Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence

Cigarette Smoking Clinical Trial

— NMR  

Official title:

Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01627392
• Other study ID #: 12-08635
• Status: Completed
• Phase: N/A
• First received: June 14, 2012
• Last updated: December 1, 2015
• Start date: July 2012
• Est. completion date: August 2015

Study information

• Verified date: December 2015
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 305
• Est. completion date: August 2015
• Est. primary completion date: August 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Cigarette Smoking

Intervention

Behavioral:
• Smoking abstinence
6 hour smoking abstinence

Locations

Country	Name	City	State
United States	San Francisco General Hospital	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
University of California, San Francisco

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nicotine withdrawal symptoms	Total withdrawal score as measured by Minnesota Nicotine Withdrawal Scale	6 hours post nicotine load	No
Secondary	Cognitive performance	Cognitive performance will be measured by n-back computerized testing	6 hours post nicotine load	No
Secondary	Smoking behavior: number of cigarettes	Smoking behavior will be measured by number of cigarettes during a monitoring period following the 3rd (reward) cigarette of the protocol	90 minutes post-abstinence	No
Secondary	Smoking behavior: number of puffs per cigarette	Smoking behavior will be measured by number of puffs per cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol	90 minutes post-abstinence	No
Secondary	Smoking behavior: time to first post-reward cigarette	Smoking behavior will be measured by time to first post-reward cigarette during a monitoring period following the 3rd (reward) cigarette of the protocol	90 minutes post-abstinence	No