Tobacco Dependence
Conditions
Keywords
tobacco, nicotine, smoking, reward, reinforcement, craving, cues, conditioned stimuli, cue reactivity
Brief summary
The purpose of this study was to find out how varenicline works to help people quit smoking. Varenicline, also known as Chantix™, is an U.S. Food and Drug Administration (FDA) approved medication that has been shown to help people quit smoking. This study was trying to evaluate whether varenicline would change the response to smoking and the desire for cigarettes when compared to an inactive placebo control. This was not a quit smoking treatment study, and participants were not asked or required to stop smoking while in this study.
Detailed description
We proposed the following primary hypotheses: 1. Tonic (i.e., non-cue-provoked) craving levels would be lower in participants receiving varenicline versus placebo. 2. Cue-provoked cravings (self-report and physiological responding) would be lower in participants receiving varenicline versus placebo. (Secondary indices of craving include heart rate and skin conductance.) 3. The two primary indices of nicotine reward/reinforcement (mCEQ and choice index) would be lower in participants receiving varenicline versus placebo. (Secondary indices of nicotine reinforcement include smoking topography variables.) A final sample of 100 non-treatment seeking daily smokers were recruited from the Tampa-St. Petersburg-Clearwater Metropolitan Area via paid advertisements in, and press releases to, local newspapers, as well as targeted outdoor advertising via flyers (e.g., on public transportation). Following the screening session, participants were randomly assigned to receive either varenicline or placebo medication.
Interventions
DRUGvarenicline
Participants in this group received varenicline according to the schedule in the Arm Description.
DRUGplacebo
Participants in this group received a placebo and did not receive any active medication according to the schedule in the Arm Description.
Sponsors
Pfizer
H. Lee Moffitt Cancer Center and Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-60 years of age * Smoke at least 15 cigarettes daily * Expired-air carbon monoxide (CO) \> 10 ppm * Medically eligible to receive Varenicline.
Exclusion criteria
* Patients who are pregnant or lactating * Who show evidence of renal dysfunction (BUN \> 25 mg/dL, or creatinine \> 1.3 mg/dL) * Are using other smoking cessation medications * Have current psychiatric disorders (i.e. major depression, manic depression, and/or psychotic episodes) as determined by the Structured Clinical Interview for DSM Disorders (SCID) (First et al., 1996), will be excluded
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Tonic Craving Score (QSU) Based on Self Reports | 3 weeks per participant | Tonic Craving 1 (lowest) to 7 (highest). The Questionnaire of Smoking Urges (QSU), our primary measure of tonic craving, is a 32-item instrument, including 2 separate factor scales that roughly correspond to the desire to smoke for its pleasurable effects (positive reinforcement) or to remove unpleasant feelings of negative affect or withdrawal (negative reinforcement) (Tiffany and Drobes 1991). Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues. |
| Cue-provoked Cravings | 3 weeks per participant | Strength of Craving 0 (lowest) to 20 (highest). One item 0 - 20 Likert scale How strong was your craving to smoke a cigarette? |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smoking Topography - Number of Puffs on a Cigarette | 3 weeks per participant | \# Puffs = total number of puffs taken at Assessment Session. |
| A Measure of the Subjective Expected Value of a Cigarette | 3 weeks per participant | The cigarette choice procedure (Kidorf, Stitzer, and Griffiths, 1995) is a measure of the desire to smoke a cigarette. Participants are asked to hypothetically choose between smoking a cigarette now or receiving a small amount of money (from 10 cents up to $6 in increments of 10 cents). A crossover ($) value, at and above which participants prefer money, is obtained (Reid, Palmar, Raghavan, and Flammino, 2007). |
Countries
United States
Participant flow
Recruitment details
To achieve a sample size of 100 following attrition, we screened 573 smokers from the community and randomized 100 non-treatment seeking daily smokers to the two conditions. Smokers who were using other smoking cessation medications, or who had current mood or psychotic disorders were excluded.
Pre-assignment details
Participants completed a baseline evaluation including screening for inclusion and exclusion criteria, a medical evaluation, basic metabolic panel and pregnancy test for females. Participants who met all of the inclusion criteria were scheduled for the assessment sessions.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline For participants in the varenicline group, the medication doses followed the recommended dose schedule for the first 15 days of treatment: 0.5 mg once a day on days 1-3, 0.5 mg twice a day on days 4-7, and 1 mg twice a day on days 8-15. | 46 |
| Placebo Participants in this group received a placebo instead of medication. The placebo was taken once a day on days 1-3, twice a day on days 4-15. | 54 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 36 | 27 |
Baseline characteristics
| Characteristic | Varenicline | Placebo | 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 | 46 Participants | 54 Participants | 100 Participants |
| Region of Enrollment United States | 46 participants | 54 participants | 100 participants |
| Sex: Female, Male Female | 18 Participants | 21 Participants | 39 Participants |
| Sex: Female, Male Male | 28 Participants | 33 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 82 | 0 / 81 |
| serious Total, serious adverse events | 0 / 82 | 0 / 81 |
Outcome results
Primary
Cue-provoked Cravings
Strength of Craving 0 (lowest) to 20 (highest). One item 0 - 20 Likert scale How strong was your craving to smoke a cigarette?
Time frame: 3 weeks per participant
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Cue-provoked Cravings | 11.18 Scores on a scale | Standard Error 0.76 |
| Placebo | Cue-provoked Cravings | 14.61 Scores on a scale | Standard Error 0.69 |
Primary
Tonic Craving Score (QSU) Based on Self Reports
Tonic Craving 1 (lowest) to 7 (highest). The Questionnaire of Smoking Urges (QSU), our primary measure of tonic craving, is a 32-item instrument, including 2 separate factor scales that roughly correspond to the desire to smoke for its pleasurable effects (positive reinforcement) or to remove unpleasant feelings of negative affect or withdrawal (negative reinforcement) (Tiffany and Drobes 1991). Following overnight abstinence, each session included assessment of tonic craving, reactivity (including craving) to smoking cues.
Time frame: 3 weeks per participant
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Tonic Craving Score (QSU) Based on Self Reports | 3.53 Scores on a scale | Standard Error 0.21 |
| Placebo | Tonic Craving Score (QSU) Based on Self Reports | 4.93 Scores on a scale | Standard Error 0.19 |
Secondary
A Measure of the Subjective Expected Value of a Cigarette
The cigarette choice procedure (Kidorf, Stitzer, and Griffiths, 1995) is a measure of the desire to smoke a cigarette. Participants are asked to hypothetically choose between smoking a cigarette now or receiving a small amount of money (from 10 cents up to $6 in increments of 10 cents). A crossover ($) value, at and above which participants prefer money, is obtained (Reid, Palmar, Raghavan, and Flammino, 2007).
Time frame: 3 weeks per participant
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | A Measure of the Subjective Expected Value of a Cigarette | 2.46 Dollars | Standard Error 0.3 |
| Placebo | A Measure of the Subjective Expected Value of a Cigarette | 3.72 Dollars | Standard Error 0.28 |
Secondary
Smoking Topography - Number of Puffs on a Cigarette
\# Puffs = total number of puffs taken at Assessment Session.
Time frame: 3 weeks per participant
Population: Per Protocol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Smoking Topography - Number of Puffs on a Cigarette | 6.05 Puffs on a Cigarette | Standard Error 0.77 |
| Placebo | Smoking Topography - Number of Puffs on a Cigarette | 9.86 Puffs on a Cigarette | Standard Error 0.76 |