Smoking Cessation Therapies for Quitting Smoking in People With HIV

(SMARTTT Trial)

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

320 Participants Needed

Trial Summary

What is the purpose of this trial?

Many people living with HIV (PLWH) smoke. Smoking in these individuals is often undertreated. This study plans to assess the ability of various clinical pathways involving tobacco treatment medications and contingency management (paying smokers for not smoking) to improve smoking cessation in a group of PLWH.

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 data supports the effectiveness of the drugs used in smoking cessation therapies for people with HIV?

Research shows that varenicline, bupropion, and nicotine replacement therapy (NRT) are effective for smoking cessation. Varenicline has a drug effect of 2.27, bupropion 1.69, and NRT 1.60 compared to placebo, indicating they help more people quit smoking than a placebo. ^{1 2 3 4 5}

Is smoking cessation treatment safe for people with HIV?

Nicotine replacement therapy, bupropion, and varenicline are considered safe for smoking cessation, with regulatory agencies viewing them as having a favorable benefit/risk profile. However, patients should be monitored for neuropsychiatric symptoms, especially if they have a history of mental health issues. ^{1 5 6 7 8}

How is the drug varenicline unique for helping people with HIV quit smoking?

Varenicline is unique for helping people with HIV quit smoking because it not only aids in smoking cessation but also may improve mood and cognitive function, which are common barriers for this group. Additionally, combining varenicline with text messaging and phone counseling can significantly increase adherence and smoking abstinence rates. ^{9 10 11 12 13}

Research Team

E. Jennifer Edelman, MD, MHS

Principal Investigator

Yale University

Steven Bernstein, MD

Principal Investigator

Dartmouth College

Eligibility Criteria

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

I am 18 years old or older.

You smoke at least five cigarettes a day.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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 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]

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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for smoking cessation: pharmacological principles and clinical practice. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Using extended cognitive behavioral treatment and medication to treat dependent smokers. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic intervention in habitual smoking. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Receipt of Smoking Cessation Medications Among People With and Without Human Immunodeficiency Virus in the Veterans Aging Cohort Study (2003-2018). [2023]

7. Poland pubmed.ncbi.nlm.nih.gov

Which drug to be used in smoking cessation? [2017]

8. England pubmed.ncbi.nlm.nih.gov

Empowering smokers with a web-assisted tobacco intervention to use prescription smoking cessation medications: a feasibility trial. [2019]

9. United States 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. [2022]

10. Netherlands 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. [2018]

11. England pubmed.ncbi.nlm.nih.gov

Motivation and patch treatment for HIV+ smokers: a randomized controlled trial. [2022]

12. Germany pubmed.ncbi.nlm.nih.gov

The effect of varenicline on mood and cognition in smokers with HIV. [2022]

13. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Why are Antidepressant Drugs Effective Smoking Cessation Aids? [2023]