Medication Adherence, Tobacco Use Disorder
Conditions
Keywords
Smoking, Substance-Related Disorders, medication adherence, Methadone
Brief summary
This randomized trial will evaluate whether varenicline directly observed therapy provided at a methadone clinic is more efficacious than self-administered varenicline for promoting smoking cessation and enhancing adherence.
Detailed description
There is a marked prevalence of tobacco use and tobacco-related disease among methadone maintenance patients. Varenicline's demonstrated efficacy may not be generalizable to methadone maintained smokers because of poor adherence, which is highly prevalent among drug users. Adherence to smoking cessation medication is strongly associated with cessation, and is one of the few factors shown to increase cessation among methadone maintained smokers, but strategies to promote smoking cessation medication adherence have not been evaluated in methadone patients. Based on the Information, Motivation, and Behavior model, the investigators plan a directly observed therapy (DOT)-based intervention targeting behavioral skills necessary for optimal adherence. Because methadone clinic-based DOT interventions have been shown to improve medication adherence and clinical outcomes in HIV and TB, the investigators plan to determine in a randomized trial whether DOT varenicline provided at a methadone clinic is more efficacious than self-administered varenicline for promoting smoking cessation and enhancing adherence. The investigators will also evaluate moderating effects of drug and alcohol use and psychiatric symptoms on DOT effects. The investigators hypothesize subjects in the mDOT arm will have greater 7 day point prevalence abstinence at 12 weeks, reduction in cigarettes/day, time to first daily cigarette, ≥ 24 hour quit attempts, and 7 day point prevalence abstinence at 24 weeks compared to subjects receiving self administered varenicline. The investigators also hypothesize that adherence in the mDOT arm will be higher than in the TAU arm. Lastly the investigators hypothesize that ongoing illicit drug use and psychiatric symptoms will moderate the effect of mDOT on adherence.
Interventions
DRUGVarenicline
Varenicline, titrated to 1 mg twice daily, will be given to participants in both study arms for 12 weeks.
Sponsors
National Institute on Drug Abuse (NIDA)
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * English speaking * Smoked at least 100 cigarettes/lifetime * Smoke 5 or more cigarettes per day * Interested in quitting smoking (preparation or contemplation stage of change) * Enrolled in Einstein/Montefiore methadone program for 12 weeks or more * Receiving methadone in clinic three, four, five or six times per week * No more than 2 methadone clinic misses in prior 14 days * Agree to use contraception for the duration of the trial (among women with reproductive potential) * Willing to participate in all study components * Able to provide informed consent
Exclusion criteria
* Serious or unstable HIV/AIDS, liver, cardiovascular, or pulmonary disease * Psychiatric instability * Women who are pregnant, breastfeeding, or contemplating pregnancy * Creatinine clearance \<30 mL/min
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Varenicline Adherence as Measured by Pill Count | Weeks 0-1, 1-2, 2-3, 4-6, 7-9, 10-12 | Pill count adherence, measured as pills taken divided by pills dispensed, analyzed as a continuous measure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 12 Weeks | Week 12 of treatment | Number of participants achieving self reported, seven day point prevalence abstinence, biochemically verified with expired carbon monoxide (CO) \< 8 p.p.m., missing = smoking |
| Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 24 Weeks | 24 weeks | Number of participants achieving self reported, seven day point prevalence abstinence, biochemically verified with expired carbon monoxide (CO) \< 8 p.p.m. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Varenicline Treatment as Usual (TAU) Subjects in the TAU arm will self administer varenicline for 12 weeks.
Varenicline: Varenicline, titrated to 1 mg twice daily, will be given to participants in both study arms for 12 weeks. | 50 |
| Varenicline Directly Observed Therapy Subjects in the directly observed therapy (DOT) arm will receive varenicline directly administered by methadone clinic nurses 4-6 times per week at the same time as they receive methadone, as well as individually packaged take-home doses for self administration on evenings/weekends.
