Nicotine Dependence
Conditions
Keywords
Varenicline, Imaging, fMRI
Brief summary
This project aims to define mechanisms through which varenicline might be an effective smoking cessation medication.
Detailed description
Thirty treatment seeking smokers will be recruited to complete a 40-day within-subject (cross-over), double-blind study that will assess effects of varenicline on brain activation while performing certain tasks. Prior to beginning the study, participants will complete an health and physical screening to determine final eligibility. Following a medication run-up and a 3.5 day abstinence period, participants will complete study period 1 (an fMRI scan while performing attention, working memory and emotion tasks). After a 14 to 21-day washout period the study procedures will be repeated with placebo (order of study medication counterbalanced). After completion of both study periods, all participants will be offered a 13-week quit smoking program with varenicline.
Interventions
DRUGVarenicline
Day 1 - Day 3 0.5mg once daily Day 4 - Day 7 0.5mg twice daily Day 8 - Day 13 1.0mg twice daily
DRUGPlacebo
Participants will take placebo pills for 13 days using the same regimen as the varenicline study period.
Sponsors
Pfizer
National Cancer Institute (NCI)
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Treatment-seeking smokers between the ages of 18 and 65, that smoke at least 10 cigarettes/day for at least the past 6 months 2. Provide a baseline CO (carbon monoxide) reading of \>10ppm 3. Provide written informed consent and are fluent, English-speaking 4. Weight of equal to or less than 300 lbs
Exclusion criteria
Smoking Behavior 1. Use of chewing tobacco, snuff or cigars 2. Current enrollment or plans to enroll in another smoking cessation program in the next 5 months 3. Plan to use other nicotine substitutes or smoking cessation treatments in the next 5 months 4. Provide a baseline CO (carbon monoxide) reading ≤10 ppm Alcohol/Drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change BOLD Signal | Day 13 | We calculated the percent BOLD signal change while performing the N-back task between the varenicline vs. placebo session. We subtracted BOLD signal observed during the 0-back condition from the BOLD signal observed during the 3-back condition (3back minus 0-back)We controlled for relevant co-variates such as sex, nicotine dependence level and education. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) | Day 13 | We examined the difference in correct reaction time on the N-back task between varenicline and placebo treatment. Models included terms for the main effect of treatment period (varenicline vs. placebo), memory load (0-back, 1-back, 2-back, 3-back) and covariates. We tested for interactions between nicotine dependence severity and treatment. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from mass media advertising in the greater Philadelphia area from November 2007 - June 2008.
Pre-assignment details
All participants completed a 14 day wash-out period between the two study phases. They were instructed to resume their usual smoking behavior in this wash-out phase.
Participants by arm
| Arm | Count |
|---|---|
| Placebo First, Then Varenicline Days 1 - 3: 0.5 mg once a day orally Days 4 - 7: 0.5 mg twice a day orally Days 8 - 13: 1 mg twice a day orally | 19 |
| Varenicline First, Then Placebo Days 1 - 3: 0.5 mg once a day orally Days 4 - 7: 0.5 mg twice a day orally Days 8 - 13: 1 mg twice a day orally | 19 |
| Total | 38 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: 13 Days | Claustrophobia | 0 | 1 |
| Period 1: 13 Days | MRI scanner technical issue | 1 | 0 |
| Period 1: 13 Days | Protocol Violation | 2 | 4 |
| Period 1: 13 Days | Time | 1 | 0 |
| Period 2: 14 Days | Protocol Violation | 0 | 2 |
| Period 3: 13 Days | MRI data quality | 2 | 2 |
| Period 3: 13 Days | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Varenicline First, Then Placebo | Placebo First, Then 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 | 19 Participants | 19 Participants | 38 Participants |
| Age Continuous | 39.79 years STANDARD_DEVIATION 12.68 | 41.05 years STANDARD_DEVIATION 13.32 | 40.42 years STANDARD_DEVIATION 12.84 |
| Region of Enrollment United States | 19 participants | 19 participants | 38 participants |
| Sex: Female, Male Female | 10 Participants | 9 Participants | 19 Participants |
| Sex: Female, Male Male | 9 Participants | 10 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 19 | 1 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Percent Change BOLD Signal
We calculated the percent BOLD signal change while performing the N-back task between the varenicline vs. placebo session. We subtracted BOLD signal observed during the 0-back condition from the BOLD signal observed during the 3-back condition (3back minus 0-back)We controlled for relevant co-variates such as sex, nicotine dependence level and education.
Time frame: Day 13
Population: Participants who completed both study phases were included in the analyses (n=25). Additional participants (n=3) were excluded due to measurement artifact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percent Change BOLD Signal | 0.48 BOLD Signal Change (3-back minus 0-back) | Standard Error 0.05 |
| Varenicline | Percent Change BOLD Signal | 0.61 BOLD Signal Change (3-back minus 0-back) | Standard Error 0.03 |
Secondary
Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time)
We examined the difference in correct reaction time on the N-back task between varenicline and placebo treatment. Models included terms for the main effect of treatment period (varenicline vs. placebo), memory load (0-back, 1-back, 2-back, 3-back) and covariates. We tested for interactions between nicotine dependence severity and treatment.
Time frame: Day 13
Population: Participants who completed both study phases were included in the analysis. Other participants (n=3) were excluded due to measurement artifact.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) | 692.14 Milliseconds | Standard Deviation 128.57 |
| Varenicline | Effect of Varenicline Treatment on Task Performance (N-back Correct Response Time) | 637.99 Milliseconds | Standard Deviation 164.3 |