Dual Use Cessation for Smoking

Overseen By Mark Zehner

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Wisconsin, Madison

Must be taking: Varenicline, Nicotine patches

Must not be taking: Bupropion

Disqualifiers: Psychosis, Bipolar, Pregnancy, 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

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

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best way to help individuals quit smoking cigarettes and using e-cigarettes. Participants will receive either varenicline (a medication that reduces cravings) or nicotine patches, with different session setups to determine which is more effective. This trial suits those who smoke at least five cigarettes daily, vape weekly for six months, are ready to quit smoking within the next 30 days, and can use a smartphone app. As a Phase 4 trial, the treatment has FDA approval and proven effectiveness, offering participants a chance to benefit from established therapies while contributing to research that aids more patients.

Will I have to stop taking my current medications?

If you are using nicotine replacement, varenicline, or bupropion (only for smoking cessation), you will need to stop taking them to join the trial. If you are taking bupropion for other reasons, like depression, you cannot participate in the trial.

What is the safety track record for these treatments?

A previous study found varenicline safe and effective for adults who smoke. However, it can interact with alcohol, and rare risks exist when using it. Research on nicotine patches has shown they are generally safe, though some people may experience skin irritation. Both treatments can help reduce smoking, but awareness of these possible side effects is important. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the treatments in this trial for smoking cessation because they focus on the use of varenicline and nicotine patches in various combinations and session formats. Varenicline is unique because it targets nicotine receptors in the brain, reducing cravings and withdrawal symptoms, potentially offering a more direct approach than nicotine replacement therapies like patches. What's particularly interesting is the trial's exploration of both dual-focused and smoking-focused sessions, allowing for customized treatment plans that might enhance effectiveness. This could lead to more personalized and flexible options for individuals trying to quit smoking, potentially improving success rates compared to standard treatments.

What evidence suggests that this trial's treatments could be effective for dual users of cigarettes and ENDS?

Research has shown that varenicline, one of the treatments in this trial, effectively helps people quit smoking. In one study, 40% of participants taking varenicline remained smoke-free after 12 weeks, compared to only 8.3% of those not using it. Varenicline reduces cravings and withdrawal symptoms, making quitting easier.

Similarly, the nicotine patch, another treatment option in this trial, has proven effective in helping people quit smoking. Users of the patch are more than twice as likely to quit compared to those not using it. Some studies found that about 39.7% of people could quit smoking with proper use of the nicotine patch.

Both treatments in this trial have been shown to increase the chances of quitting smoking when used correctly. ^{6 7 8 9 10}

Who Is on the Research Team?

Megan E Piper, PhD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for individuals who use both cigarettes and electronic nicotine delivery systems (ENDS) and are looking to quit. Participants will be involved in the study for 12 months.

Inclusion Criteria

Able to read and communicate in English

Smoking ≥ 5 cigarettes per day for the past 6 months

Vaping weekly for at least 6 months

Exclusion Criteria

I am not currently pregnant or breastfeeding.

I am currently taking bupropion for reasons other than to quit smoking.

I am currently receiving treatment for psychosis or bipolar disorder.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either varenicline or nicotine patches for 12 weeks, along with counseling sessions

12 weeks

1-4 counseling sessions

Follow-up

Participants are monitored for smoking and vaping cessation outcomes

52 weeks

Regular follow-up assessments

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine patch
• Varenicline

Trial Overview The study aims to find the best way to help dual users of cigarettes and ENDS quit smoking by comparing different cessation methods: Dual Focused Cessation Counseling, Varenicline with a single session, Nicotine patch, or Smoking Focused Cessation Counseling with four sessions.

How Is the Trial Designed?

Group I: Varenicline, Dual Focused, 1 session Active Control 3 Interventions

Group II: Varenicline, Smoking Focused, 4 sessions Active Control 3 Interventions

Group III: Varenicline, Smoking Focused, 1 session Active Control 3 Interventions

Group IV: Nicotine Patches, Smoking Focused, 4 sessions Active Control 3 Interventions

Group V: Nicotine Patches, Dual Focused, 1 session Active Control 3 Interventions

Group VI: Varenicline, Dual Focused, 4 sessions Active Control 3 Interventions

Group VII: Nicotine Patches, Smoking Focused, 1 session Active Control 3 Interventions

Group VIII: Nicotine Patches, Dual Focused, 4 sessions Active Control 3 Interventions

Varenicline is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Chantix for:

• Smoking cessation
• Dry eye disease

Approved in European Union as Champix for:

• Smoking cessation

Approved in Canada as Champix for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a review of ten randomized controlled trials involving 3091 participants, varenicline did not show a significant increase in overall psychiatric disorders compared to placebo, with an incidence of 10.7% in the varenicline group versus 9.7% in the placebo group.

While varenicline was associated with a higher incidence of sleep disorders, there were no reported cases of suicidal ideation or behavior in the analyzed studies, suggesting that varenicline is generally safe for smokers without current psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. Tonstad, S., Davies, S., Flammer, M., et al.[2022]

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 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]

Varenicline, a medication used to help people quit smoking, is known to have some psychiatric and behavioral side effects, including reports of tardive dyskinesia, although these were not previously documented in literature.

