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Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

Sponsor
Northwestern University (Other)
Overall Status
Completed
CT.gov ID
NCT02378714
Collaborator
National Cancer Institute (NCI) (NIH)
300
Enrollment
2
Locations
4
Arms
55.7
Actual Duration (Months)
150
Patients Per Site
2.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Persons who struggle with depression smoke at high rates and experience low quit rates in treatment. The best way to improve cessation treatment for this underserved population remains unknown. The proposed trial tests whether the combination of varenicline and behavioral mood management treatment enhances long-term abstinence for depressed smokers and, if so, whether this treatment achieves its effects through addressing the unique psychological factors that appear to maintain tobacco dependence for these smokers.

Condition or Disease Intervention/Treatment Phase
Phase 4

Detailed Description

Upwards of 43% of persons with major depressive disorder (MDD) are daily smokers who are more likely to smoke heavily, show greater tobacco dependence, suffer more severe withdrawal, and experience lower quit rates than smokers without MDD. Little is known about treatment strategies that might optimize smoking cessation for smokers with MDD because almost all randomized clinical trials have excluded these smokers. This project answers many prominent but largely unanswered calls over the last decade to address tobacco dependence in persons with mental health disorders, especially major depressive disorder (MDD). Using a double-blind, placebo-controlled, randomized design, the investigators will evaluate the efficacy of behavioral activation for smoking cessation (BASC) plus varenicline for treating tobacco dependence in smokers with current or lifetime MDD. Three hundred and thirty daily (≥1 cigarettes/day) smokers will be randomized to receive 12 weeks of one of four treatments:

  1. Standard behavioral cessation treatment (ST) + placebo; 2) Behavioral activation integrated with ST (BASC) + placebo; 3) ST + varenicline; or 4) BASC + varenicline. Both BASC and ST will be administered in eight 45 minute sessions, occurring weekly for the first four weeks and biweekly for the final eight weeks. Randomization will be stratified on clinical site (Northwestern, University of Pennsylvania), gender, and severity of depressive symptoms (minimal/mild vs. moderate/severe). The primary outcomes will be carbon monoxide (CO) verified 7-day point prevalence abstinence at 24-weeks post-quit. Additional aims include assessing adverse event rates between varenicline and placebo arms, and testing for mediation of treatment effects by anhedonia, cognitive function (attention and memory), cigarette reward value, and craving and withdrawal. This randomized controlled trial will be the first adequately powered trial of BASC in this population; the first trial to evaluate varenicline among a community sample of smokers with MDD; and the first trial to assess the main and combined effects of these two treatments.

Study Design

Study Type:
Interventional
Actual Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers
Actual Study Start Date :
Jul 24, 2015
Actual Primary Completion Date :
Mar 13, 2020
Actual Study Completion Date :
Mar 13, 2020

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Standard treatment + placebo varenicline

Standard behavioral smoking cessation treatment plus placebo varenicline

Behavioral: Standard treatment
Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
Other Names:
  • Standard Therapy

    		•
    Experimental: BASC + placebo varenicline

    Behavioral activation for smoking cessation plus placebo varenicline

    Behavioral: BASC
    The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Other Names:
  • Behavioral activation for smoking cessation

    		•
    Active Comparator: Standard treatment + active varenicline

    Standard behavioral smoking cessation treatment plus active varenicline

    Drug: Varenicline
    Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.
    Other Names:
  • Chantix

    • Behavioral: Standard treatment
    Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Other Names:
  • Standard Therapy

    		•
    Experimental: BASC + active varenicline

    Behavioral activation for smoking cessation plus active varenicline

    Drug: Varenicline
    Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.
    Other Names:
  • Chantix

    • Behavioral: BASC
    The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Other Names:
  • Behavioral activation for smoking cessation

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Bioverified Point-prevalence Abstinence at 27 Weeks [27 weeks (24-weeks post-target quit date)]

      Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 27 (24 weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 27.

    2. Adverse Event and Serious Adverse Event Rates [Weeks 1 (1-week before starting medication), 6, and 14 (end of medication)]

      Adverse event and serious adverse event rates between varenicline and placebo arms. A previously developed algorithm was used to classify side effect reports as adverse events (AEs) or serious adverse events (SAEs) (Schnoll et al. 2019). Reference: Schnoll, R., Leone, F., Weisbrot, J., Veluz-Wilkins, A., Miele, A., Hole, A., Jao, N.C., Wileyto, E.P., Carroll, A.J., Kalhan, R., Patel, J., Langer, C., & Hitsman, B. (2019). A randomized controlled trial of 24-weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Psycho-Oncology, 28, 561-569.

    Secondary Outcome Measures

    1. Bioverified Point-prevalence Abstinence at 14 Weeks (End of Treatment) [14 weeks (11-weeks post-target quit date)]

      Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 14 (11-weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 14.

