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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 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: August 18, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention
Cigarette Smoking
Behavioral: Smoking abstinence

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 320
Study Start Date: July 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Smoking abstinence Behavioral: Smoking abstinence
6 hour smoking abstinence

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01627392

Locations
United States, California
San Francisco General Hospital Recruiting
San Francisco, California, United States, 94110
Contact: Marian Shahid    415-476-3555      
Principal Investigator: Neal Benowitz, MD         
Sponsors and Collaborators
University of California, San Francisco
Investigators
Principal Investigator: Neal L Benowitz, MD University of California, San Francisco
  More Information

No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT01627392     History of Changes
Other Study ID Numbers: 12-08635
Study First Received: June 14, 2012
Last Updated: August 18, 2014
Health Authority: United States: Federal Government

ClinicalTrials.gov processed this record on September 30, 2014