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

November 18, 2014 updated by: David Gilbert, Southern Illinois University Carbondale

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 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.)

Study Type

Interventional

Enrollment (Actual)

197

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Carbondale, Illinois, United States, 62901-6502
        • Southern Illinois University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Bupropion SR
150 mg bid bupropion SR
Drug: Bupropion SR
150 encapsulated pill,3 days 1x/day then 56/day for 2x/day, then 3 day 1x/day ramp-down.
Other Names:
  • ZybanSR
Active Comparator: Nicotine Patch
21mg, 14mg, 7mg
Drug: Nicotine Patch
Nicotine patch beginning 1st day cessation: 21 mg/24 days, 14 mg/14 days, 7 mg/7 days
Other Names:
  • NicodermCQ
Placebo Comparator: Placebo Patch and Placebo Pill
Individuals were placed on both a placebo patch that were the same size as active patches given to the Nicotine Patch group and were also given placebo pills were the same size and identically packaged as the active pills (bupropion) given to the Bupropion SR group.
Drug: 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
Other Names:
  • Placebo
No Intervention: Delayed-quit control
Smoke for 67 days while others have quit, then quit.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Mean EEG power [microvolts squared] from at baseline, 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
Changes in Log of Smoking Withdrawal Scores (Mood, and Depressive Symptoms) From Baseline Across 66 Days of Abstinence
Time Frame: Changes in log withdrawal symptoms from baseline through 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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southern Illinois University Carbondale

Collaborators

National Institute on Drug Abuse (NIDA)

Investigators

  • Principal Investigator: David G Gilbert, PhD, Southern Illinois University Carbondale

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2005

Primary Completion (Actual)

January 1, 2013

Study Completion (Actual)

January 1, 2013

Study Registration Dates

First Submitted

January 13, 2010

First Submitted That Met QC Criteria

January 13, 2010

First Posted (Estimate)

January 14, 2010

Study Record Updates

Last Update Posted (Estimate)

November 25, 2014

Last Update Submitted That Met QC Criteria

November 18, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIH/NIDA-2R01DA012289
  • 2R01DA012289 (U.S. NIH Grant/Contract)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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