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

Nicotine Dependence Clinical Trial

Official title:

NRT & Bupropion Mechanisms of Effectiveness in Smokers: Phase IV Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048944
• Other study ID #: NIH/NIDA-2R01DA012289
• Secondary ID: 2R01DA012289
• Status: Completed
• Phase: Phase 4
• First received: January 13, 2010
• Last updated: November 18, 2014
• Start date: June 2005
• Est. completion date: January 2013

Study information

• Verified date: November 2014
• Source: Southern Illinois University Carbondale
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 197
• Est. completion date: January 2013
• Est. primary completion date: January 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Nicotine Dependence

Intervention

Drug:
• Bupropion SR
150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down.
• Nicotine Patch
Nicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days
• Placebo Patch and Placebo Pill
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. The placebo patches were given beginning 1st day cessation: 21 mg size (but actually placebo)/24 days, 14 mg size (actually placebo)/ 14 mg size (actually placebo) 14 days/, 7 mg size (actually placebo)/7 days

Locations

Country	Name	City	State
United States	Southern Illinois University	Carbondale	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Southern Illinois University Carbondale	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Brain-wave activity (EEG) was assessed using electrodes on the subject's scalp, the outputs of which were and quantified by a commercial brain wave machine. EEG was collected at frontal (e.g., Fz) and parietal (e.g., Pz) electrodes while subjects relaxed. EEG was analyzed using computer programs that measured slow-frequency EEG waves known as delta (1.5-4.5 cycles/second [cps]), theta-1 (4.5-6.0 cps), theta-2 (6.0-7.7 cps), and alpha-1 (7.8-10.0 cps), and higher frequency waves. Generally, delta, alpha-1 and theta waves reflect deactivation of the brain activity, while higher frequency waves reflect greater brain activation. Brain activity was quantified as the natural log of EEG power [microvolts squared] as determined by the fast Fourier mathematical algorithm. Days post quit were components of Time. The primary focus was on changes in the individual subject's log theta-1, theta-2, and alpha-1 power at post-quit points in time minus the log values at the pre-quite baseline.	Mean EEG power [microvolts squared] from at baseline, 3, 24, 45, and 66 days post-quit	No
Primary	Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence	Changes in log from baseline in the widely used Shiffman-Jarvik Withdrawal "craving" and "psychological symptom" scores through 66 days of abstinence. Post-quit changes were assessed at days 3, 24, 45, and 66 of abstinence. The maximal range of value raw for craving is from "5" = (no craving) to "47" (maximally strong craving), while that for psychological symptoms is from "5" (no symptoms) to "60" (maximally intense symptoms of across multiple symptoms). Because the subtraction of logs is equivalent to the ratio of the two scores, a difference in logs (base 10) with a value of "1" is equal to an increase by a factor of 10, while a value of "0" is no change, and values of less than "0" are decreases below baseline values.	Changes in log withdrawal symptoms from baseline through 66 days of abstinence	No