A Comparison of Bupropion SR and Placebo for Smoking Cessation
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|ClinicalTrials.gov Identifier: NCT00176449|
Recruitment Status : Completed
First Posted : September 15, 2005
Last Update Posted : August 16, 2019
|First Submitted Date ICMJE||September 13, 2005|
|First Posted Date ICMJE||September 15, 2005|
|Last Update Posted Date||August 16, 2019|
|Study Start Date ICMJE||April 2001|
|Actual Primary Completion Date||December 2005 (Final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE
|Current Other Pre-specified Outcome Measures||Not Provided|
|Original Other Pre-specified Outcome Measures||Not Provided|
|Brief Title ICMJE||A Comparison of Bupropion SR and Placebo for Smoking Cessation|
|Official Title ICMJE||A Comparison of Bupropion SR and Placebo for Smoking Cessation|
|Brief Summary||The purpose of this study is to examine whether the adjunctive use of bupropion SR in the context of a psychoeducational program modified for people with schizophrenia might improve the likelihood of successful abstinence in this population. If bupropion SR is effective for reducing cigarette smoking, then it will be important to determine if decreased nicotine intake is associated with a worsening of psychotic, anxiety or depressive symptoms. In addition, it would be important to determine the effect that a reduction in nicotine stimulation would have on patient's cognitive functioning, as nicotinic receptors have been shown to regulate attention and memory function, and it is hypothesized that these functions are normalized by acute nicotine administration in people with schizophrenia|
After obtaining consent, patients will enter a two week stabilization phase followed by a 14 week treatment phase. The treatment phase begins with a 9 session group therapy led by clinic nurses trained in the educational model of the American Cancer Association. Subjects will begin the double-blind, randomized, placebo controlled medication phase of treatment following the third group session, which is two weeks prior to the established quit day. Patients will receive either bupropion SR 150mg twice a day (starting with 150mg once a day for three days) or placebo in addition to their usual medication regimen. Patients will be offered the use of nicotine replacement in the form of Nicorette gum from quit day through week 8, the end of the group therapy course. Correct use of the gum will be reviewed in group. Following completion of the group therapy course, patients will continue in their assigned medication group until study completion.
Prior to starting the study, subjects will receive a physical exam and ECG, if they have not had one in the last calendar year. All women will have a pregnancy test, and pregnant women will be excluded from the study. If not already completed, the following Index Assessments will be completed: Demographic forms 1 and 2, SCID, Schedule for the Deficit Syndrome, Patient Psychiatric and Medical History Form. The Fagerstrom Test for Nicotine Dependence, symptom/ functional ratings (BPRS, SANS), Extrapyramidal Rating Scale, body weight, and urinary cotinine levels will be obtained during stabilization and at treatment weeks 2, 4, 8, and 14. The MPRC Side-effect Check List will be obtained week 2 (the start of study medication) and biweekly thereafter throughout the end of the treatment phase. Expired carbon monoxide levels will be measured weekly during the study.
Patients will receive a 60 minute neuropsychological test battery during stabilization and at the end of the study. The test battery will consist of the Rey Auditory Verbal Learning Test, Brief Visuospatial Memory Test, Symbol Digit, Letter Number Sequencing, and Distractibility CPT. Similarly, at stabilization, treatment week 8, and study completion (treatment week 14), subjects will meet with a MIRECC rater to complete a Smoking History (on stabilization only), the Change Assessment Scale, Temptation to Smoke Scale, Decisional Balance Scale, and Smoking Abstinence Self-Efficacy Scale. At these time points they will also have antipsychotic blood levels drawn. Patients will be seen for follow-up assessments at 6 months and one-year. Urine cotinine levels, expired CO levels, and Fagerstrom Test for Nicotine Dependence will be obtained at this time.
A total of fifty subjects will be recruited from the Maryland Psychiatric Research Center, Outpatient Research Program (MPRC ORP), Key Point Southwest Mental Health Center, Revisions, Inc., and The Baltimore, VA. The sample will consist of 50 patients who meet the following inclusion and exclusion criteria:
Inclusion Criteria are:
Exclusion Criteria are:
Patients will be paid for their time and any inconvenience they may experience through their participation.
