Bladder Cancer, Cervical Cancer, Esophageal Cancer, Gastric Cancer, Head and Neck Cancer, Kidney Cancer, Leukemia, Liver Cancer, Lung Cancer, Pancreatic Cancer, Tobacco Use Disorder
Conditions
Keywords
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
Brief summary
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
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.
Interventions
DRUGnicotine
Given transdermally and orally
DRUGvarenicline
Given orally
OTHERplacebo
Given orally
Sponsors
National Cancer Institute (NCI)
Butler Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Self- Reported 7-day Abstinence | 6 Months | Number of participants with self-reported, 7-day abstinence at 6-months |
| Carbon Monoxide (CO)-Confirmed 7-day Abstinence | 6-Months | Number of participants reporting 7-day abstinence at 6-months, confirmed with CO measurement. |
| Rates of Smoking Cessation Continuous From First Quit Day to 6 Months | 6-Months | Number of participants who self-reported continuous abstinence from their initial quit day (study day 14) to 6 Months |
| Self-reported 7-day Abstinence | 12 Months | Number of participants with self-reported 7-day abstinence at 12-months |
| CO-confirmed 7-day Abstinence | 12 Months | Number of participants reporting 7-day abstinence at 12-months, confirmed with CO measurement. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reinforcing Effects of Smoking | 6 months | 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. |
| Change in Smoking Urges | 6 months | 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. |
| Change in Cigarettes Per Day | 6-Months | Change in mean cigarettes per day |
| Withdrawal Symptoms | 6 months | 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. |
| Retention in Methadone Maintenance | 12 months | — |
| Methadone Dose Changes | 12 months | — |
| Use of Illicit Drugs as Measured by Urine Toxicologies | 12 months | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm I 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.
varenicline: Given orally | 137 |
| Arm II 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.
placebo: Given orally | 45 |
| Arm III 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.
nicotine: Given transdermally and orally | 133 |
| Total | 315 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| End of Study (12 Month Interview) | Lost to Follow-up | 66 | 19 | 50 |
| End of Treatment (6 Month Interview) | Death | 0 | 2 | 1 |
| End of Treatment (6 Month Interview) | Hospitalized | 2 | 0 | 0 |
| End of Treatment (6 Month Interview) | Incarcerated | 0 | 0 | 3 |
| End of Treatment (6 Month Interview) | Lost to Follow-up | 20 | 8 | 20 |
| End of Treatment (6 Month Interview) | Residential Treatment | 0 | 0 | 2 |
Baseline characteristics
| Characteristic | Total | Arm I | Arm II | Arm III |
|---|---|---|---|---|
| Age, Continuous | 39.9 years STANDARD_DEVIATION 9.7 | 39.2 years STANDARD_DEVIATION 9.7 | 40.6 years STANDARD_DEVIATION 10.6 | 40.3 years STANDARD_DEVIATION 9.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 38 Participants | 17 Participants | 4 Participants | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 277 Participants | 120 Participants | 41 Participants | 116 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 2 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 19 Participants | 5 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 38 Participants | 17 Participants | 4 Participants | 17 Participants |
| Race (NIH/OMB) White | 250 Participants | 113 Participants | 34 Participants | 103 Participants |
| Region of Enrollment United States | 315 participants | 137 participants | 45 participants | 133 participants |
| Sex: Female, Male Female | 159 Participants | 74 Participants | 17 Participants | 68 Participants |
| Sex: Female, Male Male | 156 Participants | 63 Participants | 28 Participants | 65 Participants |
| Years of Education | 11.8 years STANDARD_DEVIATION 1.9 | 11.8 years STANDARD_DEVIATION 2 | 11.4 years STANDARD_DEVIATION 1.9 | 11.9 years STANDARD_DEVIATION 2.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 137 | 0 / 45 | 0 / 133 |
| serious Total, serious adverse events | 4 / 137 | 2 / 45 | 2 / 133 |
Outcome results
Primary
Carbon Monoxide (CO)-Confirmed 7-day Abstinence
Number of participants reporting 7-day abstinence at 6-months, confirmed with CO measurement.
Time frame: 6-Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Carbon Monoxide (CO)-Confirmed 7-day Abstinence | 5 participants |
| Arm II | Carbon Monoxide (CO)-Confirmed 7-day Abstinence | 1 participants |
| Arm III | Carbon Monoxide (CO)-Confirmed 7-day Abstinence | 11 participants |
Primary
CO-confirmed 7-day Abstinence
Number of participants reporting 7-day abstinence at 12-months, confirmed with CO measurement.
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | CO-confirmed 7-day Abstinence | 4 participants |
| Arm II | CO-confirmed 7-day Abstinence | 1 participants |
| Arm III | CO-confirmed 7-day Abstinence | 8 participants |
Primary
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
Time frame: 6-Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Rates of Smoking Cessation Continuous From First Quit Day to 6 Months | 2 participants |
| Arm II | Rates of Smoking Cessation Continuous From First Quit Day to 6 Months | 0 participants |
| Arm III | Rates of Smoking Cessation Continuous From First Quit Day to 6 Months | 2 participants |
Primary
Self-reported 7-day Abstinence
Number of participants with self-reported 7-day abstinence at 12-months
Time frame: 12 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Self-reported 7-day Abstinence | 4 participants |
| Arm II | Self-reported 7-day Abstinence | 3 participants |
| Arm III | Self-reported 7-day Abstinence | 11 participants |
Primary
Self- Reported 7-day Abstinence
Number of participants with self-reported, 7-day abstinence at 6-months
Time frame: 6 Months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I | Self- Reported 7-day Abstinence | 11 participants |
| Arm II | Self- Reported 7-day Abstinence | 3 participants |
| Arm III | Self- Reported 7-day Abstinence | 16 participants |
Secondary
Change in Cigarettes Per Day
Change in mean cigarettes per day
Time frame: 6-Months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Change in Cigarettes Per Day | -8.7 cigarettes/day | Standard Deviation 9.2 |
| Arm II | Change in Cigarettes Per Day | -8.5 cigarettes/day | Standard Deviation 9.5 |
| Arm III | Change in Cigarettes Per Day | -7.8 cigarettes/day | Standard Deviation 9.4 |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Change in Smoking Urges | -29.971 units on a scale | Standard Deviation 39.12 |
| Arm II | Change in Smoking Urges | -25.015 units on a scale | Standard Deviation 31.689 |
| Arm III | Change in Smoking Urges | -24.177 units on a scale | Standard Deviation 37.015 |
Secondary
Methadone Dose Changes
Time frame: 12 months
Population: Data not collected
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Reinforcing Effects of Smoking | -1.005 units on a scale | Standard Deviation 1.173 |
| Arm II | Reinforcing Effects of Smoking | -.683 units on a scale | Standard Deviation 0.865 |
| Arm III | Reinforcing Effects of Smoking | -.761 units on a scale | Standard Deviation 0.957 |
Secondary
Retention in Methadone Maintenance
Time frame: 12 months
Population: Data not collected
Secondary
Use of Illicit Drugs as Measured by Urine Toxicologies
Time frame: 12 months
Population: Data not collected
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm I | Withdrawal Symptoms | -.222 units on a scale | Standard Deviation 0.618 |
| Arm II | Withdrawal Symptoms | -.163 units on a scale | Standard Deviation 0.447 |
| Arm III | Withdrawal Symptoms | -.113 units on a scale | Standard Deviation 0.564 |