A Trial of Directly Observed and Long-term Varenicline

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Tobacco Use Disorder; Opioid-use Disorder
• Intervention / Treatment: Drug: Long-Term Varenicline; Drug: Short-Term Varenicline; Behavioral: Directly Observed Therapy; Behavioral: Self Administered Therapy

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.

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Shadi Nahvi, MD, MS; Phone Number: 718 920 5379; Email: snahvi@montefiore.org

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Albert Einstein College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / 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: placebo; varenicline; chantix
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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institute on Drug Abuse (NIDA); Pfizer; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Shadi Nahvi, MD, MS, Albert Einstein College of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2018
• Primary Completion (Actual): November 14, 2023
• Study Completion (Estimated): May 17, 2024

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 6, 2017
• First Posted (Actual): December 7, 2017

Study Record Updates

• Last Update Posted (Estimated): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: varenicline; directly observed therapy; long-term pharmacotherapy
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Narcotic-Related Disorders; Tobacco Use Disorder; Opioid-Related Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Nicotinic Agonists; Cholinergic Agonists; Varenicline
• Other Study ID Numbers: 2016-6688; R01DA042813 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Our final dataset will include: survey and laboratory data, including demographic, medical, tobacco, and other substance use-related information about all clinical trial subjects. The final dataset will be stripped of all personal identifiers.
• IPD Sharing Time Frame: After data collection and cleaning is complete.
• IPD Sharing Access Criteria: We will share data with qualified investigators whose research protocols have been approved by their institutions' Institutional Review Boards. Data will be made available to potential users under a NIDA-approved data-sharing agreement that ensures that: (1) data is used only for research purposes and does not identify individual participants; (2) data is handled in a secure and confidential way; and (3) data is destroyed or returned after analyses are completed.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes