Adaptive Treatment for Smoking Relapse

(ADAPT Trial)

Overseen By Matthew J Carpenter, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medical University of South Carolina

Disqualifiers: Non-smokers

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 12 weeks

544 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a research study to find out if treatment decision making can be improved for smokers who find it difficult to quit with medications. Everyone who participates in this study will receive free product, either nicotine replacement therapies (patches and lozenges), varenicline, or a harm reduction product (e-cigarette) for a full 12 weeks. Most participants will receive some combination of these treatments, depending on individual response to each. All visits and study assessments will be entirely remote. All treatments will be provided free of charge for the first 12 weeks. After that, the study team will contact the participants 6 months after the first study phone call to complete another survey. The study lasts six months and will involve 8 surveys.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

What data supports the effectiveness of the drug Chantix for smoking cessation?

Research shows that Chantix (varenicline) helps people quit smoking by reducing the chance of relapse after a slip during a quit attempt. In one study, switching to Chantix after initial treatment with a nicotine patch increased the likelihood of staying smoke-free at six months. ^{1 2 3 4 5}

Is the treatment for smoking relapse, known as Chantix or varenicline, safe for humans?

Varenicline (Chantix) is generally used for smoking cessation, but there are safety concerns. It may cause neuropsychiatric side effects (mental health-related issues), seizures, and interactions with alcohol. Some people have also reported abnormal sleep-related events. ^{4 6 7 8 9}

How is the drug Chantix (varenicline) unique for treating smoking relapse?

Chantix (varenicline) is unique because it not only helps people quit smoking by reducing withdrawal symptoms and cravings, but it also lowers the chance of a full relapse if someone slips and smokes a cigarette during their quit attempt. This makes it different from other treatments that may not address the risk of relapse as effectively. ^{4 7 10 11 12}

Eligibility Criteria

This trial is for smokers who are eager to quit. It's not suitable for non-smokers or those who aren't looking to stop smoking.

Inclusion Criteria

I am a smoker and want to quit.

Exclusion Criteria

Non-smokers

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a 12-week course of smoking cessation treatment, including nicotine replacement therapies, varenicline, or e-cigarettes, with adaptive adjustments based on response.

12 weeks

All visits and assessments are remote

Follow-up

Participants are monitored for smoking cessation outcomes and other measures at 6 months after the start of the study.

12 weeks

Final follow-up survey at 6 months

Treatment Details

Interventions

• Adaptive Treatment for Early Smoking Cessation Relapse

Trial Overview The study tests if changing treatments helps people struggling to quit smoking. Participants will use nicotine replacement, varenicline, or e-cigarettes and may switch between them based on their quitting progress.

Participant Groups

Group I: Non-Adaptive Randomization 2 Experimental Treatment 1 Intervention

This arm includes people who did not respond to two 4-week courses of pharmacotherapy (either varenicline or combination NRT or both sequentially). After two four-week courses of pharmacotherapy, participants that are not responding to the medication will receive four additional weeks of the same medication with instructions to try to quit again.

Group II: Non-Adaptive Randomization 1 Experimental Treatment 1 Intervention

This arm includes people who did not respond to 4 weeks of pharmacotherapy (either varenicline or combination NRT). After a 4-week course of pharmacotherapy, participants that are not responding to the medication will receive four additional weeks of the same medication with instructions to try to quit again

Group III: Harm Reduction Randomization 2 Experimental Treatment 1 Intervention

This arm includes people who did not respond to two 4-week courses of pharmacotherapy (either varenicline or combination NRT or both). After two 4-week courses of pharmacotherapy, participants who are not responding to medication will be randomly assigned to a harm reduction group (e-cigarettes). Participants assigned to the harm reduction group will receive four weeks of e-cigarette product with instructions to switch completely

Group IV: Adaptive Randomization 1 Experimental Treatment 1 Intervention

This arm includes people who did not respond to 4 weeks of pharmacotherapy (either varenicline or combination NRT). After a 4-week course of pharmacotherapy, participants that are not responding to medication will receive four weeks of the other FDA approved option, either varenicline or combination NRT, with instructions to try to quit again

Adaptive Treatment for Early Smoking Cessation Relapse is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 606 smokers, those who did not significantly reduce their smoking after one week on a nicotine patch benefited from adding bupropion, with abstinence rates increasing from 16% to 28%.

Switching to varenicline also improved outcomes, with 16.5% abstinence at 6 months compared to 6.6% for those who continued with the nicotine patch alone, demonstrating the effectiveness of adaptive treatment strategies in smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapting smoking cessation treatment according to initial response to precessation nicotine patch. Rose, JE., Behm, FM.[2022]

Smokers who achieve abstinence later during a 12-week treatment with varenicline are at a higher risk of relapse, with quit rates significantly declining the longer they take to quit; for example, those who quit in week 11 had only a 5.7% success rate at 52 weeks compared to 54.9% for those who quit in week 1.

Patients who initially struggle to quit benefit more from an extended course of varenicline treatment, suggesting that prolonged support can help those who do not achieve immediate abstinence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment. Hajek, P., Tønnesen, P., Arteaga, C., et al.[2017]

Current FDA-approved medications for smoking cessation are effective for only about one-third of users, highlighting the need for more personalized treatment approaches.

Using biomarkers to tailor tobacco treatment could enhance medication effectiveness, improve patient adherence, and minimize side effects, but challenges remain in translating these biomarkers into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of biomarkers to guide precision treatment for tobacco use. Siegel, SD., Tindle, HA., Bergen, AW., et al.[2023]

In a study of 47 daily smokers, those taking varenicline showed slower relapse rates and higher total abstinence after experiencing a programmed smoking lapse compared to those on a placebo.

