Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

NCT02378714 | Completed Phase 4 Results DMC

• 2 other identifiers: STU001003031R01CA184211-01A1
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 2

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.

Conditions

Nicotine Dependence; Major Depressive Disorder

Keywords

Smoking Cessation; Major Depressive Disorder; Nicotine Dependence; Varenicline; Behavioral Activation Therapy; Cigarette Smoking

Outcome Measures

Primary Outcomes (2)

• Bioverified Point-prevalence Abstinence at 27 Weeks

  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.

  27 weeks (24-weeks post-target quit date)

• Adverse Event and Serious Adverse Event Rates

  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.

  Weeks 1 (1-week before starting medication), 6, and 14 (end of medication)

Secondary Outcomes (4)

• Bioverified Point-prevalence Abstinence at 14 Weeks (End of Treatment)

  14 weeks (11-weeks post-target quit date)

• Prolonged Abstinence

  27 weeks (24 weeks post target quit date)

• Continuous Abstinence

  27 weeks (24 weeks post target quit date)

• Time to 7-day Relapse

  27 weeks (24 weeks post target quit date)

Study Arms (4)

Standard treatment + placebo varenicline

PLACEBO COMPARATOR

Standard behavioral smoking cessation treatment plus placebo varenicline

Behavioral: Standard treatment

BASC + placebo varenicline

EXPERIMENTAL

Behavioral activation for smoking cessation plus placebo varenicline

Behavioral: BASC

Standard treatment + active varenicline

ACTIVE COMPARATOR

Standard behavioral smoking cessation treatment plus active varenicline

Drug: Varenicline; Behavioral: Standard treatment

BASC + active varenicline

EXPERIMENTAL

Behavioral activation for smoking cessation plus active varenicline

Drug: Varenicline; Behavioral: BASC

Interventions

Varenicline DRUG

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.

Also known as: Chantix

BASC + active varenicline; Standard treatment + active varenicline

BASC BEHAVIORAL

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.

Also known as: Behavioral activation for smoking cessation

BASC + active varenicline; BASC + placebo varenicline

Standard treatment BEHAVIORAL

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.

Also known as: Standard Therapy

Standard treatment + active varenicline; Standard treatment + placebo varenicline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• adult (18 years of age or older) daily cigarette smokers (1+ cigarettes per day)
• meet criteria for current or lifetime MDD without psychotic features
• 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
• speak, read, and write fluently in English
• able to provide written informed consent
• intend to reside in the geographic area for \>8 months
• 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.
• The candidate had to answer "yes" to the question: "Are you interested in quitting smoking?"

You may not qualify if:

• current enrollment or plan to enroll in another smoking cessation program in the next 8 months
• regular (daily) use of e-cigarettes, chewing tobacco, snuff, snus, or other tobacco products
• current use or plan to use nicotine replacement therapy or other smoking cessation medication within the next 8 months
• medications indicated for bipolar or psychotic disorder if prescribed for bipolar or psychotic disorder
• pregnant or planning to become pregnant within the next 8 months, or breast feeding
• history of seizures or current seizure disorder without medication
• 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
• any prior solid organ transplant or prior hematopoietic stem cell transplant
• alcohol consumption exceeding 28 drinks per week
• cirrhosis or end-stage liver disease
• systolic blood pressure \>185 mmHg or diastolic blood pressure \>110 mmHg after two readings or symptomatic uncontrolled stage II hypertension
• unstable cardiovascular disease within 3 months prior to baseline or other cardiovascular disease requiring hospitalization
• prior hospitalization for heart failure
• previous allergic reaction to varenicline
• high suicide risk based on the Columbia Suicide Severity Rating Scale

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (12)

• Anthenelli RM, Morris C, Ramey TS, Dubrava SJ, Tsilkos K, Russ C, Yunis C. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial. Ann Intern Med. 2013 Sep 17;159(6):390-400. doi: 10.7326/0003-4819-159-6-201309170-00005.

  PMID: 24042367 BACKGROUND

• Blalock JA, Robinson JD, Wetter DW, Schreindorfer LS, Cinciripini PM. Nicotine withdrawal in smokers with current depressive disorders undergoing intensive smoking cessation treatment. Psychol Addict Behav. 2008 Mar;22(1):122-8. doi: 10.1037/0893-164X.22.1.122.

  PMID: 18298238 BACKGROUND

• Ebbert JO, Wyatt KD, Hays JT, Klee EW, Hurt RD. Varenicline for smoking cessation: efficacy, safety, and treatment recommendations. Patient Prefer Adherence. 2010 Oct 5;4:355-62. doi: 10.2147/ppa.s10620.

  PMID: 21049087 BACKGROUND

• Gierisch JM, Bastian LA, Calhoun PS, McDuffie JR, Williams JW Jr. Smoking cessation interventions for patients with depression: a systematic review and meta-analysis. J Gen Intern Med. 2012 Mar;27(3):351-60. doi: 10.1007/s11606-011-1915-2. Epub 2011 Oct 26.

