Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence (NMR)

This study is currently recruiting participants.
Verified January 2014 by University of California, San Francisco
Sponsor:
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT01627392
First received: June 14, 2012
Last updated: January 21, 2014
Last verified: January 2014

June 14, 2012
January 21, 2014
July 2012
May 2014   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01627392 on ClinicalTrials.gov Archive Site
  • 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 [ Time Frame: 6 hours post nicotine load ] [ Designated as safety issue: No ]
    Smoking behavior (number of cigarettes, number of puffs per cigarette, time to first post-reward cigarette) will be assessed during a 90-minute monitoring period following the 3rd (reward) cigarette of the protocol
Same as current
Not Provided
Not Provided
 
Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence
Mechanisms of the Nicotine Metabolism Effect on Tobacco Dependence

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.

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.

Interventional
Not Provided
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Cigarette Smoking
Behavioral: Smoking abstinence
6 hour smoking abstinence
Experimental: Smoking abstinence
Intervention: Behavioral: Smoking abstinence
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
320
June 2015
May 2014   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
Yes
Not Provided
United States
 
NCT01627392
12-08635
No
University of California, San Francisco
University of California, San Francisco
Not Provided
Principal Investigator: Neal L Benowitz, MD University of California, San Francisco
University of California, San Francisco
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP