Clinical trial NCT01048944: Nicotine Replacement Therapy (NRT) and Bupropion Mechanisms of Effectiveness in Smokers
Official title: NRT & Bupropion Mechanisms of Effectiveness in Smokers: Phase IV Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Nicotine Dependence
Keywords: Electroencephalography
nicotine
bupropion
attention
drug withdrawal symptoms
Lead sponsor: Southern Illinois University Carbondale
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2010-01-14
Enrollment: 197
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: 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 sustained release (SR), 2) nicotine patch, or 3) placebo patches plus pills 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.

Detailed description: 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) placebo patch plus placebo pill. 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 patch + placebo pill; 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.)

Eligibility criteria: Inclusion Criteria:Inclusion Criteria:

* Diagnostic and Statistical Manual of the American Psychiatric Association (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

Primary outcomes:
measure: Changes in Log Brain-wave (EEG) Activity (Power [Microvolts Squared]) From Pre-quit Baseline to 66 Days Post-quit, Assessed at 3, 24, 45, and 66 Days Post-quit.
timeFrame: Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit
measure: Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence
timeFrame: Changes in log withdrawal symptoms from baseline through 66 days of abstinence
Secondary outcomes:
Other outcomes:
Locations:
city: Carbondale
country: United States
facility: Southern Illinois University
state: Illinois
Study officials:
affiliation: Southern Illinois University Carbondale
name: David G Gilbert, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gilbert DG, Rabinovich NE, Gilbert-Matuskowitz EA, Klein KP, Pergadia ML. Smoking abstinence symptoms across 67 days compared with randomized controls-Moderation by nicotine replacement therapy, bupropion, and negative-affect traits. Exp Clin Psychopharmacol. 2019 Dec;27(6):536-551. doi: 10.1037/pha0000278. Epub 2019 Mar 28.