Behavioral Activation and Varenicline for Smoking Cessation in Depressed Smokers

NCT ID: NCT02378714

Last Updated: 2021-07-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-07-24
• Study Completion Date: 2020-03-13

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.

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.

Conditions

Nicotine Dependence; Major Depressive Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Standard treatment + placebo varenicline

Standard behavioral smoking cessation treatment plus placebo varenicline

Group Type: PLACEBO_COMPARATOR

Standard treatment

Intervention Type: 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.

BASC + placebo varenicline

Behavioral activation for smoking cessation plus placebo varenicline

Group Type: EXPERIMENTAL

BASC

Intervention Type: 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.

Standard treatment + active varenicline

Standard behavioral smoking cessation treatment plus active varenicline

Group Type: ACTIVE_COMPARATOR

Varenicline

Intervention Type: 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.

Standard treatment

Intervention Type: 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.

BASC + active varenicline

Behavioral activation for smoking cessation plus active varenicline

Group Type: EXPERIMENTAL

Varenicline

Intervention Type: 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.

BASC

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BEHAVIORAL

Other Intervention Names

Chantix; Behavioral activation for smoking cessation; Standard Therapy

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Brian Hitsman

Associate Professor of Preventive Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Brian Hitsman, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 24042367 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18298238 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21049087 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22038468 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19527557 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23072580 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 19323966 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20099950 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37943674 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37934573 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37119868 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37069490 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Related Links

http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021928s012s013lbl.pdf

FDA Product Information for Varenicline

Other Identifiers

1R01CA184211-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STU00100303

Identifier Type: -

Identifier Source: org_study_id