Nicotine Dependence
Conditions
Keywords
Nicotine addiction, Cigarette smoking, Smoking cessation, Zyban, Chantix, Nicotine patches, varenicline, bupropion, fMRI
Brief summary
The purpose of this study is to look at brain function in order to understand how different treatments work to help people quit smoking. In this study, the investigators will look at the effects of nicotine patches, Chantix alone or Chantix paired with Zyban.
Interventions
DRUGVarenicline
DRUGBupropion
DRUGNicotine patches
OTHERPlacebo varenicline
OTHERPlacebo bupropion
OTHERPlacebo patch
Sponsors
National Institute on Drug Abuse (NIDA)
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
* Are generally healthy; * Are 18-50 years old; * Smoke an average of at least 10 cigarettes per day for at least three cumulative years; * Have an afternoon expired air carbon monoxide (CO) reading of at least 10ppm; * Are right-handed as measured by a two-item scale used in our laboratory; * Express a desire to quit smoking in the next thirty days. * Potential subjects must agree to use acceptable contraception during their participation in this study. Potential subjects must agree to avoid the following during their participation in this study: * participation in any other nicotine-related modification strategy outside of this protocol; * use of tobacco products other than cigarettes, including pipe tobacco, cigars, e-cigarettes, snuff, and chewing tobacco; * use of experimental (investigational) drugs or devices; * use of illegal drugs; * use of opiate medications.
Exclusion criteria
* Inability to attend all required experimental sessions; * Presence of conditions that would make MRI unsafe (e.g. pacemaker); * 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. * Hypotension with symptoms (systolic \<90 mm Hg, diastolic \<60 mm Hg). * Coronary heart disease; * Lifetime history of heart attack; * Cardiac rhythm disorder (irregular heart rhythm); * Chest pains (unless history, exam, and ECG clearly indicate a non-cardiac source); * Cardiac (heart) disorder (including but not limited to valvular heart disease, heart murmur, heart failure); * History of skin allergy; * Active skin disorder (e.g., psoriasis) within the last five years, except minor skin conditions (including but not limited to facial acne, minor localized infections, and superficial minor wounds); * Liver or kidney disorder (except kidney stones, gallstones); * Gastrointestinal problems or disease other than gastroesophageal reflux or heartburn; * Active ulcers in the past 30 days; * Lung disorder (including but not limited to Chronic obstructive pulmonary disease (COPD), emphysema, and asthma); * Brain abnormality (including but not limited to stroke, brain tumor, and seizure disorder); * Migraine headaches that occur more frequently than once per week; * Recent, unexplained fainting spells; * Problems giving blood samples; * Diabetes; * Current cancer or treatment for cancer in the past six months (except basal or squamous cell skin cancer); * Other major medical condition; * Current psychiatric disease (with the exception of anxiety disorders, Obsessive-compulsive disorder (OCD) and Attention deficit hyperactivity disorder (ADHD)); * Bulimia or anorexia; * Suicidal ideation (within the past 10 years) or lifetime occurrence of attempted suicide; * Current depression; * Pregnant or nursing mothers; * Alcohol abuse; * Significant adverse reaction to nicotine patch, bupropion/Wellbutrin/Zyban or Chantix/Varenicline in the past. * Use (within the past 30 days) of: * Illegal drugs (or if the urine drug screen is positive); * Experimental (investigational) drugs; * Psychiatric medications including antidepressants, anti-psychotics or any other medications that are known to affect smoking cessation (e.g. clonidine); * Smokeless tobacco (chewing tobacco, snuff), cigars or pipes; * Nicotine replacement therapy or any other smoking cessation aid. * Use (within the past 14 days) of: * Opiate medications for pain or sleep (non-opiate medication for pain or sleep will be allowed).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment | Mean blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) cue-reactivity signal following 2 week pre-quit treatment, controlling for baseline cue-reactivity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Days to First Cigarette Following Quitting Smoking | Up to 11 weeks post quit day. | Days to first cigarette (i.e. lapse) will be measured via self-report. |
Countries
United States
Participant flow
Pre-assignment details
Of the 282 participants who were consented and screened, 191 were screen fails, 2 withdrew voluntarily before being assigned to a study arm, and 13 were lost to contact between screening and the first study visit. Therefore, only 76 participants were randomized and started the study.
Participants by arm
| Arm | Count |
|---|---|
| Varenicline For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week. Subsequently, the dose will be 1 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline, smokers in this group will also receive placebo bupropion and placebo patches.
Varenicline
Nicotine patches
Placebo bupropion
Placebo patch | 18 |
| NRT (Nicotine Patches Only) 21 mg/24 h for 2 weeks before the quit date and 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.
Nicotine patches
Placebo varenicline
Placebo bupropion | 19 |
| Varenicline + Bupropion For the first 3 days after being switched from Nicotine Replacement Therapy (NRT) occurring at one week before the target quit date, smokers in this group will receive varenicline at a dose of 0.5 mg once per day followed by 0.5 mg twice a day for the remaining 4 days of that week plus bupropion at a dose of 150mg once per day. Subsequently, the dose of varenicline will be 1 mg twice per day and the dose of bupropion will be 150 mg twice per day, and will remain at that dose for the remainder of the 12 weeks. During the time they receive varenicline and bupropion, smokers in this group will also receive placebo patches.
