STOP Study: Effectiveness of Zyban in a Clinical Population

Study Overview
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Brief Summary
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Despite the significant health, social and economic costs of cigarette smoking, 17% of Ontarians still currently smoke. Use of smoking cessation pharmacotherapy such as Zyban (bupropion HCl) has been shown to double quit rates but such medications are under-utilized by smokers attempting to quit. It has been suggested that the high price of pharmacotherapy may act as a barrier to accessing such treatment.The main objective of this study is to evaluate the methods and effectiveness of providing smokers who want to quit with 8 weeks of free Zyban in combination with smoking cessation counselling through family health teams and community health centres across the province. Hypothesis: Ontario smokers who receive 8-weeks of free bupropion in combination with brief counselling will have higher smoking cessation rates than the standard population cessation rates.

Detailed Description
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Nicotine dependence, like other addictive disorders, can be characterized as a chronic, relapsing disease (Leshner, 1997). Although there is significant morbidity and mortality associated with this disorder, the majority of smokers are not treated adequately to the widely accepted goal of complete long-term abstinence from smoking. This may be due to the under-utilization of accepted pharmacotherapies for the treatment of tobacco dependence. Bupropion (Zyban) Bupropion is the first line of non-nicotine-based pharmacotherapy for smoking cessation. Several large-scale clinical trials have shown bupropion to be an efficacious smoking cessation aid (Hurt et al., 1997; Jorenby et al., 1999; Ahluwalia et al., 2002). In one such study, a 44% abstinence rate was reported for seven weeks of treatment with bupropion at 300 mg/day, compared to 19% for placebo (Hurt et al, 1997). A recent meta-analysis has reported that bupropion monotherapy approximately doubles the rate of smoking cessation (OR 1.94) (Hughes et al, 2007). Despite its efficacy, bupropion's mechanism of action is unclear. Attenuation of abstinence-associated increase in craving and withdrawal symptoms has been suggested as possible mechanisms of bupropion's effect on smoking behaviour in a few randomized clinical trials (Jorneby et al., 1999; Shiffman et al., 2000; Lerman et al., 2002; Durcan et al, 2002). However, these effects are not universally demonstrated (Hurt et al., 1997; Shiffman et al., 2000). Other possible bio-behavioral mechanisms have remained largely unexplored. Using positron emission tomography (PET) it has been shown that in contrast to untreated smokers, when bupropion-treated smokers were exposed to cigarette-related cues there was less metabolic activation in their anterior cingulate cortex, a region of the brain previously shown to be activated by cigarette cues (Brody et al., 2004;Brody et al., 2002). STOP Study Background and Rationale Treatment with pharmacotherapy such as nicotine replacement therapy (NRT) or Zyban is a safe and effective smoking cessation strategy that can double the chance of quitting successfully over the long-term (Cornuz, 2007). However, research has shown that most smokers who are interested in quitting do not use pharmacotherapy to aid in their quit attempt. Misconceptions about the harmful effects of nicotine are a strong barrier to the use of pharmacotherapy. The cost of pharmacotherapy may also be a significant contributor to the under-utilization of smoking cessation aids such as NRT and Zyban. Karnath (2001) suggested that the high cost of successful pharmacotherapy treatment for smoking cessation may be a barrier for some individuals. Moreover, Cokkinides et al (2005) reported that smokers with private insurance were more likely to use smoking cessation pharmacotherapies than smokers without insurance. The addition of free NRT to a group behavioural cessation program substantiated these claims by showing an increase in quit rates from 38% to 65% (Alberg et al, 2004). These studies suggest that economic barriers may prevent smokers from using pharmacotherapy in their attempts to quit smoking. The study proposed herein will introduce free bupropion as another treatment option for smoking cessation for Ontario smokers. Community Health Centres and Aboriginal Health Access Centres are interdisciplinary health models that are able to help individuals who would otherwise be prevented from accessing health services due to social and geographic barriers. As they aim to eliminate these other barriers and consequently control for them, they are an ideal health model for determining whether eliminating the economic barriers of smoking cessation improves smoking cessation rates. Family Health Teams are more recent health models that provide integrated and interdisciplinary primary health care. Since they are able to treat large and diverse populations, they are an ideal health model for accessing Ontario smokers. Objectives 1. To evaluate the effectiveness of 8-weeks of free bupropion in combination with brief counselling through family health teams, community health centres and aboriginal health access centres in Ontario for smoking cessation.

Official Title
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The STOP Study: Real World Effectiveness of Zyban Treatment in a Clinical Population

Conditions
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Cigarette Smoking, Nicotine Addiction, Smoking Cessation

Intervention / Treatment
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* Drug: bupropion HCl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ontario resident 18 years of age or older Current daily cigarette smoker who smokes 10 or more cigarettes per day and has smoked > 100 cigarettes in their lifetime Want to quit smoking cigarettes within 30 days of assessment Willingness and capacity to give written informed consent and to comply with study protocol Exclusion Criteria: Enrollment in any of the STOP Study NRT models in the past 6 months Currently receiving Wellbutrin SR or any medication containing bupropion hydrochloride Current seizure disorder or history of seizures Current or prior diagnosis of bulimia or anorexia nervosa Current diagnosis of bipolar disorder History of head trauma Allergy or sensitivity to Zyban, Wellbutrin or bupropion Undergoing abrupt withdrawal from alcohol, benzodiazepines or other sedatives Currently taking monoamine oxidase (MAO) inhibitors, or thioridazine Pregnant or breastfeeding or at risk of becoming pregnant Central nervous system (CNS) tumor Severe hepatic impairment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bupropion HCl<br>Up to 8 week of bupropion SR (150mg BID) + counseling. | Drug: bupropion HCl<br>* 150mg BID for up to 8 weeks + counseling<br>* Other names: Zyban;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Point Prevalence of Smoking Abstinence | Number of participants who report Not Smoking (not even a puff) in past 7 days when asked at week 8 | End of Treatment (8 weeks after Zyban start date) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serious Quit Attempt (at Least 24 Hours of Abstinence) | Number of participants who report a serious quit attempt at End of treatment | End of Treatment (8 weeks after Zyban start date) | 
| 7-day Point Prevalence of Smoking Abstinence | Number of participants who report Not Smoking (not even a puff) in past 7 days when asked 6 months after Zyban start date | 6 months after Zyban start date | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking cessation, nicotine addiction, Zyban, bupropion hydrochloride