  PMID: 22038468 BACKGROUND

• Hitsman B, Moss TG, Montoya ID, George TP. Treatment of tobacco dependence in mental health and addictive disorders. Can J Psychiatry. 2009 Jun;54(6):368-78. doi: 10.1177/070674370905400604.

  PMID: 19527557 BACKGROUND

• Hitsman B, Papandonatos GD, McChargue DE, DeMott A, Herrera MJ, Spring B, Borrelli B, Niaura R. Past major depression and smoking cessation outcome: a systematic review and meta-analysis update. Addiction. 2013 Feb;108(2):294-306. doi: 10.1111/add.12009.

  PMID: 23072580 BACKGROUND

• Philip NS, Carpenter LL, Tyrka AR, Whiteley LB, Price LH. Varenicline augmentation in depressed smokers: an 8-week, open-label study. J Clin Psychiatry. 2009 Jul;70(7):1026-31. doi: 10.4088/jcp.08m04441. Epub 2009 Mar 24.

  PMID: 19323966 BACKGROUND

• MacPherson L, Tull MT, Matusiewicz AK, Rodman S, Strong DR, Kahler CW, Hopko DR, Zvolensky MJ, Brown RA, Lejuez CW. Randomized controlled trial of behavioral activation smoking cessation treatment for smokers with elevated depressive symptoms. J Consult Clin Psychol. 2010 Feb;78(1):55-61. doi: 10.1037/a0017939.

  PMID: 20099950 BACKGROUND

• Gollan JK, Liverant G, Jao NC, Lord KA, Whitton AE, Hogarth L, Fox E, Bauer AM, Quinn MH, Pizzagalli DA, Leone FT, Papandonatos GD, Schnoll RA, Hitsman B. Depression Severity Moderates Reward Learning Among Smokers With Current or Past Major Depressive Disorder in a Smoking Cessation Randomized Clinical Trial. Nicotine Tob Res. 2024 Apr 22;26(5):639-644. doi: 10.1093/ntr/ntad221.

  PMID: 37943674 DERIVED

• Schnoll R, Wileyto EP, Bauer AM, Fox EN, Blumenthal D, Hosie Quinn M, Leone F, Huffman MD, Khan SS, Gollan JK, Papandonatos GD, Hitsman B. Seeing Through the Blind: Belief About Treatment Randomization and Smoking Cessation Outcome Among People With Current or Past Major Depressive Disorder Who Smoke in a Placebo-Controlled Trial of Varenicline. Nicotine Tob Res. 2024 Apr 22;26(5):597-603. doi: 10.1093/ntr/ntad218.

  PMID: 37934573 DERIVED

• Carroll AJ, Huffman MD, Wileyto EP, Khan SS, Fox E, Smith JD, Bauer AM, Leone FT, Schnoll RA, Hitsman B. Change in cardiovascular health among adults with current or past major depressive disorder enrolled in intensive smoking cessation treatment. J Affect Disord. 2023 Jul 15;333:527-534. doi: 10.1016/j.jad.2023.04.089. Epub 2023 Apr 28.

  PMID: 37119868 DERIVED

• Hitsman B, Papandonatos GD, Gollan JK, Huffman MD, Niaura R, Mohr DC, Veluz-Wilkins AK, Lubitz SF, Hole A, Leone FT, Khan SS, Fox EN, Bauer AM, Wileyto EP, Bastian J, Schnoll RA. Efficacy and safety of combination behavioral activation for smoking cessation and varenicline for treating tobacco dependence among individuals with current or past major depressive disorder: A 2 x 2 factorial, randomized, placebo-controlled trial. Addiction. 2023 Sep;118(9):1710-1725. doi: 10.1111/add.16209. Epub 2023 May 3.

  PMID: 37069490 DERIVED

Related Links

• FDA Product Information for Varenicline

MeSH Terms

Conditions

Tobacco Use Disorder; Depressive Disorder, Major; Smoking Cessation; Cigarette Smoking

Interventions

Varenicline; Standard of Care

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Depressive Disorder; Mood Disorders; Health Behavior; Behavior; Tobacco Smoking; Smoking; Tobacco Use

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Quinoxalines; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Results Point of Contact

• Title: Dr. Brian Hitsman
• Organization: Northwestern University

b-hitsman@northwestern.edu

312-504-5834

Study Officials

• Brian Hitsman, Ph.D.

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Preventive Medicine

Study Record Dates

• First Submitted: February 27, 2015
• First Posted: March 4, 2015
• Study Start: July 24, 2015
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: July 29, 2021
• Results First Posted: May 27, 2021

Record last verified: 2021-05

Locations

US (2)