Nicotine Dependence
Conditions
Brief summary
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
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.
Interventions
DRUGvarenicline
12 weeks of varenicline 1 mg by mouth twice per day
DRUGplacebo
12 weeks of placebo (double blinded) by mouth twice per day
Sponsors
National Institutes of Health (NIH)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 7-day Point Prevalence All Tobacco Abstinence | 12 weeks - end of treatment | 7-day point prevalence all tobacco abstinence at week 12 (end of treatment)confirmed by urine cotinine less than 50ng/ml |
Countries
United States
Participant flow
Recruitment details
Recruitment began on 4/13/09 and completed on 08/16/10. Interested subjects who passed a phone pre-screen were seen at a medical clinic (Mayo Clinic in Rochester, MN and Franciscan Skemp Medical Center in Lacrosse, WI) for consenting and additional study procedures to determine eligibility.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline varenicline-1mg/day for 12 weeks | 38 |
| Placebo nonactive lookalike pill per day for 12 weeks | 38 |
| Total | 76 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 1 |
| Overall Study | Withdrawal by Subject | 3 | 4 |
Baseline characteristics
| Characteristic | Placebo | Varenicline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 0 Participants | 2 Participants |
| Age, Categorical Between 18 and 65 years | 36 Participants | 38 Participants | 74 Participants |
| Age Continuous | 40.7 years STANDARD_DEVIATION 10.1 | 41.0 years STANDARD_DEVIATION 12.4 | 40.9 years STANDARD_DEVIATION 11.2 |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 38 Participants | 38 Participants | 76 Participants |
| smokeless tobacco quantity | 3.2 cans per week STANDARD_DEVIATION 2 | 4.0 cans per week STANDARD_DEVIATION 3.5 | 3.6 cans per week STANDARD_DEVIATION 2.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 15 / 38 | 5 / 38 |
| serious Total, serious adverse events | 0 / 38 | 0 / 38 |
Outcome results
Primary
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
Time frame: 12 weeks - end of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Varenicline | 7-day Point Prevalence All Tobacco Abstinence | 21 participants |
| Placebo | 7-day Point Prevalence All Tobacco Abstinence | 16 participants |
Comparison: Data were compared between treatment groups using Chi Square test.p-value: 0.126Chi-squared