Nicotine Dependence, Nicotine Use Disorder
Conditions
Keywords
nicotine dependence, bupropion SR, smoking cessation, adolescents, contingency management
Brief summary
In the current proposal, we intend to study the efficacy of bupropion SR with or without combined contingency management (CM) among adolescent cigarette smokers. The proposed study will test not only medication (bupropion SR), but also combination of medication and CM in potentially improving smoking cessation outcomes AND retention of adolescent smokers in the study. Hypothesis to be tested: Bupropion SR treatment will increase abstinence from cigarette smoking (as measured by urine cotinine and continuous abstinence) in adolescent smokers as compared to treatment with placebo only. Hypothesis to be tested: Adolescent smokers treated with combined bupropion SR + contingency management (CM) treatment will have increased retention and increased abstinence rates when compared to bupropion SR alone or CM + placebo treated groups (as measured by decreased drop-out of participants, urine cotinine and continuous abstinence). Hypothesis to be tested: CM will increase the abstinence from cigarette smoking (as measured by urine cotinine and continuous abstinence) in adolescent smokers as compared to treatment with placebo only.
Detailed description
To test the hypotheses, 216 adolescent smokers will be recruited. Fifty-four adolescent smokers will be recruited in each of the four groups: bupropion SR only, bupropion SR + CM, CM + placebo, and placebo only. The cells will be balanced for gender and attention deficit hyperactivity disorder using permuted block randomization. A counseling intervention was added for all groups because it was reasoned that it would be unethical not to provide an active treatment to cigarette smoking adolescents. The counseling intervention will consist of two quit smoking brochures that provide information on tips to help quit smoking. The study will consist of a one-week lead in period followed by a six-week treatment trial. For the medication groups, medications will be titrated during the one-week lead-in period. The primary outcome measure is urine cotinine and self-report of cigarette use collected using the Time-Line Follow-Back at the end of six weeks.
Interventions
OTHERPlacebo
Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment
DRUGBupropion SR
Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment
BEHAVIORALContingency Management
Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.
Sponsors
National Institute on Drug Abuse (NIDA)
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
Yes
Inclusion criteria
1. Regular cigarette smokers smoking at least 5 cigarettes per day as derived by Time-Line Follow-Back method (Sobell et al., 1988). Average number of cigarettes per day (over past 30 days) will be used. Five cigarettes per day may seem low, but based on previous studies, adolescents tend to smoke fewer cigarettes per day as compared to adults. 2. Baseline urine cotinine level greater than 100 ng/ml. 3. Age range of 12 - 21 4. If under 18 yr. of age, parent(s) or guardian(s) able to participate in informed consent and initial assessment, or the participant must provide evidence of emancipated status. 5. For post menarchal female participants: agree to use birth control to avoid pregnancy.
Exclusion criteria
1. Active substance abuse/dependence (other than nicotine) within 2 weeks prior to participating in the study 2. Lifetime bipolar affective disorder (BPAD), psychosis, eating disorders. Bupropion may have adverse consequence on participants with these psychiatric diagnoses. 3. Current major depressive disorders. Since bupropion is also an antidepressant, this criteria is to minimize the confound of depressive disorder during the study. History of depressive disorders and current attention deficit hyperactivity disorder (ADHD) will not be an exclusion. We will use permuted block randomization procedure to balance the groups for ADHD. 4. Pregnancy or lactation. The safety of bupropion in pregnancy and during lactation is not well studied. 5. History of seizure disorder or predisposition to seizures (e.g., history of significant head trauma, currently taking medications that lower seizure threshold), since bupropion can lower seizure threshold. 6. History of severe renal, hepatic, neurological, or chronic pulmonary disease. This criterion was chosen due to the hepatic metabolism of bupropion. 7. Unstable medical problems 8. Allergy to bupropion 9. Current treatment with any other medication containing bupropion 10. Current treatment with any monoamine oxidase (MAO) inhibitors currently or within 2 weeks of starting the study since there may be serious and severe medical interactions between MAO inhibitors and bupropion SR. 11. Current treatment with nicotine replacement therapy (NRT) 12. History of intolerance or non-response to bupropion SR. 13. Current (past month) suicide ideation 14. Suicide attempt (past year)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Biologically-verified 7-day Point Prevalence Smoking Abstinence | End of treatment (week 6) | Self-reported abstinence for the past 7 days, confirmed by urine cotinine ≤100 ng/mL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupropion SR + Contingency Management Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits.
Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment
Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence. | 37 |
| Placebo + Contingency Management Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management, with escalating rewards for abstinence (and re-sets for non-abstinence) at twice-weekly visits.
Contingency Management: Contingency Management provided at twice-weekly visits during the 6-week active treatment. Escalating schedule, with resets, reinforcing smoking abstinence.
Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment | 36 |
| Bupropion SR + No Contingency Management Bupropion SR capsules, with goal dose of 300 mg/day, for 6 weeks of treatment. Contingency Management is not provided in this arm.
Bupropion SR: Bupropion SR, with goal dose 300 mg/day, for 6 weeks of active treatment | 29 |
| Placebo + No Contingency Management Placebo capsules, matched in appearance to Bupropion SR capsules, for 6 weeks of treatment. Contingency Management is not provided in this arm.
Placebo: Placebo, matched in appearance to Bupropion SR, for 6 weeks of treatment | 32 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 12 | 13 | 14 | 10 |
| Overall Study | Withdrawal by Subject | 8 | 5 | 4 | 4 |
Baseline characteristics
| Characteristic | Placebo + No Contingency Management | Total | Bupropion SR + Contingency Management | Placebo + Contingency Management | Bupropion SR + No Contingency Management |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 15 Participants | 62 Participants | 17 Participants | 16 Participants | 14 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants | 72 Participants | 20 Participants | 20 Participants | 15 Participants |
| Age, Continuous | 19 years STANDARD_DEVIATION 1.8 | 18.5 years STANDARD_DEVIATION 1.9 | 18.4 years STANDARD_DEVIATION 1.9 | 18.4 years STANDARD_DEVIATION 1.9 | 18.1 years STANDARD_DEVIATION 1.9 |
| Sex: Female, Male Female | 15 Participants | 56 Participants | 16 Participants | 14 Participants | 11 Participants |
| Sex: Female, Male Male | 17 Participants | 78 Participants | 21 Participants | 22 Participants | 18 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 | 0 / 37 | 0 / 36 | 0 / 29 | 0 / 32 |
| other Total, other adverse events | 22 / 37 | 14 / 36 | 25 / 29 | 15 / 32 |
| serious Total, serious adverse events | 0 / 37 | 0 / 36 | 0 / 29 | 0 / 32 |
Outcome results
Primary
Biologically-verified 7-day Point Prevalence Smoking Abstinence
Self-reported abstinence for the past 7 days, confirmed by urine cotinine ≤100 ng/mL
Time frame: End of treatment (week 6)
Population: Intent-to-treat analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Bupropion SR + Contingency Management | Biologically-verified 7-day Point Prevalence Smoking Abstinence | 10 participants |
| Placebo + Contingency Management | Biologically-verified 7-day Point Prevalence Smoking Abstinence | 3 participants |
| Bupropion SR + No Contingency Management | Biologically-verified 7-day Point Prevalence Smoking Abstinence | 3 participants |
| Placebo + No Contingency Management | Biologically-verified 7-day Point Prevalence Smoking Abstinence | 3 participants |
p-value: 0.0795% CI: [0.9, 14.4]Regression, Logistic