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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to improve the selection of treatments for smokers struggling to quit using medications. Participants will receive free nicotine patches or lozenges, varenicline (also known as Chantix), or e-cigarettes for 12 weeks, with treatment tailored to their response. This study suits smokers who have tried to quit but need extra help. All activities occur remotely, ensuring convenience for participants. As an unphased trial, it offers a unique opportunity to explore personalized treatment options flexibly and conveniently.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that varenicline helps people quit smoking and is generally safe. Most people tolerate it well. Common side effects include nausea and sleep disturbances, but these are usually mild.

Nicotine replacement therapies (NRT), such as patches and lozenges, have also been well studied. They are generally safe and help reduce cravings and withdrawal symptoms. Mild side effects might include skin irritation from patches or mouth irritation from lozenges.

E-cigarettes, used here for harm reduction, have mixed safety data. Some research suggests they expose users to harmful chemicals and may increase the risk of respiratory issues. However, they are sometimes used to aid smoking cessation.

Overall, all these treatments have been studied for safety, but e-cigarettes remain less understood compared to varenicline and NRT. Participants should consider this when deciding whether to join the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this trial because it explores new ways to tackle smoking relapse by adapting treatment based on individual responses. Traditional treatments for smoking cessation often involve a set course of pharmacotherapy, like varenicline or nicotine replacement therapy (NRT). This trial, however, introduces a flexible approach where participants who don't initially respond to treatment can switch to another option or try a different strategy, such as using e-cigarettes for harm reduction. This adaptive methodology could lead to more personalized and effective quitting strategies, providing hope for those who struggle to quit with standard methods.

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

Research has shown that varenicline, one of the treatments in this trial, can significantly help people stop smoking. One study found that 44% of participants using varenicline quit smoking after a year, outperforming those on a placebo. Nicotine replacement therapies (NRT), such as patches and lozenges, are also under study in this trial and have proven effective, with some studies indicating long-term success in remaining smoke-free. However, NRT often becomes less effective over time compared to varenicline. For e-cigarettes, part of the harm reduction arm in this trial, results are mixed. Some research suggests they might outperform traditional NRT, while other studies find no additional benefit for quitting smoking. Each treatment offers different options for participants trying to quit smoking in this trial. ^{1 2 3 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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 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]

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]

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]

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]

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]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8078138/

Risk of smoking relapse with the use of electronic cigarettes

The aim of this study was to synthesize the risk of smoking relapse with the use of e-cigarettes by former smokers.

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sciencedirect.com

sciencedirect.com/science/article/pii/S0376871624014455

Examining e-cigarettes as a smoking cessation treatment

The analysis found that in 8 of 11 comparisons, e-cigarettes were more effective, and 3 of 11 comparisons reported no statistically significant ...

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tobaccocontrol.bmj.com

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Effectiveness of e-cigarettes as aids for smoking cessation

On average, using e-cigarettes for cessation in 2017 did not improve successful quitting or prevent relapse.

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jamanetwork.com

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Smoking Relapse Among Individuals Who Switched ...

Switching to any tobacco product including e-cigarettes was associated with an 8.5% increase in relapse to smoking over the next year.

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amjmed.com

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Efficacy and Safety of E-Cigarette Use for Smoking Cessation

Overall, these data suggest e-cigarettes appear to be more efficacious than conventional nicotine replacement or behavioral smoking cessation ...

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We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes ...

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accpjournals.onlinelibrary.wiley.com

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Evidence Regarding E‐Cigarettes as a Harm Reduction ...

As a result, e-cigarettes are viewed by some as a potential harm reduction tool for those interested in quitting smoking TC. However, others are ...