Cigarette Smoking
Conditions
Brief summary
The goal of this study is to evaluate the effects of varenicline versus nicotine replacement versus placebo on personal smoking environment cue (PSE) reactivity. The results of this study will inform whether first-line pharmacotherapies for nicotine dependence (e.g. nicotine patch, varenicline) alter reactivity to environment cues. The investigators propose to identify 120 regular cigarette smokers who will complete 10 visits (1 screening visit, 1 training visit, 1 camera turn-in 2 cue exposure sessions and 4 post-quit medication check sessions). Smokers will be randomized to one of three medication conditions: placebo (PLAC; n=40), transdermal nicotine patch (NRT; n=40) or varenicline (VAR; n=40) in a double blind, double-dummy design. Reactivity variables (craving, latency to smoke, and smoke intake) will be entered into 3 (Medication: NRT, VAR, PLAC) x 2 (Environment: smoking, nonsmoking) repeated measures ANOVAs with random-effects. The investigators hypothesize that personal smoking, as compared to nonsmoking environments, will be associated with greater reactivity (i.e. increased craving and smoke intake; decreased latency to smoke). A Medication x Environment interaction will be characterized by decreased reactivity to smoking as compared to nonsmoking environments in the VAR and NRT groups as compared to the PLAC group.
Interventions
DRUGNicotine Patch
Participants will wear 21mg/day patches for days 1-14. After day 14, participants will make a quit attempt continue to wear the 21mg/d patches for 6 weeks, then step down to 14mg/d patches for 2 weeks and finally step down 7mg/d for the last 2 weeks of treatment. Participants will also take a placebo capsule. During days 8-14, participants will undergo 2 cue-exposure sessions.
DRUGVarenicline
Varenicline (VAR) will be administered by titrating to steady state levels over a 7 day induction period (.5 mg once daily in Days 1-3; .5 mg twice daily on Days 4-7 and 1 mg twice daily on Days 8-14). Participants will continue on 1mg twice daily until the end of treatment (days 15-84). Participants will also wear a placebo patch. During days 8-14, participants will undergo 2 cue-exposure sessions.
In the PLAC group, participants will receive placebo patches and placebo capsules for 14 days prior to quitting smoking. They will then switch to wearing a nicotine patch the morning of their quit day in order to provide them with the minimum standard of care. During days 8-14, participants will undergo 2 cue-exposure sessions. In the VAR group, participants will wear a placebo patch while taking varenicline.
DRUGPlacebo Capsule
In the PLAC group, participants will receive placebo patches and placebo capsules for 14 days prior to quitting smoking. They will then switch to wearing a nicotine patch the morning of their quit day in order to provide them with the minimum standard of care. During days 8-14, participants will undergo 2 cue-exposure sessions. In the NRT group, participants will take a placebo capsule while wearing nicotine patches.
Sponsors
National Institutes of Health (NIH)
National Institute on Drug Abuse (NIDA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. generally healthy \[(i.e. ambulatory, not currently sick)\] 2. between the ages of 18 and 60 3. smoking of at least 5 cig/day of a brand delivering ≥ 0.5 mg nicotine (FTC method) for \> 1 year 4. an expired CO concentration of at least 10 ppm (to confirm inhalation) or urinary cotinine \>1000 ng/mL (NicAlert = 6). 5. interest in quitting smoking within the timeframe of the experiment. 6. ability to identify 4 personal smoking and 4 personal non-smoking places.
Exclusion criteria
1. immediate or no desire to quit smoking; 2. inability to attend all required experimental sessions; 3. use of psychoactive medications; 4. use of smokeless tobacco including e-cigarettes in the past 30 days; 5. current alcohol or drug abuse; 6. use of illegal drugs as measured by urine drug screen (excluding marijuana); 7. use of experimental (investigational) drugs; 8. current use of nicotine replacement therapy or other smoking cessation treatment; 9. Hypertension (systolic \>140 mm Hg, diastolic \>100 mm Hg, coupled with a history of hypertension); subjects with no previous diagnosis of hypertension may have a screening blood pressure up to 160/100. Participants with a history of hypertension may, however, be allowed to participate in the study if the study physician determines that the condition is stable, controlled by medication, and in no way jeopardizes the individual's safety; 10. Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg); 11. Coronary heart disease; 12. Lifetime history of heart attack; 13. Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure, arrhythmia); Abnormal EKG results suggestive of ischemia or undiagnosed cardiovascular disease please consider adding if it seems reasonable. For example, ST-segment depression or elevation, T-wave abnormalities, and lack of R wave are obtained with a 12-lead EKG). 14. Active skin disorder (e.g., psoriasis) within the last year, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds); 15. Medical condition that may contraindicate participation in the opinion of the investigator and study physician.(for example, EKG results) 16. Current psychiatric disease (with the exception of anxiety disorders, OCD and ADHD); 17. Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide; 18. Current depression - The Prime-MD will be used to screen for current (within 2 weeks) depression. Potential subjects who score \>9 (or who score \>0 on item #9 (Thoughts that you would be better off dead, or of hurting yourself in some way) will be excluded from study participation, and, at the discretion of the study physician, referred to appropriate psychiatric treatment; 19. Bulimia or anorexia; 20. Significant adverse reaction to Chantix/Varenicline in the past; 21. Currently pregnant, breast feeding or likely to become pregnant; 22. History of seizure disorder. 23. A quit attempt within the last 30 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Craving Score During Cue Exposure Task | Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3) | Scores range from 0 (no craving) to 100 (extreme craving). |
| Change in Latency to Smoke During Cue Exposure Task | Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3) | The latency is the interval between smoking one cigarette and wanting, craving, or needing another. |
| Change in Smoke Intake During Cue Exposure Task | Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3) | Measured by number of puffs. |
Countries
United States
Participant flow
Pre-assignment details
37 participants were withdrawn from the study prior to treatment assignment due to either loss of interest, lost to contact, or inability to complete baseline procedures per protocol.
