Smoking Cessation Therapies for Quitting Smoking

Overseen By Jason Robinson, PHD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Opioids, Smoking cessation meds

Disqualifiers: Pregnancy, Schizophrenia, Bipolar, Substance use, 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: 3

2010 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to find the best way for people to quit smoking by personalizing treatments based on individual traits. Participants may receive medications such as varenicline (a prescription medication), nicotine replacement therapies (like patches or gum), and bupropion (an antidepressant), combined with counseling, to help them quit or reduce smoking. The goal is to determine which treatment combinations work best for different individuals, especially those who have previously tried to quit without success. This trial may suit people who smoke at least five cigarettes a day and are interested in quitting or changing their smoking habits. Participants must live in Texas and be able to join online sessions. As a Phase 4 trial, the treatments are already FDA-approved and proven effective, offering participants a chance to benefit from established therapies.

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

The trial requires you to stop using smoking cessation medications like bupropion, nicotine replacement therapy, or varenicline for at least 7 days before joining. Other medications may be evaluated on a case-by-case basis by the study physician.

What is the safety track record for these treatments?

Research has shown that varenicline is usually well-tolerated, though some study participants reported nausea and headaches. About 28% experienced nausea compared to 8.4% who took a placebo. Headaches affected about 15.5% of those taking varenicline. Despite these side effects, varenicline has proven more effective than a placebo in helping people quit smoking.

Nicotine Replacement Therapy (NRT) products, such as patches, lozenges, or gum, are also considered safe. They help manage cravings and withdrawal symptoms during smoking cessation. NRT is widely used and recommended for adults trying to quit smoking.

Bupropion is another safe treatment option for smoking cessation. While effective for many, it carries a small risk of seizures, though this is rare. Research has shown that bupropion is more effective than a placebo in helping people quit smoking.

Overall, these treatments are generally safe but may cause some mild side effects. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these smoking cessation treatments because they explore various combinations and dosing strategies that aren't typically part of standard care. Standard treatments often include individual use of varenicline, nicotine replacement therapy (NRT), or bupropion, but this trial investigates their combined effects. The unique approaches include using higher doses, switching therapies mid-treatment, and combining varenicline and NRT or adding bupropion for a multi-faceted approach. This could potentially enhance effectiveness and offer more personalized options for those struggling to quit smoking.

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

Research has shown that varenicline, one of the treatments in this trial, is a strong aid for quitting smoking. Studies found that 40% of people using varenicline quit smoking by the end of their treatment, compared to just 8.3% who did not use it. People using varenicline also tend to stay smoke-free for longer periods.

Nicotine replacement therapy (NRT), another treatment option in this trial, provides a safer form of nicotine, reducing the urge to smoke. However, only about 20-25% of people using NRT remain smoke-free six months after quitting. Combining NRT with counseling, as done in this trial, can improve the chances of success.

Bupropion is another option included in some trial arms, with a 19% success rate in keeping people smoke-free after six months. It often works better when combined with other treatments like NRT, increasing quit rates by 20%. These treatments offer different ways to help people quit smoking, and this trial will explore their effectiveness in various combinations. ^{1 3 4 6 7}

Who Is on the Research Team?

Jason Robinson

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for Texas residents who smoke at least 5 cigarettes a day, want to quit or change their smoking habits, and can be reached by phone. They must agree to telehealth treatment and not use other nicotine products during the study. Pregnant women, those with serious medical/psychiatric issues, or using certain medications are excluded.

Inclusion Criteria

Have an address and telephone number where they may be reached

Able to follow verbal and written instructions in English and complete all aspects of the study

Be the only participant in their household currently receiving treatment on this protocol

Exclusion Criteria

Current substance use disorder (Drug Abuse Screening Test [DAST] score > 3; Alcohol Use Disorders Identification Test [USAUDIT] score > 24)

You are experiencing very strong feelings of sadness or depression, or have thoughts of hurting yourself.

I have used smoking cessation medications in the last week.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Stage I

Participants receive varenicline or NRT with counseling for 6 weeks. Those who quit smoking continue treatment for an additional 6 weeks.

6-12 weeks

Weekly visits (in-person or virtual)

Treatment Stage II

Participants who do not quit smoking are randomized to different treatment groups for an additional 6 weeks.

6 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 6 months

Follow-up visits at 3 and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Bupropion Hydrochloride Controlled-release
• Nicotine Replacement
• Tobacco Cessation Counseling
• Varenicline

Trial Overview

The PISCES I Trial is testing personalized treatments for quitting smoking in cancer patients. It includes nicotine replacement therapy, counseling, and medications like varenicline and bupropion. The goal is to find out which combination of these methods works best based on individual characteristics.

How Is the Trial Designed?

Group I: Group VII (varenicline and NRT, counseling) Experimental Treatment 4 Interventions

Participants receive varenicline as in Group I and NRT as in Group II for 6 weeks. Participants also receive behavioral smoking cessation counseling.

Group II: Group VI (varenicline or NRT, bupropion, counseling) Experimental Treatment 5 Interventions

Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive bupropion PO daily for 6 weeks and behavioral smoking cessation counseling.

Group III: Group V (higher dose varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants receive a higher dose and continue to receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group IV: Group IV (varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants switch to a different therapy and receive varenicline as in Group I or NRT as in Group II for 6 weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group V: Group III (varenicline or NRT, counseling) Experimental Treatment 4 Interventions

Participants continue to receive varenicline as in Group I or NRT as in Group II for 6 additional weeks depending on which group they were assigned to. Participants also receive behavioral smoking cessation counseling.

Group VI: Group II (NRT, counseling) Experimental Treatment 3 Interventions

Participants receive NRT consisting of a patch, lozenges, or gum daily for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.

