Nicotine Dependence, Nicotine Withdrawal
Conditions
Keywords
Tobacco, Nicotine, Smoking, Varenicline, Bupropion, Human laboratory study, Stress tolerance, Startle response, Cognitive assessment, Progressive ratio, Motivation
Brief summary
The objective of this proposal is to elucidate effects of bupropion SR + varenicline on smoking-cessation related processes in early abstinence using a human laboratory model. A within-subjects design will be used to assess the additive effects of bupropion and varenicline in 48 treatment seeking smokers \[bupropion SR (300 mg/day)+placebo, varenicline (2 mg/day+placebo, and bupropion SR (300 mg/day)+varenicline (2 mg/day)\]. Outcomes include withdrawal and craving, cognition, stress tolerance, anxiety, the reinforcing effects of smoking, and smoking topography. Hypotheses: We hypothesize that greatest treatment effects will be observed in the bupropion SR+varenicline group followed by varenicline+placebo and bupropion SR+placebo groups.
Interventions
DRUGBupropion
Form: tablet, Dosage, Frequency, Duration: Days 1-3, 150 mg, q.d., Days 4-11, 150 mg, b.i.d.
DRUGVarenicline
Form: tablet, Dosage, Frequency, Duration: Days 1-3, .5 mg, q.d., Days 4-7, .5 mg, b.i.d., Days 8-11, 1 mg, b.i.d.
Sponsors
National Institute on Drug Abuse (NIDA)
Pfizer
University of Minnesota
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. 18 years and up. 2. Smoked at least 10 cigarettes/day for at least 1 year. 3. English speaking and reading. 4. Females who are of childbearing potential must practice effective contraception and meet the following criteria: 1. Are instructed to avoid pregnancy through 30 days after the last dose of study medication. 2. Have a negative urine pregnancy test at baseline. 3. Agree to use of the birth control methods listed: an oral contraceptive agent, an intrauterine device (IUD), an implantable contraceptive (e.g., Norplant), or an injectable contraceptive (e.g., Depo-Provera) for at least one month prior to entering the study and will continue its use through at least 30 days after the last dose of the study medication. A barrier method of contraception (e.g., condom or diaphragm with spermicide) while participating in the study and 30 days after the last dose of study medication. 5. Willingness to not use illicit drugs during study period including marijuana.
Exclusion criteria
1. Any unstable medical condition. 2. Unstable angina, myocardial infarction, or coronary angioplasty within the past 3 months or an untreated cardiac dysrhythmia. 3. Personal history of seizures. 4. Closed head trauma with any loss of consciousness or amnesia in the last 5 years. 5. A history of closed head trauma with \> 30 minutes of loss of consciousness or amnesia or resulting in skull fracture or subdural hematoma/brain contusion. 6. A history of psychosis, bipolar disorder, bulimia or anorexia nervosa. 7. Current depression as assessed by Center for Epidemiologic Studies Depression Scale (CES-D). 8. Medications that might affect the outcome measures of nicotine reward, cognition, anxiety, and stress will also be a basis for exclusion. These medications include psychotropic drugs (i.e., anti-psychotic, anti-depressant, anti-anxiety, or stimulant), anti- hypertensive agents (e.g., beta-blockers), and other drugs that can influence the outcome domains. 9. Active substance abuse other than nicotine. 10. Used an investigational drug within the last 30 days. 11. Are currently using a behavioral or pharmacologic tobacco treatment. 12. Use of bupropion or varenicline in the previous 30 days. 13. Current (past 14 days) use of antipsychotic or antidepressant medications. 14. An allergy to bupropion or varenicline. 15. Untreated hypertension or baseline systolic blood pressure \> 180 or diastolic \> 100. 16. Impaired kidney function (creatinine clearance \< 30). 17. Having plans to leave the immediate geographical area within 2 months. 18. Unwillingness or inability to give written informed consent. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Withdrawal and Craving | Change from Base line to 33 weeks | Subjects were analyzed by how they self reported withdrawal or craved cigarettes during treatment Subjects self reported during study visits along with surveys |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Bupropion + Placebo Varenicline Order 1: Bupropion + Placebo Varenicline \\Varenicline + Placebo Bupropion; Order 2: Varenicline + Placebo Bupropion \\Bupropion + Placebo Varenicline
Bupropion SR: Form: tablet, Dosage, Frequency, Duration: Days 1-3, 150 mg, q.d., Days 4-11, 150 mg, b.i.d.
Varenicline: Form: tablet, Dosage, Frequency, Duration: Days 1-3, .5 mg, q.d., Days 4-7, .5 mg, b.i.d., Days 8-11, 1 mg, b.i.d. | 60 |
| Upropion + Varenicline Order 1: Bupropion + Varenicline \\Varenicline + Placebo Bupropion; Order 2: Varenicline + Placebo Bupropion \\Bupropion + Varenicline
Bupropion SR: Form: tablet, Dosage, Frequency, Duration: Days 1-3, 150 mg, q.d., Days 4-11, 150 mg, b.i.d.
Varenicline: Form: tablet, Dosage, Frequency, Duration: Days 1-3, .5 mg, q.d., Days 4-7, .5 mg, b.i.d., Days 8-11, 1 mg, b.i.d. | 61 |
| Total | 121 |
Baseline characteristics
| Characteristic | Upropion + Varenicline | Total | Bupropion + Placebo Varenicline |
|---|---|---|---|
| Age, Continuous | 40.2 years STANDARD_DEVIATION 11.3 | 39.85 years STANDARD_DEVIATION 11.25 | 39.5 years STANDARD_DEVIATION 11.2 |
| Race/Ethnicity, Customized White | 52 Count of particpants | 108 Count of particpants | 56 Count of particpants |
| Region of Enrollment United States | 61 participants | 121 participants | 60 participants |
| Sex: Female, Male Female | 30 Participants | 60 Participants | 30 Participants |
| Sex: Female, Male Male | 31 Participants | 61 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 60 | 0 / 61 |
| serious Total, serious adverse events | 0 / 60 | 0 / 61 |
Outcome results
Primary
Nicotine Withdrawal and Craving
Subjects were analyzed by how they self reported withdrawal or craved cigarettes during treatment Subjects self reported during study visits along with surveys
Time frame: Change from Base line to 33 weeks
Population: All efforts were made to contact the PI/study team members, but were unsuccessful. No outcome measure study data are available.
p-value: 0.07SAS