STOP Study: Effectiveness of Zyban in a Clinical Population

• ClinicalTrials.gov Identifier: NCT01015170
• Recruitment Status: Completed
• First Posted: November 18, 2009
• Results First Posted: March 27, 2017
• Last Update Posted: March 27, 2017
• Sponsor: Centre for Addiction and Mental Health
• Collaborator: Ontario Ministry of Health and Long Term Care
• Information provided by (Responsible Party): Dr. Peter Selby, Centre for Addiction and Mental Health

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cigarette Smoking; Nicotine Addiction; Smoking Cessation	Drug: bupropion HCl	Phase 4

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 454 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The STOP Study: Real World Effectiveness of Zyban Treatment in a Clinical Population
• Study Start Date: October 2009
• Actual Primary Completion Date: October 2015
• Actual Study Completion Date: October 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bupropion HCl; Up to 8 week of bupropion SR (150mg BID) + counseling.	Drug: bupropion HCl; 150mg BID for up to 8 weeks + counseling; Other Name: Zyban

Outcome Measures

Primary Outcome Measures :

1. 7-day Point Prevalence of Smoking Abstinence [ Time Frame: End of Treatment (8 weeks after Zyban start date) ]
   Number of participants who report "Not Smoking (not even a puff) in past 7 days" when asked at week 8

Secondary Outcome Measures :

1. Serious Quit Attempt (at Least 24 Hours of Abstinence) [ Time Frame: End of Treatment (8 weeks after Zyban start date) ]
   Number of participants who report a serious quit attempt at End of treatment
2. 7-day Point Prevalence of Smoking Abstinence [ Time Frame: 6 months after Zyban start date ]
   Number of participants who report "Not Smoking (not even a puff) in past 7 days" when asked 6 months after Zyban start date

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, Ontario

The Youth Centre

Ajax, Ontario, Canada

Cottage Country Family Health Team

Bracebridge, Ontario, Canada

Bramalea Community Health Centre

Brampton, Ontario, Canada

Aberdeen Downtown Nurse Practitioner Clinic

Brantford, Ontario, Canada

Beausoleil Family Health Centre

Christian Island, Ontario, Canada, L9M0A9

Georgian Bay Family Health Team

Collingwood, Ontario, Canada

North Renfrew Family Health Team

Deep River, Ontario, Canada

Elliot Lake Family Health Team

Elliot Lake, Ontario, Canada

Englehart & District Family Health Team

Englehart, Ontario, Canada

Stonegate Community Health Centre

Etobicoke, Ontario, Canada

Haliburton Highlands Family Health Team

Haliburton, Ontario, Canada

Algonquin Family Health Team

Huntsville, Ontario, Canada

Mary Beglund Community Health Centre

Ignace, Ontario, Canada

NorWest Community Health Centre

Longlac, Ontario, Canada

Summerville Family Health Team

Mississauga, Ontario, Canada

Mount Forest Family Health Team

Mount Forest, Ontario, Canada

Dufferin Area Family Health Team

Orangeville, Ontario, Canada

Somerset West Community Health Centre

Ottawa, Ontario, Canada

PrimaCare Community Family Health Team

Paris, Ontario, Canada

West Durham Family Health Team

Pickering, Ontario, Canada

Prince Edward Family Health Team

Picton, Ontario, Canada

Stratford Family Health Team

Stratford, Ontario, Canada

NorWest Community Health Centre

Thunder Bay, Ontario, Canada

Sandwich Community Health Centre

Windsor, Ontario, Canada

Sponsors and Collaborators

Centre for Addiction and Mental Health

Ontario Ministry of Health and Long Term Care

Investigators

• Principal Investigator: Peter Selby, MD, MHSc; Centre for Addiction and Mental Health

More Information

Additional Information:

Click here for more information about the study: STOP Study: Effectiveness of Zyban in a Clinical Population 

Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre. 

Publications:

Alberg AJ, Stashefsky Margalit R, Burke A, Rasch KA, Stewart N, Kline JA, Ernst PA, Avey A, Hoffman SC. The influence of offering free transdermal nicotine patches on quit rates in a local health department's smoking cessation program. Addict Behav. 2004 Dec;29(9):1763-78. doi: 10.1016/j.addbeh.2004.04.007.

