Varenicline for the Treatment of Smokeless Tobacco
Varenicline for the Treatment of Smokeless Tobacco
Varenicline (Chantix™, Pfizer) is a novel selective nicotinic receptor partial agonist with
 specificity for the α4β2 nicotine acetylcholine receptor that has demonstrated remarkable
 efficacy for increasing long-term tobacco abstinence rates in cigarette smokers. The novel
 mechanism of action of varenicline potentially circumvents the limitations of using nicotine
 replacement therapy or bupropion pharmacotherapy in ST users. The overall goal of this line
 of research is to develop effective pharmacologic treatments for ST users to increase
 long-term (≥ 6 months) abstinence rates. The central hypothesis of this application is that
 varenicline is efficacious for the treatment of ST users.
In the United States, approximately 7.7 million individuals older than 12 years of age report
 current (past month) use of smokeless tobacco (ST). ST use has been associated with oral and
 extra-oral cancer as well as cardiovascular and cerebrovascular disease. To date, no
 pharmacotherapies have been shown to increase long-term (≥ 6 months) abstinence rates in ST
 users. Novel pharmacotherapies that decrease withdrawal symptoms and nicotine
 self-administration need to be tested in ST users. Varenicline (Chantix™, Pfizer) is a novel
 selective nicotinic receptor partial agonist with specificity for the α4β2 nicotine
 acetylcholine receptor that has demonstrated remarkable efficacy for increasing long-term
 tobacco abstinence rates in cigarette smokers. The novel mechanism of action of varenicline
 potentially circumvents the limitations of using nicotine replacement therapy or bupropion
 pharmacotherapy in ST users. The overall goal of this line of research is to develop
 effective pharmacologic treatments for ST users to increase long-term (≥ 6 months) abstinence
 rates. The central hypothesis of this application is that varenicline is efficacious for the
 treatment of ST users. To evaluate this hypothesis, we will conduct a pilot study to obtain
 preliminary estimates of efficacy of 12-weeks of varenicline for increasing the prolonged and
 point prevalence tobacco abstinence rates at 12 weeks (end-of-treatment) in ST users. We will
 also evaluate the effect of varenicline on nicotine withdrawal symptoms and tobacco craving.
 If the results are promising, we will plan for a multicenter, randomized, double-blinded,
 placebo-controlled clinical trial with the Oregon Research Institute in Eugene, OR, to
 investigate the efficacy of varenicline to increase long-term (≥ 6 months) abstinence rates
 in ST users.
Inclusion Criteria:

 Subjects will be eligible to participate if they:

 1. Are at least 18 years of age

 2. Have used ST daily for the past 12 months (regular user)

 3. Identify ST as their primary tobacco product

 4. Are in general good health (determined by medical history and screening physical
 examination)

 5. Has provided written informed consent to participate

 6. Are able to participate in all aspects of the study

 Exclusion Criteria:

 Individuals will be excluded from study participation if they:

 1. Are currently (in previous 30 days) using other behavioral or pharmacologic tobacco
 cessation programs (i.e., behavioral therapy, nicotine replacement therapy, clonidine,
 bupropion SR, or doxepin)

 2. Have self-reported current, untreated depression or a Beck Depression Inventory
 (BDI-II) Score of ≥ 20

 3. Have, as defined by the C-SSRS (Columbia-Suicide Severity Rating Scale);current
 non-specific suicidal thoughts, or have a lifetime history of a suicidal attempt
 (defined as "potentially self-injurious act committed with at least some wish to die,
 as a result of act.")

 4. History of psychosis or bipolar disorder

 5. Are currently pregnant or lactating or is of childbearing potential and not willing to
 use any form of contraception

 6. Have another member of their household already participating in this study

 7. Are allergic to varenicline

 8. Describe having a medical history of:

 -  Unstable angina

 -  Myocardial infarction within the past 3 months

 -  Cardiac dysrhythmia other than medication-controlled atrial fibrillation or PSVT

 -  Medically-treated or untreated hypertension with BP ≥ 200 systolic OR ≥ 100
 diastolic

 -  Have other medical or psychiatric conditions that would exclude the participant