A Trial of Directly Observed and Long-term Varenicline

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 450 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.

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 five 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.