Varenicline: Varenicline, titrated to 1 mg twice daily, will be given to participants in both study arms for 12 weeks. | 50 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Total | Varenicline Treatment as Usual (TAU) | Varenicline Directly Observed Therapy |
|---|---|---|---|
| Age, Continuous | 49 years | 49 years | 49 years |
| Any past quit attempts | 81 participants | 39 participants | 42 participants |
| Cigarettes smoked per day | 10 cigarettes smoked per day | 10 cigarettes smoked per day | 12 cigarettes smoked per day |
| Currently receiving psychiatric treatment | 37 Participants | 19 Participants | 18 Participants |
| Expired carbon monoxide | 7 parts per million | 7 parts per million | 8 parts per million |
| Fagerstrom Test of Nicotine Dependence score | 5 units on a scale | 5 units on a scale | 5 units on a scale |
| Ladder of change score | 8 units on a scale | 8 units on a scale | 8 units on a scale |
| Lifetime major depressive episode | 21 Participants | 10 Participants | 11 Participants |
| Lifetime psychotic disorder | 10 Participants | 6 Participants | 4 Participants |
| Lifetime suicide attempt | 15 Participants | 7 Participants | 8 Participants |
| Median duration methadone maintenance | 5.6 years | 5 years | 5.6 years |
| Median methadone dose | 90 mg | 92 mg | 83.5 mg |
| Number of participants currently employed | 20 Participants | 10 Participants | 10 Participants |
| Number of participants married or living with a partner | 45 Participants | 19 Participants | 26 Participants |
| Number of participants with unstable housing | 64 participants | 27 participants | 37 participants |
| Participants with COPD/Asthma | 30 Participants | 15 Participants | 15 Participants |
| Participants with HIV/AIDS | 20 Participants | 9 Participants | 11 Participants |
| Preferred brand of cigarettes menthol | 88 Participants | 46 Participants | 42 Participants |
| Quit confidence | 8 units on a scale | 7 units on a scale | 8 units on a scale |
| Quit importance | 10 units on a scale | 10 units on a scale | 10 units on a scale |
| Race/Ethnicity, Customized Black | 30 Participants | 13 Participants | 17 Participants |
| Race/Ethnicity, Customized Hispanic | 44 Participants | 22 Participants | 22 Participants |
| Race/Ethnicity, Customized Mutliracial/multiethnic | 10 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized Other | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 14 Participants | 7 Participants | 7 Participants |
| Severe global psychiatric symptoms | 17 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Female | 44 Participants | 20 Participants | 24 Participants |
| Sex: Female, Male Male | 56 Participants | 30 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 |
| other Total, other adverse events | 50 / 50 | 50 / 50 |
| serious Total, serious adverse events | 2 / 50 | 3 / 50 |
Outcome results
Primary
Varenicline Adherence as Measured by Pill Count
Pill count adherence, measured as pills taken divided by pills dispensed, analyzed as a continuous measure
Time frame: Weeks 0-1, 1-2, 2-3, 4-6, 7-9, 10-12
Population: Comparison of varenicline TAU and DOT groups
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Varenicline Treatment as Usual (TAU) | Varenicline Adherence as Measured by Pill Count | 61.8 percentage pills taken/pills dispensed |
| Varenicline Directly Observed Therapy | Varenicline Adherence as Measured by Pill Count | 78.5 percentage pills taken/pills dispensed |
Secondary
Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 12 Weeks
Number of participants achieving self reported, seven day point prevalence abstinence, biochemically verified with expired carbon monoxide (CO) \< 8 p.p.m., missing = smoking
Time frame: Week 12 of treatment
Population: intent to treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Treatment as Usual (TAU) | Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 12 Weeks | 9 Participants |
| Varenicline Directly Observed Therapy | Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 12 Weeks | 5 Participants |
Secondary
Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 24 Weeks
Number of participants achieving self reported, seven day point prevalence abstinence, biochemically verified with expired carbon monoxide (CO) \< 8 p.p.m.
Time frame: 24 weeks
Population: Missing = smoking
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Varenicline Treatment as Usual (TAU) | Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 24 Weeks | 6 Participants |
| Varenicline Directly Observed Therapy | Tobacco Abstinence Biochemically Verified With Expired Carbon Monoxide (CO) < 8 p.p.m. at 24 Weeks | 2 Participants |