A Trial of Directly Observed and Long-term Varenicline

Sponsor

Albert Einstein College of Medicine (Other)

Overall Status

Recruiting

CT.gov ID

NCT03365362

Collaborator

National Institutes of Health (NIH) (NIH), Pfizer (Industry), National Institute on Drug Abuse (NIDA) (NIH)

450

Enrollment

Location

Arms

54.2

Anticipated Duration (Months)

8.3

Patients Per Site Per Month

Study Details

Study Description

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 450 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.

Condition or Disease	Intervention/Treatment	Phase
Tobacco Use Disorder Opioid-use Disorder	Drug: Long-Term Varenicline Drug: Short-Term Varenicline Behavioral: Directly Observed Therapy Behavioral: Self Administered Therapy	Phase 4

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 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

450 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Achieving Smoking Cessation Milestones in Opioid Treatment Patients: a Randomized 2 x 2 Factorial Trial of Directly Observed and Long-term Varenicline

Actual Study Start Date :

Oct 25, 2018

Anticipated Primary Completion Date :

Sep 1, 2022

Anticipated Study Completion Date :

May 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Long-Term Varenicline Participants will receive 24 weeks of varenicline at standard doses (0.5 mg/day for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily)	Drug: Long-Term Varenicline Varenicline tablet x 24 weeks Other Names: varenicline chantix
Active Comparator: Short-Term Varenicline Participants will receive 12 weeks of varenicline at standard doses (0.5 mg/day for days 1 to 3, 0.5 mg twice daily for days 4 to 7, then 1 mg twice daily), followed by matching placebo twice daily through week 24.	Drug: Short-Term Varenicline varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet Other Names: varenicline chantix placebo
Experimental: Directly Observed Therapy Participants receiving directly observed therapy (DOT) will receive varenicline from opioid treatment program nurses at the same time as they receive methadone, as well as individually packaged take-home doses for self administration on evenings/weekends.	Behavioral: Directly Observed Therapy Varenicline doses are administered by opioid treatment program nurses
Active Comparator: Self Administered Therapy Patients receiving varenicline self administered therapy (SAT) will self-administer all varenicline doses.	Behavioral: Self Administered Therapy Varenicline doses are self-administered

Outcome Measures

Primary Outcome Measures

Initial abstinence [24 weeks]
Period of ≥ 24 hour self-reported abstinence during the intervention period
Time to lapse [24 weeks]
First day on which subjects smoke, even a puff, after a period of initial abstinence
Time to relapse [24 weeks]
First day of seven consecutive days of self-reported smoking after a period of initial abstinence

Secondary Outcome Measures

Durability of tobacco abstinence [week 28]
CO-verified, 7-day point prevalence abstinence at week 28
Durability of tobacco abstinence [week 52]
CO-verified, 7-day point prevalence abstinence at week 52
Cigarettes smoked per day [24 weeks]
self reported number of cigarettes smoked per day
Nicotine dependence [24 weeks]
Fagerstrom test of nicotine dependence
Quality of life [24 weeks]
Medical Outcomes Study Short Form 12

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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;
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:

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.