An educational informed consent process will be utilized, and only patients able to give informed and voluntary written consent will be able to participate in the study. Before patients are accepted into the study, they must:
MPRC booklets describing research procedures and clarifying differences between research clinical care and standard clinical care will be made available to potential subjects, referring clinicians, and interested family members. Informed consent forms are previewed by an ad hoc committee to assure MPRC and IRB feedback from the perspectives of family advocates, recipients of care, forensic psychiatry, and service system administration.
Primary outcome measures will be:
Secondary outcome measures will be:
In a preliminary study, we were able to detect a 44% reduction in expired CO with bupropion treatment. This represents a change in 1.2 SDs, a large effect size. In order to detect the same effect in the proposed double-blind study, with two-sided tests at alpha=.05 and power of 0.80, we would need 10 subjects in each treatment group. Since open labeled study designs may inflate observed effects, we have decide to include 20 subjects in each group. The primary analytic approach will use repeated measures ANCOVA, with adjustment for baseline expired CO level, with treatment assignment as the between group factor and expired CO level as the repeated measure. Since both groups will receive group therapy, the value at the end of the first week of group (before starting bupropion or placebo) will be used as the baseline for comparing patients on bupropion versus placebo. A similar approach will be used to analyze the symptom and neurocognitive measures.
The major risks of the study are the stress of and symptoms associated with nicotine withdrawal. Depressed mood, insomnia, irritability, anger, anxiety, difficulty concentrating, restlessness, decreased heart rate, and increased appetite are all common. Risks associated with the use of bupropion SR include allergic reactions (most commonly skin rashes and itching), dry mouth, insomnia, dizziness, tremor, and headaches. Of these, dry mouth and insomnia are most common. The risk of seizure, when using sustained -release bupropion in the dose range used in this study, is 0.1%, a rate similar to that of other antidepressants. Because bupropion is a weak dopamine agonist, it is possible that subjects may experience a worsening of psychosis. However, work at the MPRC ORP and other places with similar dopamine agonists showed there was no worsening in baseline psychotic symptoms, when patients remained on antipsychotics. There are studies to support the safety of combining antipsychotic medications with selective serotonin reuptake inhibitors and bupropion. However, there is always the potential for unforeseen drug interactions, with the addition of bupropion to existing medication regimens.
Use of Nicorette gum has been associated with sore throat or mouth, hiccups, tired jaws, nausea or other gastrointestinal symptoms, and rarely mouth ulcers. Nicotine intoxication from overuse of the gum is unlikely, as it is released slowly from the gastrointestinal tract and undergoes extensive presystemic metabolism.
The neuropsychological tests are associated with minimal risks. Some subjects may find the testing stressful or boring. The likelihood of this occurring is unlikely. However, frequent breaks in the testing will be allowed to insure that the subject does not become overwhelmed.
To protect privacy and confidentiality, the patient's welfare will be safeguarded by responsible, systematically controlled procedures in the collection of information for both research and clinical purposes. Recorded information for research purposes will be identified by code number rather than by name. Information gathered will be kept in a research chart maintained in a locked file cabinet. Published or presented material related to the project will not be traceable to specific individuals.
|Study Type ICMJE||Interventional|
|Study Phase ICMJE||Phase 4|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Condition ICMJE||Tobacco Use Disorder|
|Study Arms ICMJE||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Actual Enrollment ICMJE
|Original Enrollment ICMJE
|Actual Study Completion Date ICMJE||December 2005|
|Actual Primary Completion Date||December 2005 (Final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages ICMJE||18 Years to 64 Years (Adult)|
|Accepts Healthy Volunteers ICMJE||Yes|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||United States|
|Removed Location Countries|
|NCT Number ICMJE||NCT00176449|
|Other Study ID Numbers ICMJE||H-20763|
|Has Data Monitoring Committee||Yes|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement ICMJE||Not Provided|
|Responsible Party||Robert Buchanan, University of Maryland, Baltimore|
|Study Sponsor ICMJE||University of Maryland, Baltimore|
|Collaborators ICMJE||US Department of Veterans Affairs|
|PRS Account||University of Maryland, Baltimore|
|Verification Date||August 2019|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP