ClinicalTrials.gov
ClinicalTrials.gov Menu

A Trial of Directly Observed and Long-term Varenicline

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03365362
Recruitment Status : Not yet recruiting
First Posted : December 7, 2017
Last Update Posted : August 22, 2018
Sponsor:
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, Inc.

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 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
Estimated Study Start Date : September 2018
Estimated Primary Completion Date : September 2021
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine


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




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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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 five 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03365362


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
Bronx, New York, United States, 10467
Sponsors and Collaborators
Albert Einstein College of Medicine, Inc.
National Institutes of Health (NIH)
Pfizer
National Institute on Drug Abuse (NIDA)
Investigators
Principal Investigator: Shadi Nahvi, MD, MS Albert Einstein College of Medicine, Inc.

Responsible Party: Shadi Nahvi, Principal Investigator, Albert Einstein College of Medicine, Inc.
ClinicalTrials.gov Identifier: NCT03365362     History of Changes
Other Study ID Numbers: 2016-6688
R01DA042813 ( U.S. NIH Grant/Contract )
First Posted: December 7, 2017    Key Record Dates
Last Update Posted: August 22, 2018
Last Verified: August 2018
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, Inc.:
directly observed therapy
varenicline
long-term pharmacotherapy

Additional relevant MeSH terms:
Tobacco Use Disorder
Disease
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