    2. Prolonged Abstinence [27 weeks (24 weeks post target quit date)]

      <7 consecutive days of self-reported smoking after a 2-week grace period

    3. Continuous Abstinence [27 weeks (24 weeks post target quit date)]

      No smoking between target quit date (week 3) and week 27

    4. Time to 7-day Relapse [27 weeks (24 weeks post target quit date)]

      Time to relapse as defined by 7 or more consecutive days of self-reported smoking (no grace period)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion criteria:

    1. adult (18 years of age or older) daily cigarette smokers (1+ cigarettes per day)

    2. meet criteria for current or lifetime MDD without psychotic features

    3. have or are willing to acquire a personal email address and access to a camera phone or other method for submission of therapy practice assignments

    4. speak, read, and write fluently in English

    5. able to provide written informed consent

    6. intend to reside in the geographic area for >8 months

    7. women of childbearing potential must agree to use a medically acceptable method of birth control or abstain from sexual intercourse during the time they are taking study medication and for at least one month after the medication period ends.

    8. The candidate had to answer "yes" to the question: "Are you interested in quitting smoking?"

    Exclusion criteria:

    1. current enrollment or plan to enroll in another smoking cessation program in the next 8 months

    2. regular (daily) use of e-cigarettes, chewing tobacco, snuff, snus, or other tobacco products

    3. current use or plan to use nicotine replacement therapy or other smoking cessation medication within the next 8 months

    4. medications indicated for bipolar or psychotic disorder if prescribed for bipolar or psychotic disorder

    5. pregnant or planning to become pregnant within the next 8 months, or breast feeding

    6. history of seizures or current seizure disorder without medication

    7. history of severe (stage IV or V) chronic kidney disease including current or prior end stage renal disease on either hemodialysis or peritoneal dialysis or prior renal transplant

    8. any prior solid organ transplant or prior hematopoietic stem cell transplant

    9. alcohol consumption exceeding 28 drinks per week

    10. cirrhosis or end-stage liver disease

    11. systolic blood pressure >185 mmHg or diastolic blood pressure >110 mmHg after two readings or symptomatic uncontrolled stage II hypertension

    12. unstable cardiovascular disease within 3 months prior to baseline or other cardiovascular disease requiring hospitalization

    13. prior hospitalization for heart failure

    14. previous allergic reaction to varenicline

    15. high suicide risk based on the Columbia Suicide Severity Rating Scale

    16. lifetime bipolar or psychotic disorder as determined by either self-report or clinical interview

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Northwestern University Chicago Illinois United States 60611
    2 University of Pennsylvania Philadelphia Pennsylvania United States 19104

    Sponsors and Collaborators

    • Northwestern University
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Brian Hitsman, Ph.D., Northwestern University

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    Brian Hitsman, Associate Professor of Preventive Medicine, Northwestern University
    ClinicalTrials.gov Identifier:
    NCT02378714
    Other Study ID Numbers:
    • STU00100303
    • 1R01CA184211-01A1
    First Posted:
    Mar 4, 2015
    Last Update Posted:
    Jul 29, 2021
    Last Verified:
    May 1, 2021
    Keywords provided by Brian Hitsman, Associate Professor of Preventive Medicine, Northwestern University
    Smoking Cessation
    Major Depressive Disorder
    Nicotine Dependence
    Varenicline
    Behavioral Activation Therapy
    Cigarette Smoking
    Additional relevant MeSH terms:
    Tobacco Use Disorder
    Depressive Disorder
    Depression
    Depressive Disorder, Major
    Varenicline

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Period Title: Overall Study
    STARTED 68 68 81 83
    COMPLETED 39 29 51 51
    NOT COMPLETED 29 39 30 32

    Baseline Characteristics

    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline Total
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Total of all reporting groups
    Overall Participants 68 68 81 83 300
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    63
    92.6%
    58
    85.3%
    74
    91.4%
    75
    90.4%
    270
    90%
    >=65 years
    5
    7.4%
    10
    14.7%
    7
    8.6%
    8
    9.6%
    30
    10%
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    50.3
    (10.8)
    50.7
    (13.5)
    48.7
    (12.7)
    50.3
    (13.2)
    50.0
    (12.6)
    Sex: Female, Male (Count of Participants)
    Female
    39
    57.4%
    38
    55.9%
    44
    54.3%
    44
    53%
    165
    55%
    Male
    29
    42.6%
    30
    44.1%
    37
    45.7%
    39
    47%
    135
    45%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    1
    1.2%
    1
    1.2%
    2
    0.7%
    Asian
    0
    0%
    1
    1.5%
    3
    3.7%
    0
    0%
    4
    1.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    40
    58.8%
    37
    54.4%
    43
    53.1%
    37
    44.6%
    157
    52.3%
    White
    25
    36.8%
    27
    39.7%
    28
    34.6%
    36
    43.4%
    116
    38.7%
    More than one race
    1
    1.5%
    3
    4.4%
    4
    4.9%
    8
    9.6%
    16
    5.3%
    Unknown or Not Reported
    2
    2.9%
    0
    0%
    2
    2.5%
    1
    1.2%
    5
    1.7%
    Region of Enrollment (participants) [Number]
    United States
    68
    100%
    68
    100%
    81
    100%
    83
    100%
    300
    100%

    Outcome Measures

    1. Primary Outcome
    Title Bioverified Point-prevalence Abstinence at 27 Weeks
    Description Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 27 (24 weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 27.
    Time Frame 27 weeks (24-weeks post-target quit date)

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the trial (intent-to-treat sample)
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Measure Participants 68 68 81 83
    Count of Participants [Participants]
    6
    8.8%
    3
    4.4%
    13
    16%
    13
    15.7%
    2. Primary Outcome
    Title Adverse Event and Serious Adverse Event Rates
    Description Adverse event and serious adverse event rates between varenicline and placebo arms. A previously developed algorithm was used to classify side effect reports as adverse events (AEs) or serious adverse events (SAEs) (Schnoll et al. 2019). Reference: Schnoll, R., Leone, F., Weisbrot, J., Veluz-Wilkins, A., Miele, A., Hole, A., Jao, N.C., Wileyto, E.P., Carroll, A.J., Kalhan, R., Patel, J., Langer, C., & Hitsman, B. (2019). A randomized controlled trial of 24-weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Psycho-Oncology, 28, 561-569.
    Time Frame Weeks 1 (1-week before starting medication), 6, and 14 (end of medication)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Placebo - Week 1 Varenicline - Week 1 Placebo - Week 6 Varenicline - Week 6 Placebo - Week 14 Varenicline - Week 14
    Arm/Group Description Placebo group during first week of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group during first week of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group mid-treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group mid-treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at end of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at end of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.
    Measure Participants 136 164 91 121 74 104
    Any adverse event
    104
    152.9%
    136
    200%
    68
    84%
    81
    97.6%
    50
    16.7%
    60
    NaN
    Any serious adverse event
    28
    41.2%
    34
    50%
    26
    32.1%
    22
    26.5%
    9
    3%
    8
    NaN
    3. Secondary Outcome
    Title Bioverified Point-prevalence Abstinence at 14 Weeks (End of Treatment)
    Description Participants were classified as abstinent if they reported abstinence, not even a puff of a cigarette, for >7 days prior to week 14 (11-weeks post-target quit date) and had an expired carbon monoxide reading of ≤ 6 parts per million at week 14.
    Time Frame 14 weeks (11-weeks post-target quit date)

    Outcome Measure Data

    Analysis Population Description
    All participants enrolled in the trial (intent-to-treat sample)
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Measure Participants 68 68 81 83
    Count of Participants [Participants]
    8
    11.8%
    4
    5.9%
    26
    32.1%
    26
    31.3%
    4. Secondary Outcome
    Title Prolonged Abstinence
    Description <7 consecutive days of self-reported smoking after a 2-week grace period
    Time Frame 27 weeks (24 weeks post target quit date)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Measure Participants 57 45 68 70
    Count of Participants [Participants]
    13
    19.1%
    11
    16.2%
    26
    32.1%
    26
    31.3%
    5. Secondary Outcome
    Title Continuous Abstinence
    Description No smoking between target quit date (week 3) and week 27
    Time Frame 27 weeks (24 weeks post target quit date)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Measure Participants 59 52 72 71
    Count of Participants [Participants]
    3
    4.4%
    2
    2.9%
    6
    7.4%
    2
    2.4%
    6. Secondary Outcome
    Title Time to 7-day Relapse
    Description Time to relapse as defined by 7 or more consecutive days of self-reported smoking (no grace period)
    Time Frame 27 weeks (24 weeks post target quit date)

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Standard Treatment + Placebo Varenicline BASC + Placebo Varenicline Standard Treatment + Active Varenicline BASC + Active Varenicline
    Arm/Group Description Standard behavioral smoking cessation treatment plus placebo varenicline Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus placebo varenicline BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Standard behavioral smoking cessation treatment plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Standard treatment: Standard behavioral smoking cessation treatment is an effective treatment for nicotine dependence. Treatment focuses on self-monitoring of smoking behavior, identifying smoking triggers and alternative trigger management strategies, relaxation, social support for non-smoking, and relapse prevention. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions. Behavioral activation for smoking cessation plus active varenicline Varenicline: Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. BASC: The goal of behavioral activation therapy is to increase engagement in rewarding activities, a problem for smokers with depression who find smoking especially rewarding and prefer it over many other traditionally rewarding activities, by reducing patterns of behavioral avoidance, withdrawal, and inactivity. In this study, behavioral activation will be integrated with standard behavioral smoking cessation treatment. Treatment will be delivered in eight 45-minute sessions over 12 weeks occurring weekly for the first four sessions and biweekly for the final four sessions.
    Measure Participants 57 45 68 70
    Median (95% Confidence Interval) [median days to relapse]
    15
    15
    57
    24

    Adverse Events

    Time Frame Medication side effects were measured using a 28-item side effect checklist rating scale at week 1 (1 week before starting medication), week 3 (target quit day) through 14, and week 27.
    Adverse Event Reporting Description Adverse events and serious adverse events are reported only for active and placebo medication arms, which aligns with our primary aim for varenicline safety and the statistical analysis plan.
    Arm/Group Title Placebo - Week 1 Varenicline - Week 1 Placebo - Week 3 Varenicline - Week 3 Placebo - Week 4 Varenicline - Week 4 Placebo - Week 6 Varenicline - Week 6 Placebo - Week 7 Varenicline - Week 7 Placebo - Week 8 Varenicline - Week 8 Placebo - Week 10 Varenicline - Week 10 Placebo - Week 12 Varenicline - Week 12 Placebo - Week 14 Varenicline - Week 14 Placebo - Week 27 Varenicline - Week 27
    Arm/Group Description Placebo group during first week of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group during first week of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 3. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 3. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 4. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 4. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group mid-treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group mid-treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 7. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 7. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 8. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 8. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 10. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 10. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 12. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 12. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at end of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at end of treatment. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Placebo group at week 27. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment. Varenicline group at week 27. Day 1-3: 0.5mg once daily orally Day 4-7: 0.5mg twice daily orally Day 8-84: 1.0mg twice daily orally Participants will be randomly assigned to 12 weeks of either placebo or varenicline medication (1mg twice daily). Participants and research personnel will be blind to treatment assignment.
    All Cause Mortality
    Placebo - Week 1 Varenicline - Week 1 Placebo - Week 3 Varenicline - Week 3 Placebo - Week 4 Varenicline - Week 4 Placebo - Week 6 Varenicline - Week 6 Placebo - Week 7 Varenicline - Week 7 Placebo - Week 8 Varenicline - Week 8 Placebo - Week 10 Varenicline - Week 10 Placebo - Week 12 Varenicline - Week 12 Placebo - Week 14 Varenicline - Week 14 Placebo - Week 27 Varenicline - Week 27
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/136 (0%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 0/100 (0%) 0/120 (0%) 0/91 (0%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Serious Adverse Events
    Placebo - Week 1 Varenicline - Week 1 Placebo - Week 3 Varenicline - Week 3 Placebo - Week 4 Varenicline - Week 4 Placebo - Week 6 Varenicline - Week 6 Placebo - Week 7 Varenicline - Week 7 Placebo - Week 8 Varenicline - Week 8 Placebo - Week 10 Varenicline - Week 10 Placebo - Week 12 Varenicline - Week 12 Placebo - Week 14 Varenicline - Week 14 Placebo - Week 27 Varenicline - Week 27