Participants by arm
| Arm | Count |
|---|---|
| Placebo (PLAC) Placebo Nicotine Patch: Participants will wear 21mg/day patches for days 1-14. After day 14, participants will make a quit attempt, continue to wear the 21mg patches for 6 weeks, then step down to 14mg patches for 2 weeks and finally step down 7mg/d for the last 2 weeks of treatment. Participants will also take a placebo capsule. During days 8-14, participants will undergo 2 cue-exposure sessions.
In the PLAC group, participants will receive placebo patches and placebo capsules for 14 days prior to quitting smoking. They will then switch to wearing a nicotine patch the morning of their quit day in order to provide them with the minimum standard of care. During days 8-14, participants will undergo 2 cue-exposure sessions. | 31 |
| Transdermal Nicotine Patch (NRT) Nicotine Patch: Participants will wear 21mg/day patches for days 1-14. After day 14, participants will make a quit attempt continue to wear the 21mg/d patches for 6 weeks, then step down to 14mg/d patches for 2 weeks and finally step down 7mg/d for the last 2 weeks of treatment. Participants will also take a placebo capsule. During days 8-14, participants will undergo 2 cue-exposure sessions.
In the NRT group, participants will take a placebo capsule while wearing nicotine patches. | 27 |
| Varenicline (VAR) Varenicline: Varenicline (VAR) will be administered by titrating to steady state levels over a 7 day induction period (.5 mg once daily in Days 1-3; .5 mg twice daily on Days 4-7 and 1 mg twice daily on Days 8-14). Participants will continue on 1mg twice daily until the end of treatment (days 15-84). Participants will also wear a placebo patch. During days 8-14, participants will undergo 2 cue-exposure sessions.
In the VAR group, participants will wear a placebo patch while taking varenicline. | 30 |
| Total | 88 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 1 | 4 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo (PLAC) | Total | Varenicline (VAR) | Transdermal Nicotine Patch (NRT) |
|---|---|---|---|---|
| Age, Continuous | 46.6 years STANDARD_DEVIATION 11.6 | 44.4 years STANDARD_DEVIATION 12.3 | 41.2 years STANDARD_DEVIATION 11.9 | 47.4 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 29 Participants | 28 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 57 Participants | 2 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants | 45 Participants | 14 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 16 Participants | 39 Participants | 14 Participants | 9 Participants |
| Region of Enrollment United States | 31 Participants | 88 Participants | 30 Participants | 27 Participants |
| Sex: Female, Male Female | 17 Participants | 44 Participants | 15 Participants | 12 Participants |
| Sex: Female, Male Male | 14 Participants | 44 Participants | 15 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 27 | 0 / 30 |
| other Total, other adverse events | 0 / 31 | 0 / 27 | 0 / 30 |
| serious Total, serious adverse events | 2 / 31 | 0 / 27 | 0 / 30 |
Outcome results
Primary
Change in Craving Score During Cue Exposure Task
Scores range from 0 (no craving) to 100 (extreme craving).
Time frame: Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3)
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PLAC) | Change in Craving Score During Cue Exposure Task | -11.17 score on a scale | Standard Deviation 24.93 |
| Transdermal Nicotine Patch (NRT) | Change in Craving Score During Cue Exposure Task | -8.84 score on a scale | Standard Deviation 28.3 |
| Varenicline (VAR) | Change in Craving Score During Cue Exposure Task | -14.29 score on a scale | Standard Deviation 25.09 |
p-value: 0.534ANOVA
Primary
Change in Latency to Smoke During Cue Exposure Task
The latency is the interval between smoking one cigarette and wanting, craving, or needing another.
Time frame: Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3)
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PLAC) | Change in Latency to Smoke During Cue Exposure Task | 30.22 seconds | Standard Deviation 71.58 |
| Transdermal Nicotine Patch (NRT) | Change in Latency to Smoke During Cue Exposure Task | 48.04 seconds | Standard Deviation 95.79 |
| Varenicline (VAR) | Change in Latency to Smoke During Cue Exposure Task | 65.15 seconds | Standard Deviation 133.12 |
p-value: 0.26ANOVA
Primary
Change in Smoke Intake During Cue Exposure Task
Measured by number of puffs.
Time frame: Cue Exposure 1 (beginning of week 3) to Cue Exposure 2 (end of week 3)
Population: Subjects who completed the study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo (PLAC) | Change in Smoke Intake During Cue Exposure Task | 14.42 puffs | Standard Deviation 6.35 |
| Transdermal Nicotine Patch (NRT) | Change in Smoke Intake During Cue Exposure Task | 12.21 puffs | Standard Deviation 4.42 |
| Varenicline (VAR) | Change in Smoke Intake During Cue Exposure Task | 12.98 puffs | Standard Deviation 7.9 |
p-value: 0.318ANCOVA