A Trial of Directly Observed and Long-term Varenicline

NCT03365362 | Completed Phase 4 DMC FDA Drug

• 2 other identifiers: 2016-6688R01DA042813
• Study Type: interventional
• Target: 243
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Tobacco Use Disorder; Opioid-use Disorder

Keywords

directly observed therapy; varenicline; long-term pharmacotherapy

Outcome Measures

Primary Outcomes (3)

• Time-to-initial abstinence

  Time-to-initial abstinence, defined as a 24 hour period without smoking, will be assessed as Period of ≥ 24 hour self-reported abstinence during the intervention period, will be assessed. Group mean time-to-initial abstinence will be reported.

  Up to 24 weeks

• Time-to-lapse

  Time-to-lapse, defined as the initial occasion of cigarette smoking after abstinence, will be based on the first day during which subjects smoke, even a puff, after a period of initial abstinence. Group mean number of days to time-to-lapse will be reported.

  Up to 24 weeks

• Time to relapse

  Time-to-relapse, defined as the return to regular cigarette use, will be based on the time first day of seven consecutive days of self-reported smoking after a period of initial abstinence. Group mean number of days to time-to-relapse will be reported.

  Up to 24 weeks

Secondary Outcomes (5)

• Durability of 7-day point prevalence tobacco abstinence

  week 28

• Durability of 7-day point prevalence tobacco abstinence

  week 52

• Number of Cigarettes smoked per day

  24 weeks

• Nicotine dependence

  24 weeks

• Quality of life - Physical and Mental Health (SF-36)

  24 weeks

Study Arms (4)

Long-Term Varenicline

EXPERIMENTAL

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

Short-Term Varenicline

ACTIVE COMPARATOR

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

Directly Observed Therapy

EXPERIMENTAL

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

Self Administered Therapy

ACTIVE COMPARATOR

Patients receiving varenicline self administered therapy (SAT) will self-administer all varenicline doses.

Behavioral: Self Administered Therapy

Interventions

Long-Term Varenicline DRUG

Varenicline tablet x 24 weeks

Also known as: varenicline, chantix

Long-Term Varenicline

Short-Term Varenicline DRUG

varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet

Also known as: varenicline, chantix, placebo

Short-Term Varenicline

Directly Observed Therapy BEHAVIORAL

Varenicline doses are administered by opioid treatment program nurses

Directly Observed Therapy

Self Administered Therapy BEHAVIORAL

Varenicline doses are self-administered

Self Administered Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \) 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.

You may not qualify if:

• \) 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.

Sponsors & Collaborators

• Albert Einstein College of Medicine: lead
• National Institutes of Health (NIH): collaborator
• Pfizer: collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Albert Einstein College of Medicine

The Bronx, New York, 10467, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Opioid-Related Disorders; Directly Observed Therapy

Interventions

Varenicline

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Narcotic-Related Disorders; Medication Adherence; Patient Compliance; Patient Acceptance of Health Care; Treatment Adherence and Compliance; Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines

Study Officials

• Shadi Nahvi, MD, MS

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2017
• First Posted: December 7, 2017
• Study Start: October 25, 2018
• Primary Completion: November 14, 2023
• Study Completion: April 24, 2024
• Last Updated: August 30, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: 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.

Locations

US (1)