Genetically Informed Smoking Cessation Trial

The investigators' 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 side effects.

The investigators 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.

Inclusion Criteria:

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 ppm

4. Agree to participate in this randomized smoking cessation trial with follow up
assessments up to 12 months.

Exclusion Criteria:

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
(women only),

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.