A Trial of Directly Observed and Long-term Varenicline

• ClinicalTrials.gov Identifier: NCT03365362
• Recruitment Status: Recruiting
• First Posted: December 7, 2017
• Last Update Posted: October 22, 2020
• Sponsor: Albert Einstein College of Medicine
• Collaborators: National Institutes of Health (NIH); Pfizer; National Institute on Drug Abuse (NIDA)
• Information provided by (Responsible Party): Shadi Nahvi, Albert Einstein College of Medicine

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 (Clinical Trial)
• Estimated 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: October 25, 2018
• Estimated Primary Completion Date: September 2022
• Estimated Study Completion Date: May 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 :

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

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Contacts

Contact: Shadi Nahvi, MD, MS; 718 920 5379; snahvi@montefiore.org

Locations

United States, New York

Albert Einstein College of Medicine of Yeshiva University; Recruiting

Bronx, New York, United States, 10467

Principal Investigator: Shadi Nahvi, M.D., M.S.

Sponsors and Collaborators

Albert Einstein College of Medicine

National Institutes of Health (NIH)

Pfizer

National Institute on Drug Abuse (NIDA)

Investigators

• Principal Investigator: Shadi Nahvi, MD, MS; Albert Einstein College of Medicine

More Information

• Responsible Party: Shadi Nahvi, Principal Investigator, Albert Einstein College of Medicine
• ClinicalTrials.gov Identifier: NCT03365362
• Other Study ID Numbers: 2016-6688; R01DA042813 ( U.S. NIH Grant/Contract )
• First Posted: December 7, 2017
• Last Update Posted: October 22, 2020
• Last Verified: October 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Analytic Code
• Time Frame: After data collection and cleaning is complete.
• 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.

• 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

Keywords provided by Shadi Nahvi, Albert Einstein College of Medicine:

directly observed therapy; varenicline; long-term pharmacotherapy

Additional relevant MeSH terms:

Disease; Tobacco Use Disorder; Pathologic Processes; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Varenicline; Nicotinic Agonists; Cholinergic Agonists; Cholinergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs