Comparison of Varenicline and Placebo for Smoking Cessation in Schizophrenia

Study Overview
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Brief Summary
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The purpose of this proposed pilot study is to examine the use of varenicline in people with schizophrenia to specifically assess tolerability and efficacy for smoking cessation. Specifically, The primary objective of this pilot study is to determine if taking of varenicline along with an individual smoking cessation supportive program is a safe and effective treatment of nicotine addiction in schizophrenic patients. We hypothesize that the varenicline treated patients will achieve higher rates of smoking cessation than those who receive placebo and individual support.

Detailed Description
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The primary objective of the data analysis will be to measure the rate of smoking cessation in the two treatment groups. Smoking cessation will be measured weekly through a composite measure of self-reported abstinence, end expired carbon monoxide (CO) of less than C10 ppm and urine cotinine dipstick measure of < 30 ng/ml. The primary endpoint will be point prevalence at 12 weeks. The four week continuous abstinence rate for the last four weeks of the treatment phase will also be evaluated. The point prevalence abstinence rates will also be obtained. The secondary objective is to determine whether smoking cessation is associated with a worsening of cognition and psychiatric symptomology. We hypothesize that subjects who achieve abstinence in the varenicline group will not show worsening on neurocognitive and symptom measures compared to abstinence subjects in the placebo group. Lastly, we will attempt to identify any clinical or topographic markers which predict cessation.

Official Title
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Comparison of Varenicline and Placebo for Smoking Cessation in Schizophrenia

Conditions
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Cigarette Smoking, Schizophrenia

Intervention / Treatment
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* Drug: varenicline
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-64 Regular ten cigarette per day smoker for one year Nicotine Dependency Score greater than or equal to four DSM-IV Diagnosis of Schizophrenia or Schizoaffective disorder Psychiatric medication regimen unchanged for at least 90 days Psychiatric medication dosage unchanged for at least 30 days Exclusion Criteria: Psychiatric hospitalization in last 6 months Meets criteria for current Major Depressive Disorder or has a score of greater than 10 on the Calgary Depression Scale (see withdrawal criteria) Suicide or homicide ideation with a plan in the last six months Life time history of suicide attempt Has had a diagnosis of Schizophrenia or Schizoaffective disorder for less than three years Current treatment with Bupropion SR DSM-IV diagnosis of alcohol or substance dependence within last 6 months* DSM-IV diagnosis of alcohol or substance abuse within three months * Pregnancy or lactation in females (+HCG) Use of tobacco product other than cigarettes Use of nicotine replacements Unstable or serious medical condition in last 6 months Regular use of cimetidine (OTC or Rx) *Substance abuse/dependency exclusions do not apply to abuse of or dependence on nicotine.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: varenicline<br> | Drug: varenicline<br>* Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.<br>* Other names: chantix, study drug;|
| Placebo Comparator: placebo<br> | Drug: placebo<br>* At the end of Pre-med week 1, subjects will receive study medication with the target quit date being the following week. Subjects will be randomized to receive either active drug or matching placebo capsules using the following titration schedule: 0.5mg for three days, 0.5mg twice daily for the next four days, then 1mg twice daily for the rest of the treatment phase. Subjects will be evaluated weekly for abstinence through self report, end expired CO and urine dipstick for cotinine.<br>* Other names: sugar pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of ExpiredCO Level From Baseline | End expired carbon monoxide (CO) level change from baseline to determine participants' level of smoking reduction by treatment assignment. Larger negative values represent a greater level of smoking reduction. | Weekly for 12 weeks | 
| Level of Nicotine Dependence by Treatment Assignment | Nicotine dependence was measured using the total score from the Fagerstrom Test for Nicotine Dependence (FTND) assessment. The total score is computed by adding the scores from the five subscales. Total scores range from 1-10, with lower scores representing a smaller degree of nicotine dependence. | Weekly for 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Psychiatric Rating Scale (BPRS) - Total Score | The total BPRS score is calculated by adding the scores for subscales #1-#18. Each scale ranges from 1=Not Present to 7=Very Severe. Total scores range from a minimum score of 18 to a maximum score of 126. A higher total score indicates a more severe psychiatric symptom rating. | Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12. | 
| Brief Psychiatric Rating Scale (BPRS) - Psychosis Score | The psychosis score is calculated by adding the scores for scales #4 Conceptual Disorganization, #11 Suspiciousness, #12 Hallucinatory Behavior, and #15 Unusual Thought Content. Each scale ranges from 1=Not Present to 7=Very Severe. The minimum psychosis score is 4 and the maximum psychosis score is 28. A higher score indicates a more severe psychosis rating. | Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12. | 
| Brief Psychiatric Rating Scale (BPRS) - Anxiety/Depression Score | The anxiety/depression score is calculated by adding the scores for scales #2 Anxiety and #9 Depressive Mood. Each scale ranges from 1=Not Present to 7=Very Severe. The minimum anxiety/depression score is 2 and the maximum psychosis score is 14. A higher score indicates a more severe anxiety/depression rating. | Baseline (week 0) then again during the Treatment Phase at weeks 1, 2, 4, 8, and 12. | 
| Side Effects | Side effects (33 items) were measured using a Side Effects Checklist (SEC). The percentage of participants endorsing each side effect were reported regardless of the severity or relation to study drug. | Weekly for 12 weeks |