Smoking Cessation Therapies for Quitting Smoking in People With HIV

(SMARTTT Trial)

No longer recruiting at 3 trial locations

Overseen By June-Marie Weiss, MA, MEd

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Yale University

Must not be taking: NRT, VAR, Bupropion

Disqualifiers: Pregnancy, Unstable condition, 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: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help people living with HIV quit smoking by testing different combinations of smoking cessation treatments. Participants will try various methods such as nicotine patches, gum, or sprays, sometimes paired with contingency management (receiving payments for not smoking). The study will determine which approach best helps individuals stop smoking. It suits those who have HIV, smoke regularly, and receive care at specific hospitals. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, offering participants the opportunity to benefit from established therapies.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are currently using nicotine replacement therapy, varenicline, or bupropion.

What is the safety track record for these treatments?

Research shows that the treatments used in this study are generally safe. Nicotine replacement therapy (NRT), which includes patches, gums, inhalers, and sprays, is well-researched and commonly used to help people quit smoking. The FDA has approved it, and it helps manage cravings by providing small amounts of nicotine without the harmful effects of smoking.

Contingency management, which uses financial rewards to encourage quitting smoking, has proven effective in many studies. It often supports behavior changes, like quitting smoking, and is considered safe.

Varenicline is another medication often used to help people stop smoking. Research has shown it to be safe, even for people with HIV, although some may experience side effects.

Bupropion is a medication that helps people quit smoking and also treats depression. It is known to be safe for people living with HIV and has been shown to aid in quitting smoking.

Overall, these treatments are well-tolerated, and substantial research backs their safety, especially since the study is in a later phase where safety is well-established. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the combination of smoking cessation therapies for people with HIV because it offers a multi-faceted approach to quitting smoking. Unlike standard nicotine replacement therapies (NRT) like patches or gum, this trial investigates combinations such as NRT with contingency management (CM), which uses positive reinforcement to encourage quitting. Additionally, non-responders have the option to switch to varenicline or bupropion, which are medications that target nicotine cravings differently by affecting brain chemistry. These varied strategies aim to address both the physical and psychological aspects of addiction, offering a personalized and potentially more effective path to quitting smoking for people living with HIV.

What evidence suggests that this trial's treatments could be effective for smoking cessation in people with HIV?

Research has shown that nicotine replacement therapy (NRT), such as patches or sprays, can help people quit smoking, especially when combined with support or counseling. In this trial, some participants will receive NRT alone, while others will receive NRT combined with contingency management, which offers payments as an incentive to quit. Varenicline is another treatment option in this trial. Studies have shown it to be effective for people with HIV, with about 34% quitting by the end of treatment. Bupropion is also under study in this trial and has helped people with HIV quit smoking, achieving nearly 40% success when used with counseling. Overall, these treatments have shown promise in helping people with HIV quit smoking. ^{5 6 7 8 9}

Who Is on the Research Team?

E. Jennifer Edelman, MD, MHS

Principal Investigator

Yale University

Steven Bernstein, MD

Principal Investigator

Dartmouth College

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are HIV positive, smoke cigarettes regularly, and receive care at specific hospitals. They must have smoked more than 100 cigarettes in their lifetime and currently smoke at least 5 a day. Pregnant or nursing individuals, non-cigarette nicotine users, those already on smoking cessation treatments, or with unstable health conditions cannot join.

Inclusion Criteria

Receiving HIV care at Yale-New Haven Hospital, Mount Sinai Hospital, or SUNY Downstate STAR clinic

You smoke at least five cigarettes a day.

Have smoked >= 100 cigarettes in lifetime

Exclusion Criteria

Self-report or urine testing confirming pregnancy, nursing, or trying to conceive

Inability to provide at least one collateral contact (family member or friend)

Using only non-cigarette nicotine products (i.e., e-cigs, Juul, etc.)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage 1

Participants are randomized to either combination nicotine replacement therapy (NRT) or NRT with contingency management (CM) for 12 weeks

12 weeks

Treatment Stage 2

Responders continue with the same treatment for another 12 weeks. Non-responders are re-randomized to either switch medication or intensify CM

12 weeks

Follow-up

Participants are monitored for self-reported reduction in average cigarettes smoked per day and other health outcomes

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion
• Contingency Management
• Nicotine gum
• Nicotine inhaler
• Nicotine nasal spray
• Nicotine patch
• Varenicline

Trial Overview

The study tests different methods to help people living with HIV quit smoking. It includes using nicotine patches, gums, nasal sprays, inhalers and medications like Varenicline or bupropion combined with Contingency Management which rewards participants for not smoking.

How Is the Trial Designed?

Group I: 12 wks NRT/ 12 wks VAR or bupropion Experimental Treatment 2 Interventions

Nicotine replacement therapy alone. Non-responders switch to varenicline or bupropion alone for second 12 weeks.

Group II: 12 wks NRT/ 12 wks NRT+CM Experimental Treatment 2 Interventions

Nicotine replacement therapy alone. Non-responders switch to nicotine replacement therapy combined with contingency management for second 12 weeks.

Group III: 12 wks NRT/ 12 wks NRT Experimental Treatment 1 Intervention

Nicotine replacement therapy alone. Responders remain on nicotine replacement therapy.

Group IV: 12 wks NRT+CM/12 wks NRT+CM plus Experimental Treatment 2 Interventions

Nicotine replacement therapy combined with contingency management Non-responders switch to nicotine replacement therapy combined with intensified contingency management for second 12 weeks.