Varenicline
Bupropion
Nicotine patches
Placebo patch | 20 |
| Post-quit NRT Nicotine patches at 21 mg/24 h for 7 weeks after the quit date, 14 mg/24 h for 2 weeks, and 7 mg/ 24 h for 2 weeks. After the 1st week, smokers in this group will also receive placebo bupropion and placebo varenicline.
Nicotine patches
Placebo varenicline
Placebo bupropion
Placebo patch | 19 |
| Total | 76 |
Baseline characteristics
| Characteristic | Varenicline | NRT (Nicotine Patches Only) | Varenicline + Bupropion | Post-quit NRT | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants | 18 Participants | 20 Participants | 19 Participants | 75 Participants |
| Age, Continuous | 37.56 years STANDARD_DEVIATION 10.68 | 41.89 years STANDARD_DEVIATION 12.22 | 38.35 years STANDARD_DEVIATION 11.42 | 37.16 years STANDARD_DEVIATION 10.59 | 38.75 years STANDARD_DEVIATION 11.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 1 Participants | 2 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 16 Participants | 18 Participants | 18 Participants | 19 Participants | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 6 Participants | 9 Participants | 7 Participants | 34 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 11 Participants | 10 Participants | 12 Participants | 38 Participants |
| Region of Enrollment United States | 18 participants | 19 participants | 20 participants | 19 participants | 76 participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 8 Participants | 10 Participants | 40 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 12 Participants | 9 Participants | 36 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 18 | 6 / 19 | 6 / 20 | 4 / 19 |
| serious Total, serious adverse events | 0 / 18 | 0 / 19 | 0 / 20 | 0 / 19 |
Outcome results
Primary
The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences
Mean blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) cue-reactivity signal following 2 week pre-quit treatment, controlling for baseline cue-reactivity.
Time frame: change from baseline in whole brain blood-oxygen-level dependent (BOLD) contrast sensitive functional magnetic resonance imaging (fMRI) images collected during a cue-reactivity task following 2 weeks of pre-quit treatment
Population: Only participants who completed both scanning sessions and provided useable data were included in imaging analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left amygdala | 0.057 percent BOLD signal change | Standard Deviation 0.285 |
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right amydala | .051 percent BOLD signal change | Standard Deviation 0.337 |
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left anterior insula | .094 percent BOLD signal change | Standard Deviation 0.196 |
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right anterior insula | -.008 percent BOLD signal change | Standard Deviation 0.224 |
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left medial prefrontal cortex | .129 percent BOLD signal change | Standard Deviation 0.162 |
| Varenicline | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right medial prefrtonal cortex | .058 percent BOLD signal change | Standard Deviation 0.171 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right medial prefrtonal cortex | -.010 percent BOLD signal change | Standard Deviation 0.277 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right anterior insula | .065 percent BOLD signal change | Standard Deviation 0.305 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left amygdala | .007 percent BOLD signal change | Standard Deviation 0.186 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left anterior insula | .013 percent BOLD signal change | Standard Deviation 0.244 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right amydala | -.014 percent BOLD signal change | Standard Deviation 0.19 |
| NRT (Nicotine Patches Only) | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left medial prefrontal cortex | .026 percent BOLD signal change | Standard Deviation 0.294 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right amydala | .134 percent BOLD signal change | Standard Deviation 0.266 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left anterior insula | -.015 percent BOLD signal change | Standard Deviation 0.16 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right anterior insula | .019 percent BOLD signal change | Standard Deviation 0.188 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right medial prefrtonal cortex | -.176 percent BOLD signal change | Standard Deviation 0.641 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left medial prefrontal cortex | -.120 percent BOLD signal change | Standard Deviation 0.562 |
| Varenicline + Bupropion | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left amygdala | .160 percent BOLD signal change | Standard Deviation 0.258 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left medial prefrontal cortex | .009 percent BOLD signal change | Standard Deviation 0.2 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right medial prefrtonal cortex | -.017 percent BOLD signal change | Standard Deviation 0.178 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right amydala | .020 percent BOLD signal change | Standard Deviation 0.249 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | right anterior insula | .082 percent BOLD signal change | Standard Deviation 0.333 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left amygdala | .129 percent BOLD signal change | Standard Deviation 0.278 |
| Post-quit NRT | The Amygdala, Anterior Insula, and Medial Prefrontal Cortex Scans Will be Compared to Evaluate Significant Differences | left anterior insula | .179 percent BOLD signal change | Standard Deviation 0.288 |
Secondary
Days to First Cigarette Following Quitting Smoking
Days to first cigarette (i.e. lapse) will be measured via self-report.
Time frame: Up to 11 weeks post quit day.
Population: Twenty-eight subjects dropped from the study prior to their scheduled quit day, so they were not included in these analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Varenicline | Days to First Cigarette Following Quitting Smoking | 9.15 days | Standard Deviation 22.143 |
| NRT (Nicotine Patches Only) | Days to First Cigarette Following Quitting Smoking | 15.21 days | Standard Deviation 26.066 |
| Varenicline + Bupropion | Days to First Cigarette Following Quitting Smoking | 9.90 days | Standard Deviation 23.96 |
| Post-quit NRT | Days to First Cigarette Following Quitting Smoking | 5.73 days | Standard Deviation 18.666 |