Nicotine Dependence
Conditions
Keywords
Tobacco, nicotine, smoking, varenicline, human laboratory study, stress tolerance, startle response, cognitive assessment, progressive ratio
Brief summary
The purpose of this study is to test the ways that a drug called varenicline helps smokers to quit smoking. Varenicline is also called Chantix® and is approved by the United States Food and Drug Administration (FDA) to help people quit smoking. We will test how varenicline works by having you quit smoking and complete tasks that assess how you think and feel. We predict that varenicline help reduce anxiety, improve attention and concentration, and reduce how satisfying cigarettes are.
Detailed description
The purpose of this study is to understand the therapeutic mechanisms of varenicline, a novel nicotinic analogue, through focused measures of potential psychological and physiological mediators. Varenicline is an FDA-approved pharmacotherapy for smoking cessation that is believed to provide relief from craving and withdrawal through agonism and antagonism of some central nervous system nicotinic acetylcholinergic receptors. However, no controlled studies have established the physiological and psychological processes that mediate the efficacy of varenicline in humans. The main goal of the proposed pilot study is to evaluate and compare the effects of varenicline on subjective, cognitive, and physiological outcomes, using a randomized, placebo-controlled, double-blind between-groups design. The study will combine both brief clinical trial methodology with human laboratory approaches. A secondary goal is to validate the utility of the laboratory paradigms for the identification of future smoking cessation agents.
Interventions
DRUGPlacebo
Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.).
DRUGVarenicline
Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.).
Sponsors
National Institute on Drug Abuse (NIDA)
Pfizer
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1.1. Who. Subjects will be women and men between the ages of 18 and 40 who have smoked at least 10 cigarettes per day for at least 1 year. They will respond to requests in the public media for individuals who are interested in quitting smoking. 1.2. Total sample/Number per group. The total randomized sample size will equal 20 subjects, equally distributed across the two medication groups. 1.3. Inclusion Criteria. 1. 18 years to 60 years. 2. Smoke Marlboro Lights (This criterion was selected to reduce inter-subject variation in response variables as has been done in many human laboratory studies of smoking behavior. Over 40% of all smokers smoke some type of the Marlboro brand of cigarette (Substance Abuse and Mental Health Services Administration, 2005). Based on telephone screen data for 767 subjects collected at TURC, Marlboro Light cigarettes are the most common type of Marlboro smoked in our sampling population (158/252 Marlboro users \[63%\]). Therefore, we have decided to only enroll those smoking Marlboro Light cigarettes, non-menthol). 3. Smoked at least 10 cigarettes/day for at least 1 year. 4. English speaking and reading. 5. Females who are of childbearing potential must practice effective contraception and meet the following criteria: 1. Are instructed to avoid pregnancy through 30 days after the last dose of study medication. 2. Have a negative urine pregnancy test at baseline. 3. Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication. 6. Willingness to not use illicit drugs during study period including marijuana.
Exclusion criteria
1. Concurrent use of tobacco products (other than cigarettes) or nicotine products. 2. Medications that might affect the outcome measures of nicotine reward, cognition, anxiety, and stress will also be a basis for exclusion. These medications include psychotropic drugs (i.e., anti-psychotic, anti-depressant, anti-anxiety, or stimulant), anti- hypertensive agents (e.g., beta-blockers), and other drugs that can influence the outcome domains. 3. History of kidney disease or renal impairment since varenicline is primarily excreted by the kidney and thus such patients are vulnerable to increased and potentially toxic levels of varenicline. 4. Treatment for drug or alcohol dependence during the last year, or evidence of alcohol abuse so severe that the patient is judged potentially unable to comply with the protocol. 5. Suicidal or homicidal ideation. 6. History of bipolar disorder, schizophrenia, schizoaffective disorder, attention deficit disorder, or attention deficit hyperactivity disorder. 7. Current major depression or anxiety disorder. 8. Pregnant or lactating or planning pregnancy during treatment period. 9. Having plans to leave the immediate geographical area within 2 months. 10. Unwillingness or inability to give written informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Withdrawal Scale | 21 days | Scale is equal to days subject did not smoke Scale is 0-5 0 being no days 5 being did not quit at all |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Varenicline Placebo Varenicline
Placebo: Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.). | 4 |
| Varenicline Varenicline
Varenicline: Days 1 - 3 (0.5 mg tablet, q.d.), Days 4 - 7 (0.5 mg tablet, b.i.d.), and Day 8 - 21 (1 mg tablet, b.i.d.). | 3 |
| Total | 7 |
Baseline characteristics
| Characteristic | Varenicline | Placebo Varenicline | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 4 Participants | 7 Participants |
| Age, Continuous | 38.3 years STANDARD_DEVIATION 9.7 | 27.3 years STANDARD_DEVIATION 5.69 | 32.0 years STANDARD_DEVIATION 9.1 |
| Region of Enrollment United States | 3 participants | 4 participants | 7 participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 4 | 0 / 3 |
| serious Total, serious adverse events | 0 / 4 | 0 / 3 |
Outcome results
Primary
Nicotine Withdrawal Scale
Scale is equal to days subject did not smoke Scale is 0-5 0 being no days 5 being did not quit at all
Time frame: 21 days
Population: Treatment-seeking smokers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo Varenicline | Nicotine Withdrawal Scale | 3.3 units on a scale | Standard Deviation 5.3 |
| Varenicline | Nicotine Withdrawal Scale | 0.3 units on a scale | Standard Deviation 3.8 |