Pharmacogenetics of Nicotine Addiction Treatment
Condition: Nicotine Addiction
MeSH terms: Tobacco Use Disorder; Behavior, Addictive
Study type: Interventional
Phase: Phase 3

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 description: 
      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.
    

Intervention name(s): Varenicline; Placebo; Transdermal Nicotine
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally; Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally
Week 1 - 6: 21mg placebo patch Week 7 - 8: 14mg placebo patch Week 9 - 11: 7mg placebo patch; Week 1-6: 21mg nicotine patch Week 7-8: 14mg nicotine patch Week 9-11: 7mg nicotine patch
Other intervention name(s): Chantix; Placebo pills; Placebo patches; Nicoderm CQ; Nicotine Patch
Intervention MeSH terms: Nicotine; Varenicline
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Tobacco, Smoking, Varenicline, Nicotine Patch