Cigarette Smoking, Methadone Maintenance
Conditions
Keywords
Cigarette, Methadone, Smoking, Cessation, Varenicline, Nicotine
Brief summary
The objective is to provide a preliminary test of the ability of two pharmacological treatments, the nicotine nasal spray and varenicline, relative to placebos, to reduce smoking during the 4 hours following methadone dosing.
Detailed description
Smoking prevalence is over 83% in methadone-maintained patients. These patients experience significant difficulty quitting, and there is evidence that a majority of methadone-maintained patients smoke most of their cigarettes in the 4 hours following methadone dosing. The objective is to provide a preliminary test of the ability of two pharmacological treatments, the nicotine nasal spray and varenicline, relative to placebos, to reduce smoking during the 4 hours following methadone dosing.
Interventions
7 days. 1 mg/dose, up to 40x/day.
DRUGVarenicline
14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily.
DRUGPlacebo Nasal Spray
7 days. 1 mg/dose, up to 40x/day.1 mg/dose, up to 40x/day. This will appear similar to the Nicotine Nasal Spray, but will be a placebo.
14 days. Days 1-3: 0.5 mg once daily; Days 4-7: 0.5 mg twice daily; Days 8-14: 1 mg twice daily. This will appear identical to the drug Varenicline, but will be a placebo.
Sponsors
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. be male or female, 18 years of age or older 2. be able to understand the study, and having understood, provide written informed consent in English 3. have been enrolled in the University of Cincinnati Physicians Company-Opioid Treatment Program (UCPC-OTP) program for at least 30 days and be stable on the current methadone dose for at least 1 week 4. have smoked cigarettes for at least 3 months, have a measured exhaled carbon monoxide (CO) level \> 8 parts per million (ppm), and not planning to seek smoking-cessation treatment within the next 3 months 5. have a willingness to comply with all study procedures, including trying to stop smoking during designated weeks, and to comply with medication instructions 6. based on a week of Quitbit cigarette lighter assessments, with at least 5 days of usable data, smoke ≥ 10 cigarettes/day and smoke at least 30% of daily cigarettes within the 4-hour post-methadone-dosing period 7. if female and of child bearing potential, agree to use one of the following methods of birth control: oral contraceptives, contraceptive patch, barrier (diaphragm or condom), intrauterine contraceptive system, levonorgestrel implant, medroxyprogesterone acetate contraceptive injection,complete abstinence from sexual intercourse, hormonal vaginal contraceptive ring.
Exclusion criteria
1. have a current or past diagnosis of any psychotic disorder, or bipolar I or II disorder 2. have a psychiatric condition that, in the judgment of the study physician would make study participation unsafe or which would make treatment compliance difficult 3. be a significant suicidal/homicidal risk 4. have a medical condition that, in the judgment of the study physician, would make study participation unsafe or which would make treatment compliance difficult. Such conditions include, but are not limited to: * liver function tests greater than 3 times upper limit of normal * serum creatinine greater than 2 mg/dL 5. have had clinically significant cardiovascular or cerebrovascular disease within the past 6 months or have clinically significant ECG abnormalities 6. have taken an investigational drug within 30 days before consent 7. be taking concomitant medications that are contraindicated for use with the NNS or varenicline 8. be taking any concomitant medications that could increase the likelihood of smoking cessation (such as wellbutrin or nortriptyline) 9. have a known or suspected hypersensitivity to varenicline or the nicotine nasal spray (NNS) 10. use/have used smoking-cessation counseling programs with individual counseling or smoking-cessation medication treatments currently, or within 30 days before consent 11. have used electronic cigarettes or tobacco products, other than cigarettes, in the week before consent 12. be pregnant or breastfeeding 13. be anyone who, in the judgment of the investigator, would not be expected to complete the study protocol (e.g., due to relocation from the clinic area, probable incarceration, etc.)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose | 7 weeks | Subjects will be given a special electronic cigarette lighter called Quitbit.The electronic lighter will record a timestamp for each time the lighter is used to light a cigarette. Data will be collected from the lighter at each study visit. This will measure how many cigarettes are smoked and when. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cigarettes Per Day | 7 weeks | The Quitbit lighter will measure how many cigarettes are smoked per day. In addition to the Quitbit lighter measurement, the Timeline Follow Back (TLFB) form will be filled out for each subject to measure use, as well. |
| Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | up to 8 weeks | Carbon monoxide (CO) in each participant's breath will be tested. A CO level less than or equal to 8 parts-per-million will be used to verify reports of no smoking. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants randomized in this crossover trial (each randomized participant was intended to receive each medication) | 7 |
| Total | 7 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 37.9 years STANDARD_DEVIATION 8.4 |
| Current Methadone Dose | 109.9 milligrams STANDARD_DEVIATION 35 |
| Fagerström Test for Nicotine Dependence | 5.3 units on a scale STANDARD_DEVIATION 1 |
| Race/Ethnicity, Customized Race, Ethnicity Other, Non-Hispanic | 1 Participants |
| Race/Ethnicity, Customized Race, Ethnicity White, Non-Hispanic | 6 Participants |
| Region of Enrollment United States | 7 participants |
| Sex: Female, Male Female | 4 Participants |
| Sex: Female, Male Male | 3 Participants |
| Years in Methadone Treatment | 3.1 years STANDARD_DEVIATION 3.6 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
| other Total, other adverse events | 4 / 7 | 1 / 7 | 2 / 6 | 0 / 6 |
| serious Total, serious adverse events | 0 / 7 | 0 / 7 | 0 / 6 | 0 / 6 |
Outcome results
Primary
Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose
Subjects will be given a special electronic cigarette lighter called Quitbit.The electronic lighter will record a timestamp for each time the lighter is used to light a cigarette. Data will be collected from the lighter at each study visit. This will measure how many cigarettes are smoked and when.
Time frame: 7 weeks
Population: Varenicline and placebo varenicline analysis populations are less than 7 because 1 participant was lost to follow-up and provided no data for these assigned medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Nasal Spray | Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose | 0.294 proportion of daily cigarettes | Standard Deviation 0.13 |
| Placebo Nasal Spray | Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose | 0.177 proportion of daily cigarettes | Standard Deviation 0.104 |
| Varenicline Tablets | Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose | 0.196 proportion of daily cigarettes | Standard Deviation 0.088 |
| Placebo Varenicline Tablets | Proportion of Daily Cigarettes Smoked in the 4 Hours After Receiving Methadone Dose | 0.325 proportion of daily cigarettes | Standard Deviation 0.346 |
Secondary
Cigarettes Per Day
The Quitbit lighter will measure how many cigarettes are smoked per day. In addition to the Quitbit lighter measurement, the Timeline Follow Back (TLFB) form will be filled out for each subject to measure use, as well.
Time frame: 7 weeks
Population: Varenicline and placebo varenicline analysis populations are less than 7 because 1 participant was lost to follow-up and provided no data for these assigned medications.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Nicotine Nasal Spray | Cigarettes Per Day | 13.7 cigarettes per day | Standard Deviation 6.4 |
| Placebo Nasal Spray | Cigarettes Per Day | 15.8 cigarettes per day | Standard Deviation 8.2 |
| Varenicline Tablets | Cigarettes Per Day | 12.5 cigarettes per day | Standard Deviation 12.8 |
| Placebo Varenicline Tablets | Cigarettes Per Day | 9.0 cigarettes per day | Standard Deviation 6.9 |
Secondary
Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million
Carbon monoxide (CO) in each participant's breath will be tested. A CO level less than or equal to 8 parts-per-million will be used to verify reports of no smoking.
Time frame: up to 8 weeks
Population: Varenicline and placebo varenicline analysis populations are less than 7 because 1 participant was lost to follow-up and provided no data for these assigned medications.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nicotine Nasal Spray | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO less than or equal to 8 ppm | 2 Participants |
| Nicotine Nasal Spray | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO greater than 8 ppm | 5 Participants |
| Placebo Nasal Spray | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO greater than 8 ppm | 6 Participants |
| Placebo Nasal Spray | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO less than or equal to 8 ppm | 1 Participants |
| Varenicline Tablets | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO less than or equal to 8 ppm | 3 Participants |
| Varenicline Tablets | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO greater than 8 ppm | 3 Participants |
| Placebo Varenicline Tablets | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO less than or equal to 8 ppm | 2 Participants |
| Placebo Varenicline Tablets | Number of Participants With Carbon Monoxide Levels Less Than or Equal to 8 Parts-per-million | Participants with CO greater than 8 ppm | 4 Participants |