Varenicline or Nicotine Patch and Nicotine Gum in Helping Smokers in a Methadone Treatment Program Stop Smoking

Study Overview
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Brief Summary
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RATIONALE: Varenicline, the nicotine patch, and nicotine gum help people stop smoking. It is not yet known whether varenicline is more effective than the nicotine patch given together with nicotine gum in helping smokers quit smoking. PURPOSE: This randomized clinical trial is studying varenicline to see how well it works compared with the nicotine patch given together with nicotine gum in helping smokers in a methadone treatment program stop smoking.

Detailed Description
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OBJECTIVES: Primary To determine whether varenicline, a nicotine receptor partial agonist, leads to a higher rate of smoking cessation than combination nicotine replacement therapy with nicotine patch prescription plus ad libitum nicotine gum delivery in methadone-maintained smokers. Secondary To test the effects of the treatments on smoking urges, withdrawal symptoms, and reinforcing effects of smoking. To test the effects of the treatments on methadone treatment outcomes, including retention in methadone maintenance, methadone dose changes, and continued use of illicit drugs as measured by urine toxicologies. OUTLINE: This is a multicenter study. Patients are stratified based on gender and level of nicotine dependence. Patients are randomized to 1 of 3 intervention arms. At baseline, all patients receive a minimal behavioral intervention using a 3-minute, simple smoking cessation counseling strategy, a self-help manual, and a telephone quit-line number. Arm I (varenicline): Patients receive oral varenicline once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. Arm II (placebo): Patients receive oral varenicline placebo once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. Arm III (nicotine patch/gum): Patients receive a nicotine patch, with doses tapering over time for a total of 26 weeks. Patients also receive nicotine gum to quell breakthrough urges. Patients may stop treatment when a comfortable level of smoking abstinence is reached. Patients complete a brief interview over 10-15 minutes at 2 weeks and monthly during months 1-5. They complete a longer interview over 45 minutes at months 6 and 12 and provide breath samples (for carbon monoxide monitoring) and urine samples (for cotinine testing). NOTE: Smoking cessation may prevent certain smoking-related illnesses, including cancer. PROJECTED ACCRUAL: A total of 602 patients (258 receiving varenicline, 258 receiving nicotine replacement therapy, and 86 receiving placebo) will be accrued for this study.

Official Title
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Varenicline Versus Nicotine Replacement for Methadone-Maintained Smokers

Conditions
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Bladder Cancer, Cervical Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Cancer, Kidney Cancer, Leukemia, Liver Cancer, Lung Cancer, Pancreatic Cancer, Tobacco Use Disorder

Intervention / Treatment
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* Drug: nicotine
* Drug: varenicline
* Other: placebo


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Current and regular cigarette smokers (over 10 cigarettes/day for the past 3 months) Interested in quitting smoking Willing to set a quit date 7 days after baseline assessment Participating in 1 of 5 methadone maintenance treatment programs across Rhode Island at any of the following institutions: Codac, Inc. (with two independent sites) Addiction Recovery Institute Center for Treatment and Recovery Discovery House Has received methadone for at least the past month EXCLUSION CRITERIA Pregnant or nursing (Must have negative pregnancy test) Non-English speaking No personal telephone or does not live close to a relative or neighbor with a telephone Unwilling to make their methadone dose and methadone maintenance treatment program urine toxicologies available for review Unvailable for this study for the next 12 months Suffering from any unstable medical condition which would preclude the use of the nicotine patch (e.g., unstable angina or uncontrolled hypertension) Active skin condition (e.g., psoriasis) History of skin allergy History of a suicide attempt Working as pilots, drivers, or operators of heavy machinery PRIOR CONCURRENT THERAPY: See Disease Characteristics No concurrent insulin or blood thinners No concurrent smokeless tobacco, nicotine replacement therapy, or other smoking cessation treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I<br>Patients receive oral varenicline once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. | Drug: varenicline<br>* Given orally<br>|
| Placebo Comparator: Arm II<br>Patients receive oral varenicline placebo once daily on days 1-3 and twice daily thereafter for a total of 6 months or when a comfortable level of smoking abstinence is reached. | Other: placebo<br>* Given orally<br>|
| Active Comparator: Arm III<br>Patients receive a nicotine patch, with doses tapering over time for a total of 26 weeks. Patients also receive nicotine gum to quell breakthrough urges. Patients may stop treatment when a comfortable level of smoking abstinence is reached. | Drug: nicotine<br>* Given transdermally and orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Self- Reported 7-day Abstinence | Number of participants with self-reported, 7-day abstinence at 6-months | 6 Months | 
| Carbon Monoxide (CO)-Confirmed 7-day Abstinence | Number of participants reporting 7-day abstinence at 6-months, confirmed with CO measurement. | 6-Months | 
| Rates of Smoking Cessation Continuous From First Quit Day to 6 Months | Number of participants who self-reported continuous abstinence from their initial quit day (study day 14) to 6 Months | 6-Months | 
| Self-reported 7-day Abstinence | Number of participants with self-reported 7-day abstinence at 12-months | 12 Months | 
| CO-confirmed 7-day Abstinence | Number of participants reporting 7-day abstinence at 12-months, confirmed with CO measurement. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Smoking Urges | Smoking urges was measured on a 0 (not at all) - 100 (strongest feeling possible) scale. Higher values represent greater urge to smoke. Change in smoking urges was calculated as Follow-up score (6 month) - Baseline Score. | 6 months | 
| Withdrawal Symptoms | Withdrawal Symptoms were measured using a modified version of the Minnesota Behavior Rating Scale. The scale asked subjects to rate their smoking withdrawal symptoms over the previous 24 hours on a scale from 0 (none) to 4 (severe). Higher values indicate more severe withdrawal symptoms. Change in withdrawal symptoms was calculated as Follow-up score (6 month) - Baseline Score. | 6 months | 
| Retention in Methadone Maintenance |  | 12 months | 
| Methadone Dose Changes |  | 12 months | 
| Use of Illicit Drugs as Measured by Urine Toxicologies |  | 12 months | 
| Reinforcing Effects of Smoking | Reinforcing effects of smoking was measured using the modified version of the Cigarette Evaluation Questionnaire. Participants were asked to indicate on a 12-item scale how smoking made them feel in the prior 30 days on a scale from 1 (Not at all) to 7 (Extremely). Higher values indicated that smoking was a more positive experience for 10 of 12 items. Two items were reverse coded. Change in reinforcing effects of smoking was calculated as Follow-up score (6 month) - Baseline Score. | 6 months | 
| Change in Cigarettes Per Day | Change in mean cigarettes per day | 6-Months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bladder cancer, cervical cancer, esophageal cancer, gastric cancer, renal cell carcinoma, adult primary liver cancer, non-small cell lung cancer, small cell lung cancer, pancreatic cancer, hypopharyngeal cancer, laryngeal cancer, lip and oral cavity cancer, nasopharyngeal cancer, oropharyngeal cancer, paranasal sinus and nasal cavity cancer, adult acute myeloid leukemia, tobacco use disorder