Group VII: Group I (varenicline, counseling) Experimental Treatment 3 Interventions

Participants receive varenicline PO daily or BID for 6 weeks in the absence of unacceptable toxicity. Participants who quit smoking continue treatment for 6 additional weeks in the absence of unacceptable toxicity. Participants also receive behavioral smoking cessation counseling.

Bupropion Hydrochloride Controlled-release is already approved in United States, European Union, Canada, Japan, Switzerland for the following indications:

Approved in United States as Wellbutrin for:

• Major depressive disorder
• Seasonal affective disorder
• Smoking cessation

Approved in European Union as Zyban for:

• Smoking cessation

Approved in Canada as Wellbutrin XL for:

• Major depressive disorder
• Seasonal affective disorder

Approved in Japan as Bupropion for:

• Depression

Approved in Switzerland as Wellbutrin SR for:

• Major depressive disorder

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Nicotine replacement therapy (NRT) significantly doubles quit rates for smoking cessation, especially when combined with behavioral therapy, and includes effective options like gum, patches, inhalers, and sprays.

NRT is generally safe for most patients with cardiovascular disease, but its use during pregnancy should be limited to heavy smokers who cannot quit, highlighting the need for careful consideration of patient safety in treatment plans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Nicotine preparations and other preparations for smoking cessation]. Tonstad, S.[2015]

Varenicline (Champix) is a newly approved medication for smoking cessation that acts as a partial agonist of nicotinic receptors, offering a different mechanism of action compared to traditional therapies like nicotine replacement and bupropion.

Recent studies indicate that varenicline is effective in helping individuals quit smoking and may have advantages over existing treatments, although potential side effects are also discussed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Drug of the month. Varenicline (Champix)]. Vandemergel, X.[2015]

In a study involving 294 participants, varenicline was found to be significantly more effective than placebo for smoking cessation, with lasting effects observed up to 6 months after treatment.

Varenicline not only helped with quitting smoking but also reduced symptoms of depression and negative emotions, without increasing the risk of neuropsychiatric adverse events, making it a safe option for those looking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of varenicline and bupropion sustained-release use plus intensive smoking cessation counseling on prolonged abstinence from smoking and on depression, negative affect, and other symptoms of nicotine withdrawal. Cinciripini, PM., Robinson, JD., Karam-Hage, M., et al.[2022]

Combination treatments, particularly varenicline with nicotine patches, can lead to higher smoking abstinence rates compared to using varenicline alone, especially in heavy smokers who are more dependent on tobacco.

Overall, combined medications were well tolerated, making them a viable option for hard-core smokers who have struggled to quit with standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combinations of pharmacological treatments in smoking cessation. A systematic review]. Underner, M., Perriot, J., Peiffer, G., et al.[2021]

In a phase 2 study involving 411 healthy smokers, varenicline tartrate at doses of 1.0 mg once and twice daily significantly increased quit rates compared to placebo, with 48.0% and 37.3% quitting respectively, versus only 17.1% for placebo.

Varenicline was well tolerated, with discontinuation rates due to adverse events similar to placebo, indicating it is a safe and effective option for smoking cessation, especially at the 1.0 mg twice daily dose for long-term success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation with varenicline, a selective alpha4beta2 nicotinic receptor partial agonist: results from a 7-week, randomized, placebo- and bupropion-controlled trial with 1-year follow-up. Nides, M., Oncken, C., Gonzales, D., 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 consensus among 37 international experts led to the development of decision rules for prescribing smoking cessation pharmacotherapy, emphasizing the importance of patient preferences and experiences alongside evidence-based practices.

The guidelines suggest specific combinations of therapies, such as using two forms of nicotine replacement therapy (NRT) or combining bupropion with NRT, particularly for patients with high dependence or those who have not succeeded with monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An algorithm for tailoring pharmacotherapy for smoking cessation: results from a Delphi panel of international experts. Bader, P., McDonald, P., Selby, P.[2023]

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 over 1 million deliveries in Australia, varenicline exposure during pregnancy was associated with a lower risk of adverse perinatal events compared to unexposed women, suggesting it may be a safer option than previously thought.

Varenicline-exposed infants had lower rates of prematurity, being small for gestational age, and severe neonatal complications compared to those exposed to nicotine replacement therapy (NRT), challenging the current preference for NRT over varenicline in pregnant women.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of smoking cessation pharmacotherapies during pregnancy is not associated with increased risk of adverse pregnancy outcomes: a population-based cohort study. Tran, DT., Preen, DB., Einarsdottir, K., et al.[2020]

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 38,954 individuals in the UK, 64.3% of first-time smokers attempting to quit were prescribed nicotine replacement therapy (NRT) patches, with the 21 mg/24 hours patch being the most common option.

The use of combination NRT therapies increased significantly from 25.7% in 2008 to 44.8% in 2011, indicating a trend towards more comprehensive smoking cessation support, but the majority of patients still primarily received patch monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

General practitioner prescribing of single and combination nicotine replacement therapy in the UK: a retrospective database study. Johnson, M., Anderson, P., Lockhart, I.[2021]

In a 52-week study involving 746 participants, varenicline was found to be significantly more effective than transdermal nicotine replacement therapy (NRT) for smoking cessation, with a continuous abstinence rate of 55.9% compared to 43.2% for NRT during the last 4 weeks of treatment.

Varenicline also led to significantly lower levels of craving, withdrawal symptoms, and smoking satisfaction compared to NRT, although it had a higher incidence of nausea as a side effect (37.2% for varenicline vs. 9.7% for NRT).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline versus transdermal nicotine patch for smoking cessation: results from a randomised open-label trial. Aubin, HJ., Bobak, A., Britton, JR., et al.[2022]

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