Varenicline appears to reduce the perceived reward and effects of smoking, which may help prevent relapse during quit attempts, highlighting its effectiveness as a smoking cessation aid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varenicline on abstinence and smoking reward following a programmed lapse. McClure, EA., Vandrey, RG., Johnson, MW., et al.[2021]

Adaptive pharmacotherapy for smoking cessation, which adjusts treatment based on patient response, led to significantly higher smoking abstinence rates (24%) compared to standard treatment (9%) in a clinical trial with 188 participants.

Participants using varenicline in the adaptive treatment group had a 28% abstinence rate, compared to only 8% in the standard treatment group, indicating that this approach may be particularly effective for those using this medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adaptive Smoking Cessation Using Precessation Varenicline or Nicotine Patch: A Randomized Clinical Trial. Davis, JM., Masclans, L., Rose, JE.[2023]

In a study involving 517 healthy smokers over 12 weeks, varenicline tartrate at doses of 0.5 mg and 1.0 mg twice daily significantly increased smoking cessation rates compared to placebo, with quit rates of 44.0% and 49.4% respectively during weeks 9-12.

Varenicline was generally well tolerated, with nausea reported in 16% to 42% of participants, but titrated dosing resulted in fewer nausea cases and did not often lead to discontinuation of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. Oncken, C., Gonzales, D., Nides, M., et al.[2022]

In a study of 207 cancer patients who smoke, extended use of varenicline (24 weeks) did not significantly improve smoking cessation rates compared to standard use (12 weeks), but adherence to treatment was crucial for success.

Adherent patients using extended varenicline had higher abstinence rates at weeks 24 and 52, indicating that while the treatment duration itself didn't change outcomes for all, it was beneficial for those who consistently followed the regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. Schnoll, R., Leone, F., Veluz-Wilkins, A., et al.[2020]

Smoking cessation is crucial for health, and psychiatric nurses should actively support patients in using therapies like varenicline (Chantix) to quit smoking.

Recent research has raised safety concerns about varenicline, including its potential links to neuropsychiatric side effects, seizures, and interactions with alcohol, which clinicians need to consider when recommending this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. Tobin, TJ., Tobin, ML.[2018]

A review of 27 adverse drug reaction reports linked to varenicline revealed that it can cause 'abnormal sleep related events,' including aggressive behavior during sleep and disturbing dreams, which may resemble sleep disorders.

Most patients experiencing these harmful sleep events showed improvement after stopping varenicline, indicating a potential safety concern that should be addressed in product information and patient guidance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline and abnormal sleep related events. Savage, RL., Zekarias, A., Caduff-Janosa, P.[2018]

Participants who chose varenicline (3,116 individuals) for tobacco cessation had higher abstinence rates at both 3 months (22%) and 6 months (17%) compared to those using nicotine replacement therapy (NRT) (13% at 3 months and 11% at 6 months), indicating that varenicline may be more effective in supporting quitting.

The study found that factors such as increasing age, having health insurance, and the number of counseling sessions were associated with higher rates of abstinence, particularly at 3 months, suggesting that these factors could enhance the effectiveness of quitline services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. Biazzo, LL., Froshaug, DB., Harwell, TS., et al.[2015]

In a randomized controlled trial, varenicline (Chantix) demonstrated a higher abstinence rate from smoking after one year compared to both bupropion SR (Zyban) and a placebo, indicating its efficacy in treating tobacco dependence.

Despite its effectiveness, varenicline has been associated with serious neuropsychiatric side effects, highlighting the importance of discussing potential risks and benefits with patients considering this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of nicotine dependence with Chantix (varenicline). Rankin, KV., Jones, DL.[2015]

In a study of 101 participants, 43% successfully quit smoking after 12 weeks of treatment with varenicline and interactive voice response (IVR) support, but extended IVR did not significantly improve long-term abstinence rates.

At the 2-year mark, only 13% of the original participants remained smoke-free, with no significant difference in relapse rates between those who received extended IVR support and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended interactive voice response telephony (IVR) for relapse prevention after smoking cessation using varenicline and IVR: a pilot study. McNaughton, B., Frohlich, J., Graham, A., et al.[2021]

References

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

Adapting smoking cessation treatment according to initial response to precessation nicotine patch. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Varenicline in prevention of relapse to smoking: effect of quit pattern on response to extended treatment. [2017]

3. Netherlands pubmed.ncbi.nlm.nih.gov

The use of biomarkers to guide precision treatment for tobacco use. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Effects of varenicline on abstinence and smoking reward following a programmed lapse. [2021]

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

Adaptive Smoking Cessation Using Precessation Varenicline or Nicotine Patch: A Randomized Clinical Trial. [2023]

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

Efficacy and safety of the novel selective nicotinic acetylcholine receptor partial agonist, varenicline, for smoking cessation. [2022]

7. England pubmed.ncbi.nlm.nih.gov

A randomized controlled trial of 24 weeks of varenicline for tobacco use among cancer patients: Efficacy, safety, and adherence. [2020]

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

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. [2018]

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

Varenicline and abnormal sleep related events. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. [2015]

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

Treatment of nicotine dependence with Chantix (varenicline). [2015]

12. England pubmed.ncbi.nlm.nih.gov

Extended interactive voice response telephony (IVR) for relapse prevention after smoking cessation using varenicline and IVR: a pilot study. [2021]