Clinical trial NCT00621777
Conditions: Schizophrenia Schizoaffective Disorder Bipolar Disorder Smoking
Keywords: schizophrenia bipolar disorder varenicline smoking cessation relapse prevention cognitive behavioral therapy
Sponsor: Massachusetts General Hospital
Start date: 2008-02-01; Completion date: 2013-05-01
Enrollment: 247 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Varenicline (Chantix) is a smoking cessation treatment that was approved in 2006 by the FDA for treatment of nicotine dependence and may be particularly beneficial in smokers with schizophrenia or bipolar disorder. Early experience with varenicline indicates that it will be effective for smoking cessation in schizophrenia and in addition, has the potential to be therapeutic for cognitive dysfunction in this population. In addition, more data is needed to evaluate the safety, tolerability and effectiveness of Varenicline in people with bipolar disorder.

To assess this possibility, we will evaluate the safety and efficacy of 12 months of varenicline in schizophrenia or bipolar disorder patients who are able to quit smoking in the short term with this treatment. To do so, we will enroll 324 smokers with schizophrenia or bipolar disorder from 6 mental health clinics in Massachusetts, New Hampshire, Michigan and Minnesota into an open, 12-week smoking cessation program that includes varenicline added to weekly group cognitive behavioral therapy (CBT). Those who achieve at least 2 weeks of continuous abstinence during the last 2 weeks of the open intervention will be randomized to the relapse prevention phase: a 40-week, double blind, placebo-controlled trial of varenicline at the dose used to quit smoking added to a tapering CBT schedule. Participants will then discontinue study medications and behavioral treatment and enter a 3-month follow up phase.

Detailed description:
Participants will be moderate to heavy smokers, aged 18-70, who have smoked an average of ≥10 cigarettes/day for the past year and who have not quit during the past year for a period \>1 month.

During a 12-week open phase smoking cessation program, eligible subjects will be given active varenicline in addition to a 13-session weekly cognitive behavioral therapy program for smoking cessation. Dr. Evins (Principal Investigator) or a co-investigator will meet with subjects individually at Baseline of the Smoking Cessation Program to assess their medical eligibility for varenicline. A chart review will also be conducted by a research physician or psychiatrist.

Dr. Evins or another prescribing co-investigator will write a prescription for varenicline for each medically eligible subject. Subjects will receive their study medication at the end of each weekly group meeting. Any subject who experiences a serious side effect to the medication will meet with Dr. Evins or another medical co-investigator individually.

Subjects will set quit dates between the fourth and fifth CBT session weeks. Self-reports and exhaled carbon monoxide (CO) levels will be used to assess smoking status. Those subjects who have been abstinent for ≥2 weeks at the end of the 12th session group will be eligible for a 40-week relapse prevention program. After enrolling in the Relapse Prevention Program, subjects will be randomized to receive varenicline or placebos in addition to CBT for relapse prevention.

At Week 12 (the week before the end of the Smoking Cessation Program), Dr. Evins or another prescribing co-investigator will write prescriptions for subjects eligible for the randomized Relapse Prevention phase (i.e. successful quitters); these prescriptions will be sent to the Massachusetts General Hospital Research Pharmacy, where they will be filled according to the randomization code that the a research pharmacist will create.

When subjects come for the CBT orientation group session of the Relapse Prevention Program (Week 13), they will receive a 1-month supply of varenicline or placebo pill. During this randomized Relapse Prevention phase, medication compliance will be assessed at every group meeting by pill-count. Subjects will be asked about medication compliance and side effects at each group by the CBT group leaders and staff.

Any subject who experiences a serious side effect to the medication will meet with Dr. Evins or another medical co-investigator individually. In addition, Dr. Evins or a medical co-investigator will review the adverse events forms for each subject every week. Again, self-report and CO levels will be used to monitor smoking status.

Before and during both the open and randomized relapse prevention phases, subjects will be periodically assessed for cognitive performance, clinical characteristics, and adverse events in order to evaluate effects of withdrawal, predictors of cessation and relapse, and medication side effects. Following the completion of the 40-week relapse prevention phase, 3 follow-up assessments will be performed over a 3-month period to evaluate smoking status, cognitive functioning, and clinical effects.

Arms: arm 1: Varenicline is a partial agonist at alpha4beta2 nicotinic acetylcholine receptors (nAChRs) and a full agonist at alpha 7 nAChRs that has been shown to be effective for smoking cessation compared with placebo and bupropion, with effects on abstinence rates for up to one year. Varenicline has demonstrated safety when dosed at 1 mg twice per day for up to one year. Because varenicline, at a dose of 1 mg twice per day, may be a more effective treatment for sustained abstinence than bupropion, it was chosen as the medication intervention for this study. arm 2: None
Interventions: intervention 1: Varenicline intervention 2: Placebo
Intervention descriptions: intervention 1: At each weekly study visit from the baseline visit to study week 11, ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks.

In addition, participants who enter the relapse prevention phase and are randomized to the varenicline condition will receive varenicline at the dose used to attain initial abstinence for 40 weeks. intervention 2: At each weekly study visit from the baseline visit to study week 11,ALL subjects will receive a one-week supply of varenicline with instructions on how to take the study medication. Titration is as follows: 0.5 mg varenicline per day for 3 days, then 0.5 mg twice per day for 4 days, and then 1 mg twice per day for 11 weeks.

In addition, participants who enter the relapse prevention phase and are randomized to the placebo condition will receive placebo pills for 40 weeks.

Protocol documents: