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
This study includes a screening period in which you will be informed of the study; if you decide to participate you will be asked to sign this study informed consent form. Afterwards you will be asked to undergo a series of screening tests to see if you are eligible to participate in this study. The tests will include questions concerning your medical and smoking history, a brief physical exam, diagnostic tests to determine your nicotine dependence, as well as a pregnancy test using a urine sample. After that you will be randomized (as in the flip of a coin) to one of two groups: varenicline 1-mg by mouth twice per day or a matching placebo (inactive drug). You will stay on your assigned dose for 12 weeks with weekly or biweekly clinic visits (weeks 1-4,6,8,10 and 12). While on the study medication, you will be called for a brief phone visit on the weeks that you do not come in for a clinic visit (weeks 5,7,9,and 11). When you complete your 12 weeks of study drug; you will return after two weeks (week 14) and then be asked to return for a final study visit (week 24). Everyone in study will also receive nicotine dependence counseling.
You will be in the study for 6 months.
Last updated: 07/10/2012
NCT ID: NCT00813917
IRB Number:08-005359
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