This study presents the first two documented cases of withdrawal emergent dyskinesias associated with varenicline, highlighting a potential safety concern for users of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. Toffey, BA., Rabin, M., Kurlan, R.[2020]

Varenicline is a highly effective medication for smoking cessation, showing superior efficacy compared to placebo and bupropion in clinical trials involving chronic smokers, and it helps alleviate withdrawal symptoms.

The recommended treatment regimen involves starting varenicline one week before the quit date, with a titration schedule to minimize side effects like nausea, making it a suitable option for smokers who struggle with other cessation aids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. Lam, S., Patel, PN.[2017]

In a study of 2,682 patients using varenicline for smoking cessation, nausea and vomiting were the most common reasons for discontinuation and the most frequently reported adverse drug reactions, highlighting the need for patient monitoring regarding gastrointestinal side effects.

While some psychiatric events were reported, including anxiety and depression, all cases of suicidal behavior involved patients with prior psychiatric conditions, suggesting that clinicians should closely monitor individuals with such histories when prescribing varenicline.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and drug utilization profile of varenicline as used in general practice in England: interim results from a prescription-event monitoring study. Kasliwal, R., Wilton, LV., Shakir, SA.[2021]

In a study of 1027 adult smokers, varenicline was found to be significantly more effective for smoking cessation than both placebo and bupropion SR, with 43.9% of participants abstinent during the last 4 weeks of treatment compared to 17.6% and 29.8% respectively.

Varenicline was generally safe and well-tolerated, with the most common side effect being nausea, affecting 29.4% of participants, and a discontinuation rate due to adverse events similar to that of bupropion SR.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. Jorenby, DE., Hays, JT., Rigotti, NA., et al.[2023]

In a study of 12,159 patients, varenicline was associated with reported neuropsychiatric events, particularly anxiety, but no significant increase in these events was found over time, suggesting that the drug's safety profile remains largely stable.

While 7-17% of neuropsychiatric events were attributed to varenicline by general practitioners, the analysis did not raise significant safety concerns, indicating that further investigation is needed to clarify the relationship between varenicline and anxiety symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England. Buggy, Y., Cornelius, V., Fogg, C., et al.[2021]

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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/8201739/

The effectiveness of the nicotine patch for smoking ... Active patch subjects were more than twice as likely to quit smoking as individuals wearing a placebo patch, and this effect was present at both high and low ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0306460397000415

A comparison of measures used to assess effectiveness ... Studies that measured outcome in terms of continuous and prolonged abstinence at 1 year showed double the effect for the active patch compared to placebo; ...

3. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2809121

Adaptive Smoking Cessation Using Precessation ... These studies provided estimates of smoking abstinence rates of 39.7% for adaptive treatment and 23.4% for standard treatment, an absolute ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4410859/

Long-term Nicotine Replacement Therapy However, 6-month rates of smoking cessation rarely exceed 20%. One option that has been explored to enhance the efficacy of the nicotine patch is to extend the ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06474299?aggFilters=phase%3A0+1+2+3+4%2Cstatus%3Anot+rec+act+enr%2CstudyType%3Aint&primComp=2020-01-01_&lastUpdPost=2024-11-08_

NCT06474299 | The Avenues Study: Dual Use Cessation Participants who smoke ≤10 cigarettes per day at baseline will be given 10 weeks of 14 mg nicotine patches followed by 2 weeks of 7 mg patches. Behavioral : ...

6. cdc.gov cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-a-nicotine-patch.html

How to Use Nicotine Patches | Quit Smoking If you smoke more than 10 cigarettes per day, consider starting on the 21 mg patch. Don't wear two patches at once unless directed to do so by your healthcare ...

7. mayoclinic.org mayoclinic.org/drugs-supplements/nicotine-transdermal-route/description/drg-20068808

Nicotine (transdermal route) - Side effects & dosage Nicotine skin patches are used to help you stop smoking. Nicotine is absorbed from the patch on the skin and enters the blood stream.

8. nicorette.com nicorette.com/nicoderm-cq/clear-21mg-14ct/?srsltid=AfmBOoqmmDPiFyBRHBjLvV-8uQ9JjFNgwIaUilwFIEqatHg0hl5MY6IL

Step 1 Nicotine Patches, 21mg (14 Ct) Choose NicoDerm CQ Step 1 patches to help you quit smoking. Choose from three steps to make stopping smoking cigarettes easier.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2917405/

Adverse events associated with nicotine replacement therapy ... Pooled evidence specific to the NRT patch found an increase in skin irritations (OR 2.80, 95% CO, 2.28-3.24, P < 0.001). Orally administered NRT was associated ...

10. camh.ca camh.ca/en/professionals/treating-conditions-and-disorders/smoking-cessation/smoking-cessation---treatment/smoking-cessation---overview-of-nicotine-replacement-therapy

Smoking Cessation: Overview of Nicotine Replacement ... The patch provides a fraction of the nicotine delivered by cigarettes that attenuates the nicotine withdrawal to some extent and allows patients to cut down or ...