Varenicline for the Treatment of Smokeless Tobacco

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Varenicline for the Treatment of Smokeless Tobacco Use

Conditions
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Nicotine Dependence

Intervention / Treatment
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* Drug: varenicline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects will be eligible to participate if they: Are at least 18 years of age Have used ST daily for the past 12 months (regular user) Identify ST as their primary tobacco product Are in general good health (determined by medical history and screening physical examination) Has provided written informed consent to participate Are able to participate in all aspects of the study Exclusion Criteria: Individuals will be excluded from study participation if they: 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) Have self-reported current, untreated depression or a Beck Depression Inventory (BDI-II) Score of ≥ 20 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.) History of psychosis or bipolar disorder Are currently pregnant or lactating or is of childbearing potential and not willing to use any form of contraception Have another member of their household already participating in this study Are allergic to varenicline 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: varenicline<br> | Drug: varenicline<br>* 12 weeks of varenicline 1 mg by mouth twice per day<br>* Other names: Chantix;|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* 12 weeks of placebo (double blinded) by mouth twice per day<br>* Other names: Chantix placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence All Tobacco Abstinence | 7-day point prevalence all tobacco abstinence at week 12 (end of treatment)confirmed by urine cotinine less than 50ng/ml | 12 weeks - end of treatment |