Smoking
Conditions
Brief summary
The goal of this study is to evaluate the effects of a smoking cessation intervention combining behavioral treatment with low nicotine cigarettes on neuroimaging measures of reward function and smoking cessation outcomes. The results of this study will provide information about mechanisms contributing to smoking and smoking cessation and will help to guide future treatment studies.
Detailed description
Smokers who are interested in quitting will be randomly assigned to one of two treatment conditions. In the BA +VLNC condition (n = 16) smokers will switch to smoking very low nicotine cigarettes (VLNCs) while wearing a 21 mg/d nicotine patch for 5 weeks prior to their quit date. They will also participate in weekly behavioral activation (BA) treatment sessions. Smokers in the VLNC Only group (n = 19) will undergo the same pharmacological pretreatment but will undergo standard counseling and health education instead of BA. Following the quit date, both groups will receive standard nicotine replacement therapy. At baseline and pre-quit, BOLD response to smoking and non-smoking rewards will be measured using fMRI after 24 hr abstinence. Latency to relapse will serve as a continuous clinical outcome measure. Participants will also receive follow-up phone calls at 6 months and 12 months post-quit to assess smoking status.
Interventions
DRUGNicotine Patch
Both groups will receive nicotine patches (21 mg/d) to wear for 1 month prior to the quit date. After the quit date, both groups will wear the nicotine patch for 8 weeks (21 mg/d for 4 weeks, 14 mg/d for 2 weeks, and 7 mg/d for 2 weeks).
DRUGSPECTRUM Nicotine Research Cigarettes (.03 mg)
For 1 month prior to their quit date, participants will switch to smoking SPECTRUM Nicotine Research Cigarettes instead of their usual brand.
BEHAVIORALBehavioral Activation
Participants in the BA+VLNC group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of behavioral activation treatment. BA components will include activity monitoring, values assessment, activity scheduling, and social contracts.
BEHAVIORALSupportive Counseling
Participants in the VLNC Only group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of supportive counseling and health education. Supportive counseling and health education will include empathic listening as well as informational content on topics of exercise, nutrition, sleep and relaxation.
Sponsors
National Institute on Drug Abuse (NIDA)
Maggie M Sweitzer, PhD
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* generally healthy * intact intellectual functioning (K-BIT2 \>79) * smoking at least 5 cigarettes per day * expired CO concentration of at least 8 ppm or urinary cotinine \> 100 ng/mL * interested in quitting smoking
Exclusion criteria
* inability to attend all experimental sessions * report of significant health problems * use of psychoactive medications or current participation in psychotherapy * current unstable psychiatric illness as assessed by clinical diagnostic interview * suicidal ideation with plan or intent * regular use of smokeless tobacco * current alcohol or drug abuse * use of illegal drugs (excluding marijuana) as measured by urine drug screen * current use of nicotine replacement therapy or other smoking cessation treatment * presence of contraindications for nicotine replacement therapy * left-handed * presence of conditions that would make MRI unsafe * claustrophobia * history of fainting * pregnant, trying to become pregnant, or breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in BOLD (Blood-oxygen-level-dependent) Response to Monetary Reward | baseline, week 5 | Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to monetary reward anticipation. BOLD signal change is estimated from the contrast of monetary reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point. |
| Change in BOLD (Blood-oxygen-level-dependent) Response to Smoking Reward | baseline, week 5 | Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to smoking reward anticipation. BOLD signal change is estimated from the contrast of smoking reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point. |
| Number of Participants Who Relapsed or Are Presumed to Have Relapsed | weeks 6 to 13 | Relapse is defined as return to 7 consecutive days of smoking. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BA (Behavioral Activation) + VLNC (Very Low Nicotine Cigarettes) Participants will receive Nicotine Patch, SPECTRUM Nicotine Research Cigarettes (.03), and behavioral treatment prior to quit attempt, followed by standard nicotine replacement therapy with Nicotine Patch during the quit attempt. Behavioral treatments in this condition will include standard smoking cessation counseling plus behavioral activation therapy aimed at increasing reinforcement from non-drug rewards.
Nicotine Patch: Both groups will receive nicotine patches (21 mg/d) to wear for 1 month prior to the quit date. After the quit date, both groups will wear the nicotine patch for 8 weeks (21 mg/d for 4 weeks, 14 mg/d for 2 weeks, and 7 mg/d for 2 weeks).
SPECTRUM Nicotine Research Cigarettes (.03 mg): For 1 month prior to their quit date, participants will switch to smoking SPECTRUM Nicotine Research Cigarettes instead of their usual brand.