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 28/136 (20.6%) 34/164 (20.7%) 24/114 (21.1%) 29/137 (21.2%) 21/100 (21%) 19/120 (15.8%) 26/91 (28.6%) 22/121 (18.2%) 18/85 (21.2%) 18/119 (15.1%) 15/80 (18.8%) 14/115 (12.2%) 15/79 (19%) 18/113 (15.9%) 12/79 (15.2%) 12/109 (11%) 9/74 (12.2%) 8/104 (7.7%) 10/68 (14.7%) 12/102 (11.8%)
    Cardiac disorders
    Irregular heartbeat 1/136 (0.7%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 0/100 (0%) 0/120 (0%) 0/91 (0%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Increased heart rate 1/136 (0.7%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 0/100 (0%) 0/120 (0%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Gastrointestinal disorders
    Abdominal Pain 0/136 (0%) 0/164 (0%) 2/114 (1.8%) 2/137 (1.5%) 1/100 (1%) 0/120 (0%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 1/119 (0.8%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 3/113 (2.7%) 0/79 (0%) 1/109 (0.9%) 0/74 (0%) 1/104 (1%) 0/68 (0%) 0/102 (0%)
    General disorders
    Nausea 0/136 (0%) 1/164 (0.6%) 2/114 (1.8%) 3/137 (2.2%) 0/100 (0%) 0/120 (0%) 2/91 (2.2%) 1/121 (0.8%) 0/85 (0%) 2/119 (1.7%) 0/80 (0%) 0/115 (0%) 1/79 (1.3%) 3/113 (2.7%) 1/79 (1.3%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 1/68 (1.5%) 1/102 (1%)
    Headache 1/136 (0.7%) 3/164 (1.8%) 2/114 (1.8%) 1/137 (0.7%) 0/100 (0%) 1/120 (0.8%) 1/91 (1.1%) 3/121 (2.5%) 0/85 (0%) 2/119 (1.7%) 1/80 (1.3%) 1/115 (0.9%) 0/79 (0%) 2/113 (1.8%) 1/79 (1.3%) 2/109 (1.8%) 1/74 (1.4%) 2/104 (1.9%) 0/68 (0%) 1/102 (1%)
    Dizziness 0/136 (0%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 0/100 (0%) 1/120 (0.8%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 1/119 (0.8%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Skin swelling or rash 0/136 (0%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 1/100 (1%) 0/120 (0%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 1/80 (1.3%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 1/68 (1.5%) 0/102 (0%)
    skin redness 0/136 (0%) 0/164 (0%) 0/114 (0%) 0/137 (0%) 0/100 (0%) 0/120 (0%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Weakness on one or both sides of the body 1/136 (0.7%) 1/164 (0.6%) 0/114 (0%) 1/137 (0.7%) 3/100 (3%) 0/120 (0%) 2/91 (2.2%) 2/121 (1.7%) 1/85 (1.2%) 0/119 (0%) 0/80 (0%) 1/115 (0.9%) 0/79 (0%) 1/113 (0.9%) 0/79 (0%) 0/109 (0%) 1/74 (1.4%) 0/104 (0%) 0/68 (0%) 1/102 (1%)
    Chest Pain 0/136 (0%) 0/164 (0%) 0/114 (0%) 1/137 (0.7%) 0/100 (0%) 1/120 (0.8%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 0/119 (0%) 0/80 (0%) 0/115 (0%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 0/74 (0%) 0/104 (0%) 0/68 (0%) 0/102 (0%)
    Psychiatric disorders
    Depressed Mood 3/136 (2.2%) 3/164 (1.8%) 3/114 (2.6%) 4/137 (2.9%) 2/100 (2%) 4/120 (3.3%) 1/91 (1.1%) 6/121 (5%) 1/85 (1.2%) 4/119 (3.4%) 4/80 (5%) 4/115 (3.5%) 0/79 (0%) 2/113 (1.8%) 0/79 (0%) 4/109 (3.7%) 1/74 (1.4%) 2/104 (1.9%) 0/68 (0%) 0/102 (0%)
    Suicidal thoughts or i deation 4/136 (2.9%) 15/164 (9.1%) 6/114 (5.3%) 8/137 (5.8%) 3/100 (3%) 6/120 (5%) 9/91 (9.9%) 6/121 (5%) 5/85 (5.9%) 7/119 (5.9%) 5/80 (6.3%) 4/115 (3.5%) 3/79 (3.8%) 5/113 (4.4%) 3/79 (3.8%) 2/109 (1.8%) 3/74 (4.1%) 1/104 (1%) 1/68 (1.5%) 5/102 (4.9%)
    Anxiety 5/136 (3.7%) 3/164 (1.8%) 1/114 (0.9%) 3/137 (2.2%) 1/100 (1%) 4/120 (3.3%) 2/91 (2.2%) 5/121 (4.1%) 1/85 (1.2%) 3/119 (2.5%) 2/80 (2.5%) 1/115 (0.9%) 3/79 (3.8%) 3/113 (2.7%) 3/79 (3.8%) 2/109 (1.8%) 0/74 (0%) 1/104 (1%) 1/68 (1.5%) 1/102 (1%)
