Pharmacogenetics of Nicotine Addiction Treatment (PNAT)
Smoking is an enormous public health problem with a great need for research to improve
treatment outcomes. Our prior data indicates that the 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 1,350 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. 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.
Interventional
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment
7-day point prevalence quit rate
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.
Week 12
No
Caryn Lerman, PhD
Principal Investigator
University of Pennsylvania
United States: Food and Drug Administration
811722
NCT01314001
January 2011
August 2014
Name | Location |
---|---|
MD Anderson Cancer Center, University of Texas | Houston, Texas 77030 |
University at Buffalo - State University of New York | Buffalo, New York 14260 |
Center for Interdisciplinary Research on Nicotine Addiction, University of Pennsylvania | Philadelphia, Pennsylvania 19104 |