A Trial of Directly Observed and Long-term Varenicline

Tobacco Use Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03365362
• Other study ID #: 2016-6688
• Secondary ID: R01DA042813
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: October 25, 2018
• Est. completion date: May 17, 2024

Study information

• Verified date: February 2024
• Source: Albert Einstein College of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 243
• Est. completion date: May 17, 2024
• Est. primary completion date: November 14, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Opioid-Related Disorders
• Opioid-use Disorder
• Tobacco Use Disorder

Intervention

Drug:
• Long-Term Varenicline
Varenicline tablet x 24 weeks
• Short-Term Varenicline
varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet

Behavioral:
• Directly Observed Therapy
Varenicline doses are administered by opioid treatment program nurses
• Self Administered Therapy
Varenicline doses are self-administered

Locations

Country	Name	City	State
United States	Albert Einstein College of Medicine	Bronx	New York

Sponsors (4)

Lead Sponsor	Collaborator
Albert Einstein College of Medicine	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Pfizer

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Initial abstinence	Period of = 24 hour self-reported abstinence during the intervention period	24 weeks
Primary	Time to lapse	First day on which subjects smoke, even a puff, after a period of initial abstinence	24 weeks
Primary	Time to relapse	First day of seven consecutive days of self-reported smoking after a period of initial abstinence	24 weeks
Secondary	Durability of tobacco abstinence	CO-verified, 7-day point prevalence abstinence at week 28	week 28
Secondary	Durability of tobacco abstinence	CO-verified, 7-day point prevalence abstinence at week 52	week 52
Secondary	Cigarettes smoked per day	self reported number of cigarettes smoked per day	24 weeks
Secondary	Nicotine dependence	Fagerstrom test of nicotine dependence	24 weeks
Secondary	Quality of life	Medical Outcomes Study Short Form 12	24 weeks