    Agitation 20/136 (14.7%) 19/164 (11.6%) 10/114 (8.8%) 16/137 (11.7%) 12/100 (12%) 10/120 (8.3%) 12/91 (13.2%) 9/121 (7.4%) 10/85 (11.8%) 11/119 (9.2%) 7/80 (8.8%) 10/115 (8.7%) 8/79 (10.1%) 10/113 (8.8%) 9/79 (11.4%) 7/109 (6.4%) 5/74 (6.8%) 7/104 (6.7%) 8/68 (11.8%) 4/102 (3.9%)
    Hostility 6/136 (4.4%) 8/164 (4.9%) 5/114 (4.4%) 2/137 (1.5%) 8/100 (8%) 4/120 (3.3%) 4/91 (4.4%) 5/121 (4.1%) 6/85 (7.1%) 4/119 (3.4%) 7/80 (8.8%) 3/115 (2.6%) 5/79 (6.3%) 5/113 (4.4%) 4/79 (5.1%) 5/109 (4.6%) 4/74 (5.4%) 3/104 (2.9%) 1/68 (1.5%) 3/102 (2.9%)
    Irritability 4/136 (2.9%) 1/164 (0.6%) 3/114 (2.6%) 3/137 (2.2%) 4/100 (4%) 3/120 (2.5%) 5/91 (5.5%) 4/121 (3.3%) 3/85 (3.5%) 3/119 (2.5%) 2/80 (2.5%) 1/115 (0.9%) 2/79 (2.5%) 5/113 (4.4%) 1/79 (1.3%) 1/109 (0.9%) 2/74 (2.7%) 2/104 (1.9%) 2/68 (2.9%) 1/102 (1%)
    Disturbance in Attention 2/136 (1.5%) 2/164 (1.2%) 1/114 (0.9%) 3/137 (2.2%) 1/100 (1%) 0/120 (0%) 0/91 (0%) 1/121 (0.8%) 0/85 (0%) 2/119 (1.7%) 1/80 (1.3%) 1/115 (0.9%) 0/79 (0%) 0/113 (0%) 1/79 (1.3%) 1/109 (0.9%) 0/74 (0%) 1/104 (1%) 1/68 (1.5%) 1/102 (1%)
    Other (Not Including Serious) Adverse Events
    Placebo - Week 1 Varenicline - Week 1 Placebo - Week 3 Varenicline - Week 3 Placebo - Week 4 Varenicline - Week 4 Placebo - Week 6 Varenicline - Week 6 Placebo - Week 7 Varenicline - Week 7 Placebo - Week 8 Varenicline - Week 8 Placebo - Week 10 Varenicline - Week 10 Placebo - Week 12 Varenicline - Week 12 Placebo - Week 14 Varenicline - Week 14 Placebo - Week 27 Varenicline - Week 27
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 104/136 (76.5%) 136/164 (82.9%) 90/114 (78.9%) 103/137 (75.2%) 80/100 (80%) 93/120 (77.5%) 68/91 (74.7%) 81/121 (66.9%) 65/85 (76.5%) 77/119 (64.7%) 57/80 (71.3%) 71/115 (61.7%) 51/79 (64.6%) 71/113 (62.8%) 52/79 (65.8%) 63/109 (57.8%) 50/74 (67.6%) 60/104 (57.7%) 37/68 (54.4%) 55/102 (53.9%)
    Cardiac disorders
    Irregular Heartbeat 1/136 (0.7%) 6/164 (3.7%) 0/114 (0%) 2/137 (1.5%) 3/100 (3%) 3/120 (2.5%) 4/91 (4.4%) 3/121 (2.5%) 2/85 (2.4%) 6/119 (5%) 1/80 (1.3%) 3/115 (2.6%) 1/79 (1.3%) 4/113 (3.5%) 1/79 (1.3%) 3/109 (2.8%) 2/74 (2.7%) 3/104 (2.9%) 0/68 (0%) 0/102 (0%)
    Increased heart rate or palpitations 7/136 (5.1%) 19/164 (11.6%) 7/114 (6.1%) 8/137 (5.8%) 5/100 (5%) 13/120 (10.8%) 7/91 (7.7%) 13/121 (10.7%) 4/85 (4.7%) 13/119 (10.9%) 4/80 (5%) 11/115 (9.6%) 4/79 (5.1%) 10/113 (8.8%) 5/79 (6.3%) 10/109 (9.2%) 3/74 (4.1%) 8/104 (7.7%) 2/68 (2.9%) 3/102 (2.9%)
    Gastrointestinal disorders
    Abdominal Pain 21/136 (15.4%) 23/164 (14%) 13/114 (11.4%) 28/137 (20.4%) 14/100 (14%) 28/120 (23.3%) 15/91 (16.5%) 24/121 (19.8%) 14/85 (16.5%) 21/119 (17.6%) 12/80 (15%) 21/115 (18.3%) 12/79 (15.2%) 21/113 (18.6%) 15/79 (19%) 15/109 (13.8%) 13/74 (17.6%) 11/104 (10.6%) 8/68 (11.8%) 17/102 (16.7%)
    Increased Flatulence 10/136 (7.4%) 6/164 (3.7%) 5/114 (4.4%) 8/137 (5.8%) 7/100 (7%) 10/120 (8.3%) 10/91 (11%) 16/121 (13.2%) 5/85 (5.9%) 11/119 (9.2%) 5/80 (6.3%) 11/115 (9.6%) 3/79 (3.8%) 11/113 (9.7%) 6/79 (7.6%) 5/109 (4.6%) 6/74 (8.1%) 9/104 (8.7%) 4/68 (5.9%) 4/102 (3.9%)
    Constipation 6/136 (4.4%) 5/164 (3%) 3/114 (2.6%) 4/137 (2.9%) 5/100 (5%) 5/120 (4.2%) 7/91 (7.7%) 10/121 (8.3%) 3/85 (3.5%) 8/119 (6.7%) 5/80 (6.3%) 8/115 (7%) 3/79 (3.8%) 9/113 (8%) 4/79 (5.1%) 4/109 (3.7%) 5/74 (6.8%) 5/104 (4.8%) 3/68 (4.4%) 6/102 (5.9%)
