Tobacco Use DisorderPhase 4NCT03365362
A Trial of Directly Observed and Long-term Varenicline
A Phase 4 study testing Long-Term Varenicline, Short-Term Varenicline and Directly Observed Therapy in people with Tobacco Use Disorder and Opioid-use Disorder, run by Albert Einstein College of Medicine at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tobacco Use Disorder, Opioid-use Disorder
- What is being tested?
- Long-Term Varenicline, Short-Term Varenicline and Directly Observed Therapy
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 243 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Oct 2018to 24 Apr 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Albert Einstein College of Medicine
The Bronx, New York, 10467
About this study
Official title: 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.
Read the 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.
- Conditions
- Tobacco Use Disorder, Opioid-use Disorder
- Being tested
- Long-Term Varenicline, Short-Term Varenicline, Directly Observed Therapy, Self Administered Therapy
- Keywords
- directly observed therapy, varenicline, long-term pharmacotherapy
- Medical subject headings
- Tobacco Use Disorder, Opioid-Related Disorders, Directly Observed Therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Long-Term VareniclineDrug
Also called varenicline, chantix
Varenicline tablet x 24 weeks
Short-Term VareniclineDrug
Also called varenicline, chantix, placebo
varenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet
Directly Observed TherapyBehavioural
Varenicline doses are administered by opioid treatment program nurses
Self Administered TherapyBehavioural
Varenicline doses are self-administered
| Study group | Role | What they receive |
|---|---|---|
| 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) Receives: 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. Receives: 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. Receives: Behavioral: Directly Observed Therapy |
| Self Administered Therapy | Active comparator | Patients receiving varenicline self administered therapy (SAT) will self-administer all varenicline doses. Receives: Behavioral: Self Administered Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Up to 24 weeks
Secondary outcomes (5)
Durability of 7-day point prevalence tobacco abstinence
Durability of tobacco abstinence will be assessed using Carbon Monoxide (CO)-verified, 7-day point prevalence abstinence at week 28. Smoking abstinence in accordance with self-reported Timeline Follow Back Method (TLFB), which uses calendar prompts to assess self-reported daily patterns, and verified by expired carbon monoxide (CO) < 8 ppm, will be reported.
Measured: week 28
Durability of 7-day point prevalence tobacco abstinence
Durability of tobacco abstinence will be assessed using Carbon Monoxide (CO)-verified, 7-day point prevalence abstinence at week 52. Smoking abstinence in accordance with self-reported Timeline Follow Back Method (TLFB), which uses calendar prompts to assess self-reported daily patterns, and verified by expired carbon monoxide (CO) < 8 ppm, will be reported.
Measured: week 52
Number of Cigarettes smoked per day
Group mean of self-reported number of cigarettes smoked per day will be obtained via self-reported TLFB and summarized per group.
Measured: 24 weeks
Nicotine dependence
Nicotine dependence will be assessed using Fagerström Test of Nicotine Dependence (FTND). FTND is a 6-item instrument designed to provide an ordinal measure of nicotine dependence related to cigarette smoking. Specifically, the FTND evaluates the quantity of cigarette consumption, the compulsion to use, and dependence. Three Yes/No items are scored as either 0 (No) or 1 (Yes). Two multiple-choice items are either scored from 0-3 or 1-3, with higher scores signifying greater nicotine dependence. A final question, "Which cigarette would you hate to give up?" with 'First in the Morning' scored as 1 and 'Any other' scored as 0. The FTND yields an overall score of 0-10. An overall score of 1-2 = "Lowest Dependence", 3-4 = "Low to Moderate Dependence", 5-7 = "Moderate Dependence", and 8+ = "High Dependence"
Measured: 24 weeks
Quality of life - Physical and Mental Health (SF-36)
Quality of Life will be assessed using the Medical Outcomes Study Short Form 12 (SF-12). The SF-12 is a 12-item general health questionnaire, derived from the Medical Outcomes Study 36 item Short Form Survey (SF-36), is designed to have similar performance as the SF-36, while taking less time to complete. The SF-12 asks a series of questions measuring eight health domains assessing both physical (PCS-12) and mental health (MCS-12). Two summary scores are generated: a mental component score (MCS-12), and a physical component score (PCS-12). Scores for both range from 0-100 with higher scores indicating better physical and mental health functioning, respectively. A score of 50 or less on the PCS-12 has been recommended as a cut-off to determine a physical condition, while a score of 42 or less on the MCS-12 may be indicative of 'clinical depression'. Group mean scores will be reported.
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Dec 2017
- Study start25 Oct 2018
- Primary completion14 Nov 2023
- Study completion24 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Tobacco Use DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 243 participants (actual)
Sponsor and investigators
- Lead sponsor
- Albert Einstein College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), Pfizer, National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Shadi Nahvi, MD, MS, Principal investigator, Albert Einstein College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03365362
- Sponsor's protocol ID
- 2016-6688
- Other IDs
- R01DA042813
- Status last verified
- Aug 2024
- First submitted
- 28 Nov 2017
- Last updated
- 30 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Achieving Smoking Cessation Milestones in Opioid Treatment Patients: a Randomized 2 x 2 Factorial Trial of Directly Observed and Long-term Varenicline
- ClinicalTrials.gov ID
- NCT03365362
- Acronym / sponsor ID
- 2016-6688
- Conditions
- Tobacco Use Disorder, Opioid-use Disorder
- Keywords
- directly observed therapy, varenicline, long-term pharmacotherapy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 243 participants (actual)
- Lead sponsor
- Albert Einstein College of MedicineUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), Pfizer, National Institute on Drug Abuse (NIDA)
- Study start
- 25 Oct 2018 (actual)
- Primary completion
- 14 Nov 2023 (actual)
- Study completion
- 24 Apr 2024 (actual)
- First posted
- 7 Dec 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Long-Term Varenicline | Experimental | Drug: Long-Term VareniclineParticipants 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) |
| Short-Term Varenicline | Active comparator | Drug: Short-Term VareniclineParticipants 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. |
| Directly Observed Therapy | Experimental | Behavioral: Directly Observed TherapyParticipants 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. |
| Self Administered Therapy | Active comparator | Behavioral: Self Administered TherapyPatients receiving varenicline self administered therapy (SAT) will self-administer all varenicline doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Long-Term VareniclineAlso: varenicline, chantixVarenicline tablet x 24 weeks | Drug | Long-Term Varenicline |
| Short-Term VareniclineAlso: varenicline, chantix, placebovarenicline tablet for 12 weeks, followed by placebo tablet manufactured to mimic varenicline 1 mg tablet | Drug | Short-Term Varenicline |
| Directly Observed TherapyVarenicline doses are administered by opioid treatment program nurses | Behavioural | Directly Observed Therapy |
| Self Administered TherapyVarenicline doses are self-administered | Behavioural | Self Administered Therapy |
Primary outcome
Time-to-initial abstinence
Time frame: Up to 24 weeks
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.
Time-to-lapse
Time frame: Up to 24 weeks
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.
Time to relapse
Time frame: Up to 24 weeks
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.
5 secondary outcomes
Durability of 7-day point prevalence tobacco abstinence
Time frame: week 28
Durability of 7-day point prevalence tobacco abstinence
Time frame: week 52
Number of Cigarettes smoked per day
Time frame: 24 weeks
Nicotine dependence
Time frame: 24 weeks
Quality of life - Physical and Mental Health (SF-36)
Time frame: 24 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2024.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shadi Nahvi, MD, MS principal investigator
Albert Einstein College of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Long-Term Varenicline, Short-Term Varenicline and Directly Observed Therapy in people with Tobacco Use Disorder and Opioid-use Disorder, run by Albert Einstein College of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time-to-initial abstinence (time frame: Up to 24 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2024.