Our goal is to identify the most appropriate smoking cessation treatments for smokers based
on genetic information. Smokers try to quit smoking but relapses are common.
Our goal is to determine whether genetic markers can be used to optimize smoking cessation
pharmacotherapy to enhance efficacy, medication adherence, and reduce side effects. Smoking
is a leading cause of preventable death and disability, and smoking cessation reverses the
risk of mortality. However, cessation failure is common despite available cessation
medications, which are associated with different efficacy, side effects, adherence, use
constraints, and costs. This challenge can be addressed by improving current treatments via
personalized medicine based on individual genetic markers to maximize efficacy and minimize
We propose a prospective, genotype-based stratified randomization trial to compare two
smoking cessation medications (combination NRT [patch and lozenge], varenicline vs. placebo)
for 3 months in 720 smokers with known genotypes. This study uses a stratified randomization
trial design based on a subject's pertinent genotype for smoking cessation. Specifically, in
Aim 1, we will determine if CHRNA5 genotype moderates the effect of medication (combination
NRT, varenicline, vs. placebo) on abstinence. In Aim 2, we will determine if CHRNA5 genotype
predicts medication adherence and side effects. In Aim 3, we will incorporate multiple
genotypes and other predictors in order to develop a clinical treatment assignment algorithm
for cessation success. This work can result in improved physician care of patients who
smoke, overall smoking cessation success, and prevention of cancer, heart, and lung disease.
1. Adult (≥21 years of age), seeking treatment for smoking cessation.
2. Able to speak English,
3. Active smoking (Cigarettes Per Day (CPD) >=5), and exhaled Carbon Monoxide (CO) >=8
4. Agree to participate in this randomized smoking cessation trial with follow up
assessments up to 12 months.
1. Pregnancy or breast feeding,
2. Active use or recent use (< or equal to 1 month) of medication or e-cigarettes for
nicotine dependence/smoking cessation, or use of e-cigarettes for more than 9 days in
the prior month,
3. Allergy to nicotine patch, lozenge, or varenicline,
4. Unwillingness to prevent pregnancy during the medication phase and 1 month afterwards
5. Significant cardiac conditions (myocardial infarction, unstable angina, coronary
angioplasty, cardiac bypass) or serious arrhythmia in past 6 months,
6. Current heavy alcohol consumption (≥6 drinks/day, 6 days/week),
7. Active psychosis or poorly controlled depression within the past 6 months,
8. Any prior suicide attempt or suicidal ideation within the past 6 months,
9. End stage renal disease with hemodialysis.