    Gastroesophageal reflux or indigestion 6/136 (4.4%) 10/164 (6.1%) 4/114 (3.5%) 11/137 (8%) 9/100 (9%) 7/120 (5.8%) 7/91 (7.7%) 9/121 (7.4%) 8/85 (9.4%) 11/119 (9.2%) 3/80 (3.8%) 7/115 (6.1%) 4/79 (5.1%) 7/113 (6.2%) 3/79 (3.8%) 5/109 (4.6%) 5/74 (6.8%) 6/104 (5.8%) 3/68 (4.4%) 7/102 (6.9%)
    Diarrhea 0/136 (0%) 3/164 (1.8%) 2/114 (1.8%) 2/137 (1.5%) 1/100 (1%) 0/120 (0%) 1/91 (1.1%) 0/121 (0%) 0/85 (0%) 1/119 (0.8%) 1/80 (1.3%) 1/115 (0.9%) 0/79 (0%) 0/113 (0%) 0/79 (0%) 0/109 (0%) 1/74 (1.4%) 1/104 (1%) 1/68 (1.5%) 0/102 (0%)
    General disorders
    Nausea 3/136 (2.2%) 7/164 (4.3%) 6/114 (5.3%) 7/137 (5.1%) 6/100 (6%) 9/120 (7.5%) 6/91 (6.6%) 6/121 (5%) 7/85 (8.2%) 7/119 (5.9%) 5/80 (6.3%) 4/115 (3.5%) 10/79 (12.7%) 1/113 (0.9%) 3/79 (3.8%) 3/109 (2.8%) 1/74 (1.4%) 3/104 (2.9%) 2/68 (2.9%) 5/102 (4.9%)
    Vomiting 8/136 (5.9%) 10/164 (6.1%) 3/114 (2.6%) 9/137 (6.6%) 3/100 (3%) 7/120 (5.8%) 3/91 (3.3%) 2/121 (1.7%) 3/85 (3.5%) 4/119 (3.4%) 2/80 (2.5%) 4/115 (3.5%) 1/79 (1.3%) 6/113 (5.3%) 5/79 (6.3%) 3/109 (2.8%) 2/74 (2.7%) 2/104 (1.9%) 2/68 (2.9%) 2/102 (2%)
    Dry Mouth 10/136 (7.4%) 16/164 (9.8%) 9/114 (7.9%) 13/137 (9.5%) 11/100 (11%) 17/120 (14.2%) 5/91 (5.5%) 10/121 (8.3%) 6/85 (7.1%) 12/119 (10.1%) 4/80 (5%) 7/115 (6.1%) 3/79 (3.8%) 7/113 (6.2%) 5/79 (6.3%) 5/109 (4.6%) 7/74 (9.5%) 1/104 (1%) 3/68 (4.4%) 2/102 (2%)
    Skin swelling or rash 10/136 (7.4%) 7/164 (4.3%) 7/114 (6.1%) 1/137 (0.7%) 7/100 (7%) 6/120 (5%) 5/91 (5.5%) 6/121 (5%) 4/85 (4.7%) 5/119 (4.2%) 6/80 (7.5%) 3/115 (2.6%) 4/79 (5.1%) 3/113 (2.7%) 5/79 (6.3%) 0/109 (0%) 8/74 (10.8%) 5/104 (4.8%) 3/68 (4.4%) 4/102 (3.9%)
    Headache 6/136 (4.4%) 15/164 (9.1%) 8/114 (7%) 9/137 (6.6%) 7/100 (7%) 7/120 (5.8%) 8/91 (8.8%) 9/121 (7.4%) 4/85 (4.7%) 10/119 (8.4%) 4/80 (5%) 5/115 (4.3%) 1/79 (1.3%) 5/113 (4.4%) 4/79 (5.1%) 5/109 (4.6%) 1/74 (1.4%) 5/104 (4.8%) 3/68 (4.4%) 5/102 (4.9%)
    Dizziness 15/136 (11%) 20/164 (12.2%) 9/114 (7.9%) 17/137 (12.4%) 11/100 (11%) 9/120 (7.5%) 11/91 (12.1%) 12/121 (9.9%) 10/85 (11.8%) 13/119 (10.9%) 7/80 (8.8%) 11/115 (9.6%) 6/79 (7.6%) 11/113 (9.7%) 6/79 (7.6%) 6/109 (5.5%) 8/74 (10.8%) 4/104 (3.8%) 4/68 (5.9%) 9/102 (8.8%)
    Fatigue/lethargy 36/136 (26.5%) 41/164 (25%) 20/114 (17.5%) 20/137 (14.6%) 18/100 (18%) 23/120 (19.2%) 15/91 (16.5%) 18/121 (14.9%) 15/85 (17.6%) 13/119 (10.9%) 7/80 (8.8%) 17/115 (14.8%) 12/79 (15.2%) 13/113 (11.5%) 7/79 (8.9%) 12/109 (11%) 9/74 (12.2%) 11/104 (10.6%) 6/68 (8.8%) 10/102 (9.8%)
    Feeling of weakness without loss of strength 12/136 (8.8%) 14/164 (8.5%) 4/114 (3.5%) 6/137 (4.4%) 7/100 (7%) 7/120 (5.8%) 4/91 (4.4%) 8/121 (6.6%) 3/85 (3.5%) 4/119 (3.4%) 2/80 (2.5%) 3/115 (2.6%) 1/79 (1.3%) 4/113 (3.5%) 0/79 (0%) 6/109 (5.5%) 4/74 (5.4%) 3/104 (2.9%) 2/68 (2.9%) 2/102 (2%)
    Skin redness 9/136 (6.6%) 6/164 (3.7%) 5/114 (4.4%) 4/137 (2.9%) 4/100 (4%) 5/120 (4.2%) 5/91 (5.5%) 2/121 (1.7%) 3/85 (3.5%) 2/119 (1.7%) 4/80 (5%) 2/115 (1.7%) 3/79 (3.8%) 2/113 (1.8%) 6/79 (7.6%) 2/109 (1.8%) 7/74 (9.5%) 5/104 (4.8%) 4/68 (5.9%) 2/102 (2%)
    Chest pain 2/136 (1.5%) 7/164 (4.3%) 7/114 (6.1%) 4/137 (2.9%) 9/100 (9%) 2/120 (1.7%) 4/91 (4.4%) 3/121 (2.5%) 4/85 (4.7%) 7/119 (5.9%) 3/80 (3.8%) 3/115 (2.6%) 3/79 (3.8%) 1/113 (0.9%) 4/79 (5.1%) 2/109 (1.8%) 3/74 (4.1%) 2/104 (1.9%) 1/68 (1.5%) 4/102 (3.9%)