Ahluwalia JS, Harris KJ, Catley D, Okuyemi KS, Mayo MS. Sustained-release bupropion for smoking cessation in African Americans: a randomized controlled trial. JAMA. 2002 Jul 24-31;288(4):468-74. doi: 10.1001/jama.288.4.468.

Brody AL, Mandelkern MA, London ED, Childress AR, Lee GS, Bota RG, Ho ML, Saxena S, Baxter LR Jr, Madsen D, Jarvik ME. Brain metabolic changes during cigarette craving. Arch Gen Psychiatry. 2002 Dec;59(12):1162-72. doi: 10.1001/archpsyc.59.12.1162.

Brody AL, Mandelkern MA, Lee G, Smith E, Sadeghi M, Saxena S, Jarvik ME, London ED. Attenuation of cue-induced cigarette craving and anterior cingulate cortex activation in bupropion-treated smokers: a preliminary study. Psychiatry Res. 2004 Apr 30;130(3):269-81. doi: 10.1016/j.pscychresns.2003.12.006. Erratum In: Psychiatry Res. 2004 Dec 15;132(2):183-4.

Cokkinides VE, Ward E, Jemal A, Thun MJ. Under-use of smoking-cessation treatments: results from the National Health Interview Survey, 2000. Am J Prev Med. 2005 Jan;28(1):119-22. doi: 10.1016/j.amepre.2004.09.007.

Durcan MJ, Deener G, White J, Johnston JA, Gonzales D, Niaura R, Rigotti N, Sachs DP. The effect of bupropion sustained-release on cigarette craving after smoking cessation. Clin Ther. 2002 Apr;24(4):540-51. doi: 10.1016/s0149-2918(02)85130-x.

Hughes JR, Stead LF, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2000;(4):CD000031. doi: 10.1002/14651858.CD000031.

Hurt RD, Sachs DP, Glover ED, Offord KP, Johnston JA, Dale LC, Khayrallah MA, Schroeder DR, Glover PN, Sullivan CR, Croghan IT, Sullivan PM. A comparison of sustained-release bupropion and placebo for smoking cessation. N Engl J Med. 1997 Oct 23;337(17):1195-202. doi: 10.1056/NEJM199710233371703.

Jorenby DE, Leischow SJ, Nides MA, Rennard SI, Johnston JA, Hughes AR, Smith SS, Muramoto ML, Daughton DM, Doan K, Fiore MC, Baker TB. A controlled trial of sustained-release bupropion, a nicotine patch, or both for smoking cessation. N Engl J Med. 1999 Mar 4;340(9):685-91. doi: 10.1056/NEJM199903043400903.

Leshner AI. Addiction is a brain disease, and it matters. Science. 1997 Oct 3;278(5335):45-7. doi: 10.1126/science.278.5335.45.

Lerman C, Roth D, Kaufmann V, Audrain J, Hawk L, Liu A, Niaura R, Epstein L. Mediating mechanisms for the impact of bupropion in smoking cessation treatment. Drug Alcohol Depend. 2002 Jul 1;67(2):219-23. doi: 10.1016/s0376-8716(02)00067-4.

Shiffman S, Johnston JA, Khayrallah M, Elash CA, Gwaltney CJ, Paty JA, Gnys M, Evoniuk G, DeVeaugh-Geiss J. The effect of bupropion on nicotine craving and withdrawal. Psychopharmacology (Berl). 2000 Jan;148(1):33-40. doi: 10.1007/s002130050022.

• Responsible Party: Dr. Peter Selby, Clinician Scientist, Addictions Program, Centre for Addiction and Mental Health
• ClinicalTrials.gov Identifier: NCT01015170
• Other Study ID Numbers: 005/2008
• First Posted: November 18, 2009
• Results First Posted: March 27, 2017
• Last Update Posted: March 27, 2017
• Last Verified: February 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: No plan to share data

Keywords provided by Dr. Peter Selby, Centre for Addiction and Mental Health:

smoking cessation; nicotine addiction; Zyban; bupropion hydrochloride

Additional relevant MeSH terms:

Tobacco Use Disorder; Behavior, Addictive; Compulsive Behavior; Impulsive Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Bupropion; Antidepressive Agents, Second-Generation; Antidepressive Agents; Psychotropic Drugs; Dopamine Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Molecular Mechanisms of Pharmacological Action; Dopamine Agents; Neurotransmitter Agents; Physiological Effects of Drugs; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors