Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers

Official Title: “NRT & Bupropion Mechanisms of Effectiveness in Smokers: Phase IV Trial”

The purpose of this study is to better characterize differences in mood, attention, brain activation patterns underlying the beneficial effects of pharmacological treatments previously demonstrated to be help individuals successfully quit tobacco smoking. Smokers will be randomly assigned to one of three treatments: 1) bupropion SR, 2) nicotine patch, or 3) placebo pills and patches across a 45-day period with a 3-week intensive post-treatment follow-up. In addition, 20 percent of the subjects will be randomized to a delayed-quit control group.

The first aim of this revised proposal is to accurately assess the duration and trajectories of smoking abstinence symptoms and associated biobehavioral indices across 66 days of quitting smoking in 3 different treatment groups: 1) bupropion SR (BUP), 2) transdermal nicotine patch (TNP), and 3) a placebo. Study sensitivity and accuracy will be maximized by using procedures designed to maximize abstinence and minimize study dropout. The second aim is to characterize brain and psychological mechanisms by which BUP and TNP promote abstinence. While the efficacies of BUP and TNP in promoting smoking abstinence have been repeatedly demonstrated, little is known about the mechanisms mediating this efficacy. The final primary goal of this competitive continuation proposal is to characterize individual differences in psychological and brain mechanisms mediating the beneficial effects of BUP and TNP on smoking abstinence and withdrawal symptoms. A secondary goal is to assess the ability of a battery of innovative brain and biobehavioral measures of attention and affect to predict relapse.

To achieve these goals, the effects of quitting smoking with or without the help of TNP and BUP will be assessed intensively across 66 days of abstinence. Dependent measures will be mood, vigilance, attentional bias to smoking and emotional stimuli, and related physiological measures (resting EEG activation and activation asymmetry indices of affective states and traits, and event-related potential activity elicited by emotional and smoking stimuli). Smokers will be randomly assigned to one of three immediate-quit groups (N = 60 per group): (1) bupropion + placebo patch, (2) placebo pill + nicotine patch, and (3) placebo pill + placebo patch; or to a fourth (control) group (N = 40) that will quit after the final experimental session (after the other subjects have completed their 66-day* abstinence period). Subjects in the 3 treatment groups and the control group will have the same set of biobehavioral measures assessed during the experimental sessions at the same points in time. It is hypothesized that BUP and TNP will have both common and unique mechanisms by which they reduce withdrawal symptoms and that gender and personality traits will moderate the effects of these treatments. (Note.* To avoid final-session mood and arousal effects subjects will actually quit for 67 days, but biobehavioral measures will be collected on the 66th day of abstinence.)         

Intervention(s) in this Clinical Trial

• Drug: Bupropion SR
  • 150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down.
• Drug: Nicotine
  • Nicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days
• Drug: Placebo pill and Placebo Patch
  • 150 encapsulated placebo pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down. Placebo patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days.
• Other: Delayed-Quit Control
  • Delayed-quit until after 67-day period corresponding to drug treatments.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: Bupropion SR
• Active Comparator: Nicotine Patch
• Placebo Comparator: Placebo Patch and Placebo Pill
• No Intervention: Delayed-quit Smoke control

Primary Measures

• withdrawal symptom severity
  • Time Frame: 67 days
    Safety Issue?: No

Secondary Measures

• biobehavioral brain mood attention factors
  • Time Frame: 67 days
    Safety Issue?: No

Inclusion Criteria:Inclusion Criteria:

• DSM-IV diagnosis of nicotine dependence with psychological dependence
• Smokes at least 10 cigarettes per day for the three months prior to enrollment
• Currently seeking treatment for nicotine dependence
• Medically healthy on the basis of physical examination and medical history, vital signs,
• Females must use an effective method of contraception for the duration of the study

Exclusion Criteria:

• DSM-IV diagnosis of abuse or dependence on alcohol or drugs other than nicotine
• Current Axis I diagnosis or current treatment with psychotropic medications within the three months prior to enrollment
• History of schizophrenia or other psychotic disorders, bipolar disorder, or anxiety disorders
• Currently seeking treatment for nicotine disorders
• History of seizures or head trauma with loss of consciousness, brain contusion, or fracture
• History of significant recent violent behavior
• Blood pressure greater than 150/90
• History of eating disorders
• History of allergic reaction to any of the study medications
• Pregnant

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 55 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Investigator: Southern Illinois University Carbondale Other

Overall Clinical Trial Officials and Contacts

David G Gilbert, PhD Principal Investigator Southern Illinois University Carbondale  

Overall Contact: Norka E Rabinovich, BA 618-453-3527 norkar@siu.edu

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01048944

Study ID Number: NIH/NIDA-2R01DA012289

ClinicalTrials.gov Identifier: NCT01048944

Health Authority: United States: Institutional Review Board