Clinical Trial: Pharmacogenetics of Nicotine Addiction Treatment

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pharmacogenetics of Nicotine Addiction Treatment (PNAT)

Brief Summary: The purpose of this research program is to understand how a biomarker called the "nicotine metabolite ratio" (also referred to as NMR) may influence a smoker's ability to quit smoking.

Detailed Summary: Smoking is an enormous public health problem with a great need for research to improve treatment outcomes. Our prior data indicates that the cytochrome P450 2A6 (CYP2A6) enzyme is critical in the metabolic inactivation of nicotine, and also influences smoking behavior and response to therapies. With a vision toward translation of our research to practice, we have characterized a genetically-informed biomarker of CYP2A6 activity, specifically the nicotine metabolite ratio (NMR; 3'hydroxycotinine/cotinine), which reflects both CYP2A6 genetic variation and environmental influences on CYP2A6 activity. The NMR is measured non-invasively in smokers with established reliability, stability, analytic validity, and efficacy as a predictor of the ability to quit smoking and treatment response in multiple retrospective trials. Translation of these findings to clinical practice requires validation in a prospective clinical trial comparing alternative therapies for smoking cessation. Thus, the proposed trial is a prospective, stratified, placebo-controlled, multi-center clinical trial of alternative therapies for smoking cessation treatment in approximately 1,200 smokers. Randomization to placebo (PLA), transdermal nicotine (TN), or varenicline (VAR) will be stratified prospectively based on the nicotine metabolite ratio (NMR). Abstinence from smoking at the end of treatment will be the primary outcome. Quit rate at 6-month follow-up is a secondary outcome. To facilitate translation to practice, analysis of the cost-effectiveness of our proposed approach will also be completed. The proposed research provides the next critical step to validate a genetically-informed diagnostic tool, the NMR, which clinicians can use in the future to optimize treatment decisions for their patients who wish to quit smoking.
Sponsor: University of Pennsylvania

Current Primary Outcome: 7-day Point Prevalence Quit Rate at End-of-Treatment (EOT) [ Time Frame: Week 11 ]

The percentage of ITT subjects who were verified as abstinent. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers.


Original Primary Outcome: 7-day point prevalence quit rate [ Time Frame: 7 days ]

The definition of this measure requires: (a) no self-reported smoking (not even a puff of a cigarette) for at least the 7 days prior to the assessment, and (b) biochemical verification of abstinence.


Current Secondary Outcome:

  • 7-day Point Prevalence Quit Rate at 6-month Follow up Survey [ Time Frame: Week 24 ]
    The percentage of ITT subjects who were verified as abstinent at the 6-month follow up survey. Abstinence was defined as no self-reported smoking (not even a puff) for at least 7 days before the telephone assessment, with in-person verification for those self-reporting abstinence. In-person verification consisted of breath carbon monoxide analysis, with a reading of 8 parts-per-million or less confirming abstinence. Subjects who were lost to follow-up were considered smokers.
  • Total Side-Effect Severity Index at Pre-Quit [ Time Frame: Pre-Quit (Week -1/Baseline) ]

    The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers).

    Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects.

  • Total Side-Effect Severity Index at Target Quit Date [ Time Frame: Target Quit Date (Week 0) ]

    The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers).

    Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects.

  • Total Side-Effect Severity Index at Week 1 [ Time Frame: Week 1 ]

    The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers).

    Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects.

  • Total Side-Effect Severity Index at Week 4 [ Time Frame: Week 4 ]

    The mean side-effect severity score by treatment group (placebo vs. nicotine patch vs. varenicline) and by NMR group (slow metabolizers vs. normal metabolizers).

    Side-effect severity was calculated using a Side Effects Checklists (SEC). 29 common side-effects associated with transdermal nicotine or varenicline treatment were rated by participants on a 0 (none) to 3 (severe) scale. For each participant at this timepoint, these scores were summed to calculate a total score, with a range of 0 to 87; a higher score indicated a higher severity of side-effects.



Original Secondary Outcome:

  • Continuous Abstinence (11 weeks) [ Time Frame: 11 weeks ]
    The definition of this measure requires: Not taking even 1 cigarette puff from target quit date to end of treatment.
  • Cost-effectiveness Ratio [ Time Frame: 12 weeks ]
    Incremental cost-effectiveness ratio (ICER) will be calculated as a ratio of the difference between mean costs in each treatment group and the difference between the cessation rates across the treatment arms at weeks 11, 24 and 52.
  • Time to Relapse [ Time Frame: 11 weeks ]
    The definition of this measure is the number of consecutive days of abstinence following target quit date.


Information By: University of Pennsylvania

Dates:
Date Received: March 10, 2011
Date Started: December 2010
Date Completion:
Last Updated: February 3, 2016
Last Verified: February 2016