Tobacco Use Disorder, Opioid-use Disorder
Conditions
Keywords
directly observed therapy, varenicline, long-term pharmacotherapy
Brief summary
This 2 x 2 factorial, randomized, double-blind, placebo-controlled trial will test two interventions: directly observed medication therapy, and long-term therapy with varenicline among smokers with opioid use disorder recruited from community-based, outpatient opioid treatment programs. The analytic strategy will evaluate the milestones in smoking cessation-achieving initial abstinence, preventing lapse and preventing relapse--necessary for long-term cessation, and evaluate theoretically-guided psychological and social factors and pharmacogenetic factors that influence these cessation processes.
Detailed description
Tobacco use and tobacco-related disease are highly prevalent among persons with opioid use disorders (OUD). Unfortunately, traditional evidence-based smoking cessation interventions have yielded low rates of tobacco abstinence in this group. The majority of trials evaluating smoking cessation treatment interventions among persons with OUD have relied on short-term interventions that do not account for the unique challenges faced by these smokers, specifically, establishing initial abstinence, adhering to evidence-based cessation treatments, and maintaining abstinence once active treatments cease. Long-term smoking cessation medication treatment approaches have shown promise in promoting cessation and decreasing relapse among individuals without OUD, however the applicability of extended medication approaches to smokers with OUD may be limited by poor adherence to smoking cessation medications. Though adherence to cessation medication is strongly associated with cessation success, adherence is especially challenging for persons with OUD. Opioid treatment program-based directly observed therapy (DOT) interventions improve clinical outcomes in HIV and TB, and pilot data suggest that DOT varenicline is associated with increased smoking cessation medication adherence and may increase smoking cessation rates. In this 2 x 2 factorial, randomized, double-blind, placebo-controlled trial, the investigators will test two interventions: directly observed medication therapy, and long-term therapy with varenicline. The analytic strategy will evaluate the milestones in smoking cessation-achieving initial abstinence, preventing lapse and preventing relapse--necessary for long-term cessation, and evaluate theoretically-guided psychological and social factors and pharmacogenetic factors that influence these cessation processes. The investigators will recruit smokers with OUD from community-based, outpatient opioid treatment programs and test the following specific aims: (1) to test the efficacy of directly observed varenicline therapy compared to self-administered varenicline therapy on smoking cessation milestones, (2) to test the efficacy of long-term varenicline compared to short-term varenicline on smoking cessation milestones, and (3) to understand the mechanism of smoking cessation by examining the impact of theory-guided psychological and social factors and of pharmacogenetic factors on cessation milestones.
Interventions
DRUGLong-Term Varenicline
Varenicline tablet x 24 weeks
DRUGShort-Term Varenicline
varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet
BEHAVIORALDirectly Observed Therapy
Varenicline doses are administered by opioid treatment program nurses
BEHAVIORALSelf Administered Therapy
Varenicline doses are self-administered
Sponsors
National Institutes of Health (NIH)
Pfizer
National Institute on Drug Abuse (NIDA)
Albert Einstein College of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1\) age ≥18 years old; 2) English or Spanish speaking (i.e., be able to participate in study interviews in English or Spanish); 3) current cigarette smoking (smoked at least 100 cigarettes/lifetime, smoking ≥ 5 cigarettes/day); 4) interest in quitting tobacco smoking; 5) receiving methadone or buprenorphine in the DoSA clinic one to six times weekly; 6) enrollment in a DoSA opioid treatment program ≥ 3 months; 7) stable methadone or buprenorphine dose for two weeks; 8) agreement to use contraception for the duration of the trial (among women with reproductive potential); 9) willingness to participate in all study components; and 10) ability to provide informed consent.
Exclusion criteria
1\) serious or unstable disease, specifically: decompensated cirrhosis (INR≥ 1.7, albumin \<2.7 g/dl or physical exam evidence of decompensated cirrhosis); severe cardiovascular disease (MI, PTCA, unstable angina, CABG, and/or serious arrhythmia in the previous 6 months); severe asthma or chronic obstructive pulmonary disease (requiring supplemental oxygen or hospitalization in past 6 months); HIV/AIDS (AIDS-defining illness or hospitalization in past 6 months); 2) creatinine clearance \<30 mL/min; 3) history of seizure disorder; 4) women who are pregnant, breastfeeding, or contemplating pregnancy; 5) current suicidal ideation; 6) history of suicide attempt in the past year; 7) psychiatric hospitalization in the past year; 8) current DSM V criteria for major depressive episode, current bipolar disorder, or current psychotic disorder; 9) current DSM V criteria for alcohol use disorder; or 10) use of varenicline in the past 30 days.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time-to-initial abstinence | Up to 24 weeks | Time-to-initial abstinence, defined as a 24 hour period without smoking, will be assessed as Period of ≥ 24 hour self-reported abstinence during the intervention period, will be assessed. Group mean time-to-initial abstinence will be reported. |
| Time-to-lapse | Up to 24 weeks | Time-to-lapse, defined as the initial occasion of cigarette smoking after abstinence, will be based on the first day during which subjects smoke, even a puff, after a period of initial abstinence. Group mean number of days to time-to-lapse will be reported. |
| Time to relapse | Up to 24 weeks | Time-to-relapse, defined as the return to regular cigarette use, will be based on the time first day of seven consecutive days of self-reported smoking after a period of initial abstinence. Group mean number of days to time-to-relapse will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Durability of 7-day point prevalence tobacco abstinence | week 28 | Durability of tobacco abstinence will be assessed using Carbon Monoxide (CO)-verified, 7-day point prevalence abstinence at week 28. Smoking abstinence in accordance with self-reported Timeline Follow Back Method (TLFB), which uses calendar prompts to assess self-reported daily patterns, and verified by expired carbon monoxide (CO) \< 8 ppm, will be reported. |
| Quality of life - Physical and Mental Health (SF-36) | 24 weeks | Quality of Life will be assessed using the Medical Outcomes Study Short Form 12 (SF-12). The SF-12 is a 12-item general health questionnaire, derived from the Medical Outcomes Study 36 item Short Form Survey (SF-36), is designed to have similar performance as the SF-36, while taking less time to complete. The SF-12 asks a series of questions measuring eight health domains assessing both physical (PCS-12) and mental health (MCS-12). Two summary scores are generated: a mental component score (MCS-12), and a physical component score (PCS-12). Scores for both range from 0-100 with higher scores indicating better physical and mental health functioning, respectively. A score of 50 or less on the PCS-12 has been recommended as a cut-off to determine a physical condition, while a score of 42 or less on the MCS-12 may be indicative of 'clinical depression'. Group mean scores will be reported. |
| Number of Cigarettes smoked per day | 24 weeks | Group mean of self-reported number of cigarettes smoked per day will be obtained via self-reported TLFB and summarized per group. |
| Nicotine dependence | 24 weeks | Nicotine dependence will be assessed using Fagerström Test of Nicotine Dependence (FTND). FTND is a 6-item instrument designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. Specifically, the FTND evaluates the quantity of cigarette consumption, the compulsion to use, and dependence. Three Yes/No items are scored as either 0 (No) or 1 (Yes). Two multiple-choice items are either scored from 0-3 or 1-3, with higher scores signifying greater nicotine dependence. A final question, Which cigarette would you hate to give up? with 'First in the Morning' scored as 1 and 'Any other' scored as 0. The FTND yields an overall score of 0-10. An overall score of 1-2 = Lowest Dependence, 3-4 = Low to Moderate Dependence, 5-7 = Moderate Dependence, and 8+ = High Dependence |
Countries
United States
Outcome results
None listed