Behavioral Activation: Participants in the BA+VLNC group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of behavioral activation treatment. BA components will include activity monitoring, values assessment, activity scheduling, and social contracts. | 16 |
| VLNC (Very Low Nicotine Cigarettes) Only Participants will receive Nicotine Patch, SPECTRUM Nicotine Research Cigarettes (.03), and behavioral treatment prior to quit attempt, followed by standard nicotine replacement therapy with Nicotine Patch during quit attempt. Behavioral treatments in this condition will include standard smoking cessation counseling plus supportive counseling and health education.
Nicotine Patch: Both groups will receive nicotine patches (21 mg/d) to wear for 1 month prior to the quit date. After the quit date, both groups will wear the nicotine patch for 8 weeks (21 mg/d for 4 weeks, 14 mg/d for 2 weeks, and 7 mg/d for 2 weeks).
SPECTRUM Nicotine Research Cigarettes (.03 mg): For 1 month prior to their quit date, participants will switch to smoking SPECTRUM Nicotine Research Cigarettes instead of their usual brand.
Supportive Counseling: Participants in the VLNC Only group will undergo 8 60-minute behavioral sessions (4 pre-quit, 1 on quit day, and 3 post-quit) including 15 min of standard smoking cessation counseling and 45 minutes of supportive counseling and health education. Supportive counseling and health education will include empathic listening as well as informational content on topics of exercise, nutrition, sleep and relaxation. | 19 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | PI withdrawn due to missed visits | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | BA (Behavioral Activation) + VLNC (Very Low Nicotine Cigarettes) | Total | VLNC (Very Low Nicotine Cigarettes) Only |
|---|---|---|---|
| Age, Continuous | 38.2 years STANDARD_DEVIATION 10.3 | 37.9 years STANDARD_DEVIATION 9.2 | 37.6 years STANDARD_DEVIATION 8.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 4 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants | 30 Participants | 16 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 8 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 4 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 22 Participants | 13 Participants |
| Region of Enrollment United States | 16 Participants | 35 Participants | 19 Participants |
| Sex: Female, Male Female | 9 Participants | 21 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 14 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 19 |
| other Total, other adverse events | 13 / 16 | 16 / 19 |
| serious Total, serious adverse events | 0 / 16 | 0 / 19 |
Outcome results
Primary
Change in BOLD (Blood-oxygen-level-dependent) Response to Monetary Reward
Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to monetary reward anticipation. BOLD signal change is estimated from the contrast of monetary reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point.
Time frame: baseline, week 5
Population: Participants without good fMRI data at baseline or week 5 (due to missed session, signal dropout, or artifacts) are not included in analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BA (Behavioral Activation) + VLNC (Very Low Nicotine Cigarettes) | Change in BOLD (Blood-oxygen-level-dependent) Response to Monetary Reward | -0.085 fMRI BOLD signal | Standard Deviation 0.21 |
| VLNC (Very Low Nicotine Cigarettes) Only | Change in BOLD (Blood-oxygen-level-dependent) Response to Monetary Reward | -0.067 fMRI BOLD signal | Standard Deviation 0.36 |
p-value: 0.891t-test, 2 sided
Primary
Change in BOLD (Blood-oxygen-level-dependent) Response to Smoking Reward
Effects of BA+VLNC (vs. VLNC Only) on pre-quit changes in fMRI BOLD response to smoking reward anticipation. BOLD signal change is estimated from the contrast of smoking reward anticipation vs neutral anticipation, and extracted from voxels within the ventral striatum at each time point.
Time frame: baseline, week 5
Population: Participants without good fMRI data at baseline or week 5 (due to missed session, signal dropout, or artifacts) are not included in analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BA (Behavioral Activation) + VLNC (Very Low Nicotine Cigarettes) | Change in BOLD (Blood-oxygen-level-dependent) Response to Smoking Reward | 0.011 fMRI BOLD signal | Standard Deviation 0.157 |
| VLNC (Very Low Nicotine Cigarettes) Only | Change in BOLD (Blood-oxygen-level-dependent) Response to Smoking Reward | -0.036 fMRI BOLD signal | Standard Deviation 0.226 |
p-value: 0.571t-test, 2 sided
Primary
Number of Participants Who Relapsed or Are Presumed to Have Relapsed
Relapse is defined as return to 7 consecutive days of smoking.
Time frame: weeks 6 to 13
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BA (Behavioral Activation) + VLNC (Very Low Nicotine Cigarettes) | Number of Participants Who Relapsed or Are Presumed to Have Relapsed | 9 Participants |
| VLNC (Very Low Nicotine Cigarettes) Only | Number of Participants Who Relapsed or Are Presumed to Have Relapsed | 9 Participants |
p-value: 0.739Regression, Cox