Group V: 12 wks NRT+CM/ 12 wks VAR or bupropion+CM Experimental Treatment 3 Interventions

Nicotine replacement therapy combined with contingency management. Non-responders switch to varenicline or bupropion combined with contingency management for second 12 weeks.

Group VI: 12 wks NRT+CM / 12 wks NRT+CM Experimental Treatment 2 Interventions

Nicotine replacement therapy combined with contingency management. Responders remain on same treatment for second 12 weeks.

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?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Nicotine replacement therapy (NRT) is recommended as the first-line treatment for smoking cessation due to its well-documented efficacy and mild side effects, with a 1-year quit rate of about 20-25% when combined with counseling.

Varenicline is slightly more effective than bupropion SR for quitting smoking, but both are suitable options for individuals who have not succeeded with NRT, especially considering the potential side effects associated with bupropion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? Tønnesen, P.[2017]

In a study involving 248 people living with HIV, varenicline combined with counseling significantly increased the rate of smoking cessation compared to placebo, with 15% of participants in the varenicline group achieving continuous abstinence from weeks 9 to 48.

The safety profile of varenicline was favorable, showing a lower incidence of depression in the varenicline group (2%) compared to the placebo group (10%), indicating that varenicline is a safe and effective option for smoking cessation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of varenicline for smoking cessation in people living with HIV in France (ANRS 144 Inter-ACTIV): a randomised controlled phase 3 clinical trial. Mercié, P., Arsandaux, J., Katlama, C., et al.[2018]

In a study of 158 people living with HIV, combining varenicline with text message support and adherence-focused behavioral therapy significantly improved smoking abstinence rates compared to standard care alone after 12 weeks.

The research highlights the importance of intensive behavioral support in smoking cessation programs for people living with HIV, suggesting that enhancing adherence self-efficacy can lead to better treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining Text Messaging and Telephone Counseling to Increase Varenicline Adherence and Smoking Abstinence Among Cigarette Smokers Living with HIV: A Randomized Controlled Study. Tseng, TY., Krebs, P., Schoenthaler, A., 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 173 people living with HIV/AIDS, varenicline significantly reduced anxiety levels compared to placebo, which may help improve smoking cessation efforts.

Reductions in anxiety were linked to a higher likelihood of quitting smoking, suggesting that addressing anxiety could be crucial for smokers with HIV who want to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of varenicline on mood and cognition in smokers with HIV. Thompson, M., Schnoll, R., Serrano, K., et al.[2022]

In a study of 11,968 participants in Taiwan, varenicline was found to be more effective than nicotine replacement therapy (NRT) patch in achieving smoking abstinence, with higher odds ratios for 7-day, 1-month, and 6-month point-prevalence rates.

Varenicline showed significant benefits for both women and smokers with light to moderate nicotine dependence, indicating its effectiveness across different demographics and levels of nicotine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. Chang, PY., Lo, PC., Chang, HC., et al.[2018]

A study involving 406 smokers evaluated the effectiveness of extended treatment with sustained-release bupropion and cognitive-behavioral therapy (CBT) over 40 weeks, showing that all extended treatments were more effective than standard treatment.

CBT, when combined with treatment, significantly improved long-term smoking abstinence rates at weeks 64 and 104, suggesting that brief provider contact and CBT can enhance long-term success in quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using extended cognitive behavioral treatment and medication to treat dependent smokers. Hall, SM., Humfleet, GL., Muñoz, RF., et al.[2021]

Citations

1.

evidence.nejm.org

evidence.nejm.org/doi/full/10.1056/EVIDoa2400090

Efficacy of Smoking Cessation Interventions among People ...

Both bupropion and PSF cessation counseling were effective in promoting abstinence from smoking at 36 weeks.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4021585/

Smoking Cessation Interventions in HIV-Infected Adults ...

A small, prospective study in Europe (N=21) reported that bupropion, an antidepressant approved for smoking cessation, was effective in maintaining abstinence ...

3.

uchicagomedicine.org

uchicagomedicine.org/forefront/research-and-discoveries-articles/2025/february/researchers-look-for-the-best-ways-to-help-people-with-hiv-quit-smoking

Researchers look for the best ways to help people with HIV ...

Most impressively, nearly 40% of participants who received both bupropion and Positively Smoke Free successfully quit smoking for the long term.

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8607828/

Effectiveness of a Smoking Cessation Algorithm Integrated ...

A smoking cessation pharmacotherapy recommendation algorithm integrated into HIV primary care may increase treatment utilization and smoking abstinence.

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT02146911

The MATCH (Medication Aids for Tobacco Cessation and ...

The primary objective of this study is to evaluate the real-world long-term effectiveness of of bupropion and varenicline treatment in a community sample of ...

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC2528204/

The use of bupropion SR in cigarette smoking cessation

Bupropion has been shown to be a safe and cost effective smoking cessation agent. Despite this, NRT remains the dominant pharmacotherapy to aid smoking ...

7.

cdc.gov

cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-bupropion-sr.html

How to Use Bupropion SR | Quit Smoking

Bupropion is a pill you take twice a day. You start it 1-2 weeks before quitting. It does not contain nicotine, so it works differently than nicotine ...

8.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5103932/

Smoking Cessation for People Living With HIV/AIDS

Bupropion has demonstrated efficacy and tolerability among PLWHA being treated for depression (eg, ref.). Some have suggested that ritonavir may ...

9.

jamanetwork.com

jamanetwork.com/journals/jamainternalmedicine/fullarticle/216228

Effectiveness of Bupropion Sustained Release for Smoking ...

Even the least intensive treatment evaluated in the present study (150 mg of bupropion SR plus ZAP) resulted in a short-term quit rate of approximately 24%.