Smoking Cessation Cognitive Behavioral Therapy (CBT) for Post-Traumatic Stress Disorder (PTSD)

(CPT-SMART Trial)

Overseen By Angela C Kirby, MS

Age: 18+

Sex: Any

Travel: May Be Covered

Trial Phase: Phase 4

Sponsor: VA Office of Research and Development

Must be taking: Bupropion

Disqualifiers: Myocardial infarction, Psychotic disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if combining different treatments can help Veterans with PTSD (a mental health condition triggered by trauma) quit smoking. It tests a mix of cognitive processing therapy (a type of talk therapy for PTSD), smoking cessation counseling, and a medication called bupropion (an antidepressant that also aids in smoking cessation), alongside a method that rewards quitting smoking. Two groups participate: one receives rewards based on their progress in quitting, while the other receives support without rewards. Veterans who smoke at least ten cigarettes a day, have PTSD, and want to quit smoking while engaging in therapy may be a good fit for this trial. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, aiming to understand how it benefits more patients.

Do I need to stop taking my current medications to join the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, you must be willing to use bupropion (a medication to help quit smoking) and not receive other behavioral smoking counseling or trauma-focused therapy during the study.

What is the safety track record for these treatments?

Research has shown that Cognitive Processing Therapy (CPT) is a proven treatment for PTSD and is generally easy for patients to handle. Studies have combined CPT with treatments like counseling and medication to help people quit smoking, effectively addressing both PTSD and smoking habits.

Bupropion, often used to help people stop smoking, is usually well-tolerated. Some individuals might experience a dry mouth or trouble sleeping, but serious side effects are rare.

Contingency management (CM), used in some parts of the trial, involves rewarding people for not smoking. Other studies have safely used this method to help reduce smoking.

Overall, the treatments in this trial have been tested on people before and are considered safe. Participants might experience some mild side effects, but the treatments are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these treatments for PTSD and smoking cessation because they combine cognitive processing therapy with smoking cessation techniques, using a unique blend of bupropion and intensive behavioral therapies. This approach not only tackles the psychological aspects of PTSD but also integrates cognitive-behavioral strategies specifically designed to help quit smoking. Unlike standard treatments that often handle PTSD and smoking separately, this method combines them, potentially offering a more holistic and effective solution for individuals dealing with both issues simultaneously.

What evidence suggests that this trial's treatments could be effective for PTSD and smoking cessation?

Research has shown that Cognitive Processing Therapy (CPT) effectively treats PTSD by helping individuals process trauma and reduce symptoms. In this trial, participants in the CPT-SMART arm will receive CPT combined with Smoking Abstinence Reinforcement Therapy (SMART), which uses rewards to encourage smoking cessation and has improved quit rates, especially among Veterans with PTSD. Bupropion, a medication included in this treatment arm, also aids in smoking cessation. These combined therapies aim to help individuals with PTSD quit smoking permanently. Participants in the Combined Contact Yoked Control arm will receive a similar intervention but with non-contingent payment to control for compensation and monitoring. ^{1 2 3 4 6}

Who Is on the Research Team?

Eric A Dedert, PhD

Principal Investigator

Durham VA Medical Center, Durham, NC

Are You a Good Fit for This Trial?

Veterans aged 18-80 who smoke at least ten cigarettes daily for the past year, are willing to try quitting and undergo trauma-focused therapy, and currently have PTSD. Participants must speak and write English.

Inclusion Criteria

You are a military veteran.

You have been a smoker for the past year.

I am willing to try quitting smoking and undergo therapy for trauma.

Exclusion Criteria

You currently have posttraumatic stress disorder (PTSD).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Cognitive Processing Therapy combined with Smoking Abstinence Reinforcement Therapy, including cognitive-behavioral counseling, bupropion, and contingency management

8 weeks

Twice weekly monitoring

Follow-up

Participants are monitored for smoking abstinence and treatment engagement

6 months

Follow-up visits at 1-week post-treatment, 4 months, and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion
• Cognitive Processing Therapy
• Smoking Abstinence Reinforcement Therapy
• Smoking Cessation Cognitive Behavioral Therapy (CBT)
• Yoked Contingency Management

Trial Overview The trial is testing CPT-SMART, a combination of Cognitive Processing Therapy (CPT) for PTSD with smoking cessation treatments including behavioral counseling, medication (Bupropion), and Contingency Management that rewards abstinence from smoking.

How Is the Trial Designed?

Group I: CPT-SMART Experimental Treatment 4 Interventions

COGNITIVE PROCESSING THERAPY with SMOKING ABSTINENCE REINFORCEMENT THERAPY (CPT-SMART) - an intervention that combines evidence-based PTSD treatment with guideline-concordant cognitive-behavioral smoking cessation counseling, bupropion, and intensive behavioral therapy through CM.

Group II: Combined Contact Yoked Control Active Control 4 Interventions

COMBINED CONTACT YOKED CONTROL (CCYC) - an intervention that is identical to CPT-SMART for PTSD and smoking treatment, except for using non-contingent payment (i.e., yoked CM) to control for compensation and monitoring.

Bupropion is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in Canada as Zyban for:

• Smoking cessation

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

In a study of 524 smokers, bupropion significantly reduced negative affect and urges to smoke on quit day, suggesting it helps manage emotional challenges during smoking cessation.

Despite not affecting pre-cessation emotional changes, bupropion's ability to lower negative feelings on quit day was linked to a reduced risk of smoking relapse, highlighting its efficacy in supporting individuals trying to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of bupropion and cognitive-behavioral treatment for depression on positive affect, negative affect, and urges to smoke during cessation treatment. Strong, DR., Kahler, CW., Leventhal, AM., et al.[2022]

Varenicline is the most effective first-line pharmacotherapy for smoking cessation, showing a significant effect compared to placebo with an odds ratio of 2.27, followed by bupropion (1.69) and nicotine replacement therapy (1.60).

Despite some safety concerns, regulatory agencies deem bupropion and varenicline to have a favorable benefit/risk profile, but healthcare providers should monitor patients for potential neuropsychiatric symptoms, especially in those with psychiatric comorbidities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. Aubin, HJ., Luquiens, A., Berlin, I.[2022]

In a study of 349 weight-concerned women smokers, those who received cognitive behavioral therapy focused on weight concerns (CONCERNS) combined with bupropion therapy had a significantly higher abstinence rate (34.0%) compared to those receiving standard treatment with bupropion (21%) or CONCERNS with placebo (11.5%) at 6 months.

The combination of CONCERNS and bupropion therapy improved smoking cessation rates without affecting postcessation weight gain or weight concerns, indicating that this approach is effective for helping women smokers who are worried about weight.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion and cognitive behavioral therapy for weight-concerned women smokers. Levine, MD., Perkins, KA., Kalarchian, MA., et al.[2022]

In a study involving 4092 participants with psychiatric disorders, varenicline, bupropion, and nicotine patches were found to be well tolerated and effective for smoking cessation, with no significant increase in neuropsychiatric adverse events compared to placebo.

Varenicline demonstrated superior continuous abstinence rates compared to bupropion, nicotine patches, and placebo, indicating its effectiveness across various psychiatric diagnoses without varying efficacy based on the type of disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric Safety and Efficacy of Varenicline, Bupropion, and Nicotine Patch in Smokers With Psychotic, Anxiety, and Mood Disorders in the EAGLES Trial. Evins, AE., Benowitz, NL., West, R., et al.[2020]

In a study of 222 smokers who did not significantly reduce their smoking with nicotine patches, the combination of varenicline and bupropion led to a higher abstinence rate (39.8%) compared to varenicline plus placebo (25.9%).

The combination treatment was particularly effective for male smokers and those with high nicotine dependence, suggesting it may be a better option for these groups when initial nicotine patch treatment fails.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. Rose, JE., Behm, FM.[2022]

Bupropion is the most effective and safe non-nicotine treatment for tobacco dependence, doubling the success rate of quitting smoking, similar to nicotine replacement therapy.

For heavy smokers, combining bupropion with nicotine replacement therapy is recommended for better results, while other antidepressants like nortriptyline, clonidine, and mecamylamine have limited effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[ABC of smoking cessation. Bupropion and other drugs in non-nicotine therapy]. Roddy, E.[2015]

Bupropion is an effective first-line therapy for smoking cessation, recommended in both US and UK guidelines, although its exact mechanism of action remains unclear, likely involving dopaminergic pathways related to the brain's reward system.

While bupropion is cost-effective for helping people quit smoking, it carries a risk of seizures, necessitating caution when used alongside other medications or in patients with conditions that may lower the seizure threshold.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bupropion: risks and benefits. Ross, S., Williams, D.[2013]

A post-marketing study involving 11,735 patients found that bupropion (Zyban) has a generally safe profile for smoking cessation, with minimal side effects reported, including insomnia, nausea, and dizziness as the most common adverse reactions.

The study indicated no significant increase in all-cause mortality among bupropion users compared to a control group, suggesting that bupropion is a safe option for smoking cessation in the general population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety of bupropion (Zyban) for smoking cessation from experience gained in general practice use in England in 2000. Boshier, A., Wilton, LV., Shakir, SA.[2023]

Varenicline is associated with a significantly higher risk of suicidal and self-injurious behavior, with 90% of reported cases linked to this medication, compared to only 7% for bupropion and 3% for nicotine replacement products.

Due to the substantial safety concerns regarding varenicline, it is deemed unsuitable for first-line treatment in smoking cessation, especially when considering its adverse effects compared to bupropion and nicotine replacement therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suicidal behavior and depression in smoking cessation treatments. Moore, TJ., Furberg, CD., Glenmullen, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9420819/

Design and Methodology of a Randomized Clinical Trial A multidimensional treatment combining cognitive processing therapy (CPT) for PTSD, smoking cessation counseling, pharmacotherapy, and contingency management ( ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1551714422001653

Design and methodology of a randomized clinical trial This study aims to test a novel combination of interventions to improve smoking quit rates and treatment engagement among Veterans with PTSD.

3. trialx.com trialx.com/clinical-trials/listings/242215/cpt-smart-for-treatment-of-ptsd-and-cigarette-smoking/?

CPT-SMART for Treatment of PTSD and Cigarette Smoking The investigators have successfully developed a treatment manual that combines CPT with cognitive-behavioral counseling for smoking cessation.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01901848

Study Details | NCT01901848 | CPT and Smoking Cessation However, ICSC was associated with only modest improvements in PTSD symptoms, with no difference between ICSC and smoking cessation treatment alone, suggesting a ...

5. withpower.com withpower.com/trial/phase-4-stress-disorders-traumatic-10-2019-d006f

Smoking Cessation Cognitive Behavioral Therapy (CBT) for Post ... The high smoking rate and difficulty with achieving abstinence indicate a critical need to develop effective interventions for Veterans who smoke and have PTSD.

6. academic.oup.com academic.oup.com/ntr/article/27/9/1524/8071410

Behavioral Activation for Smoking Cessation in Veterans with ... The goal of this study was to increase abstinence among US military veterans with PTSD by augmenting standard smoking cessation treatment with BA. This study ...