    Weakness on one or both sides of the body 21/136 (15.4%) 23/164 (14%) 18/114 (15.8%) 14/137 (10.2%) 9/100 (9%) 10/120 (8.3%) 7/91 (7.7%) 9/121 (7.4%) 9/85 (10.6%) 15/119 (12.6%) 6/80 (7.5%) 10/115 (8.7%) 7/79 (8.9%) 11/113 (9.7%) 6/79 (7.6%) 13/109 (11.9%) 10/74 (13.5%) 10/104 (9.6%) 5/68 (7.4%) 9/102 (8.8%)
    Psychiatric disorders
    Sleep problems 36/136 (26.5%) 61/164 (37.2%) 23/114 (20.2%) 32/137 (23.4%) 16/100 (16%) 23/120 (19.2%) 20/91 (22%) 13/121 (10.7%) 14/85 (16.5%) 21/119 (17.6%) 17/80 (21.3%) 22/115 (19.1%) 8/79 (10.1%) 14/113 (12.4%) 8/79 (10.1%) 13/109 (11.9%) 7/74 (9.5%) 13/104 (12.5%) 8/68 (11.8%) 10/102 (9.8%)
    Insomnia 21/136 (15.4%) 37/164 (22.6%) 12/114 (10.5%) 20/137 (14.6%) 12/100 (12%) 10/120 (8.3%) 10/91 (11%) 14/121 (11.6%) 12/85 (14.1%) 11/119 (9.2%) 8/80 (10%) 12/115 (10.4%) 7/79 (8.9%) 8/113 (7.1%) 10/79 (12.7%) 5/109 (4.6%) 7/74 (9.5%) 7/104 (6.7%) 8/68 (11.8%) 8/102 (7.8%)
    Abnormal Dreams 8/136 (5.9%) 4/164 (2.4%) 5/114 (4.4%) 8/137 (5.8%) 6/100 (6%) 10/120 (8.3%) 7/91 (7.7%) 7/121 (5.8%) 6/85 (7.1%) 13/119 (10.9%) 5/80 (6.3%) 5/115 (4.3%) 3/79 (3.8%) 7/113 (6.2%) 9/79 (11.4%) 5/109 (4.6%) 5/74 (6.8%) 4/104 (3.8%) 3/68 (4.4%) 3/102 (2.9%)
    Irritability 16/136 (11.8%) 30/164 (18.3%) 11/114 (9.6%) 14/137 (10.2%) 12/100 (12%) 15/120 (12.5%) 8/91 (8.8%) 16/121 (13.2%) 11/85 (12.9%) 10/119 (8.4%) 12/80 (15%) 14/115 (12.2%) 11/79 (13.9%) 10/113 (8.8%) 6/79 (7.6%) 8/109 (7.3%) 7/74 (9.5%) 6/104 (5.8%) 3/68 (4.4%) 7/102 (6.9%)
    Depressed Mood 37/136 (27.2%) 41/164 (25%) 15/114 (13.2%) 21/137 (15.3%) 19/100 (19%) 16/120 (13.3%) 9/91 (9.9%) 14/121 (11.6%) 13/85 (15.3%) 17/119 (14.3%) 8/80 (10%) 16/115 (13.9%) 15/79 (19%) 15/113 (13.3%) 10/79 (12.7%) 6/109 (5.5%) 7/74 (9.5%) 7/104 (6.7%) 9/68 (13.2%) 15/102 (14.7%)
    Anxiety 67/136 (49.3%) 76/164 (46.3%) 57/114 (50%) 55/137 (40.1%) 50/100 (50%) 43/120 (35.8%) 42/91 (46.2%) 42/121 (34.7%) 39/85 (45.9%) 42/119 (35.3%) 41/80 (51.3%) 39/115 (33.9%) 33/79 (41.8%) 31/113 (27.4%) 30/79 (38%) 33/109 (30.3%) 32/74 (43.2%) 27/104 (26%) 25/68 (36.8%) 30/102 (29.4%)
    Agitation 33/136 (24.3%) 44/164 (26.8%) 29/114 (25.4%) 30/137 (21.9%) 31/100 (31%) 34/120 (28.3%) 23/91 (25.3%) 29/121 (24%) 20/85 (23.5%) 28/119 (23.5%) 21/80 (26.3%) 20/115 (17.4%) 24/79 (30.4%) 17/113 (15%) 20/79 (25.3%) 19/109 (17.4%) 21/74 (28.4%) 17/104 (16.3%) 14/68 (20.6%) 20/102 (19.6%)
    Disturbance in attention 13/136 (9.6%) 20/164 (12.2%) 10/114 (8.8%) 8/137 (5.8%) 8/100 (8%) 7/120 (5.8%) 6/91 (6.6%) 7/121 (5.8%) 8/85 (9.4%) 8/119 (6.7%) 5/80 (6.3%) 12/115 (10.4%) 6/79 (7.6%) 10/113 (8.8%) 1/79 (1.3%) 5/109 (4.6%) 7/74 (9.5%) 6/104 (5.8%) 6/68 (8.8%) 3/102 (2.9%)
    Hostility 17/136 (12.5%) 21/164 (12.8%) 14/114 (12.3%) 11/137 (8%) 12/100 (12%) 14/120 (11.7%) 5/91 (5.5%) 12/121 (9.9%) 9/85 (10.6%) 18/119 (15.1%) 8/80 (10%) 13/115 (11.3%) 14/79 (17.7%) 11/113 (9.7%) 10/79 (12.7%) 11/109 (10.1%) 9/74 (12.2%) 9/104 (8.7%) 10/68 (14.7%) 8/102 (7.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Brian Hitsman
    Organization Northwestern University
    Phone 312-504-5834
    Email b-hitsman@northwestern.edu
    Responsible Party:
    Brian Hitsman, Associate Professor of Preventive Medicine, Northwestern University
    ClinicalTrials.gov Identifier:
    NCT02378714
    Other Study ID Numbers:
    • STU00100303
    • 1R01CA184211-01A1
    First Posted:
    Mar 4, 2015
    Last Update Posted:
    Jul 29, 2021
    Last Verified:
    May 1, 2021