nicotine. Pharmacol Biochem Behav. 2020 Jan;188:172836. doi: 10.1016/j.pbb.2019.172836. Epub 2019 Dec 5.
citation: Liakoni E, Edwards KC, St Helen G, Nardone N, Dempsey DA, Tyndale RF, Benowitz NL. Effects of Nicotine Metabolic Rate on Withdrawal Symptoms and Response to Cigarette Smoking After Abstinence. Clin Pharmacol Ther. 2019 Mar;105(3):641-651. doi: 10.1002/cpt.1238. Epub 2018 Oct 25.