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

Trial Summary

What is the purpose of this trial?

The overarching goal of this research is to determine the most effective approach for helping dual users of cigarettes and electronic nicotine delivery systems (ENDS) quit smoking. 500 participants will be enrolled and can expect to be on study for 12 months.

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 data supports the effectiveness of the drug varenicline for smoking cessation?

Research shows that varenicline, also known as Chantix, is effective in helping people quit smoking by reducing withdrawal symptoms and cravings. It has been found to be more effective than bupropion (another smoking cessation drug) and placebo in several studies, with improved quit rates and reduced chances of relapse. ^{1 2 3 4 5}

Is varenicline safe for humans?

Varenicline, used to help people stop smoking, has been linked to some psychiatric side effects like depression and suicidal thoughts. While it can be effective, it's important to discuss these potential risks with a healthcare provider before starting the treatment. ^{1 6 7 8 9}

What makes the drug varenicline unique for smoking cessation?

Varenicline is unique because it is a partial agonist (a type of drug that activates receptors but not as strongly as a full agonist) at the nicotinic acetylcholine receptor, which helps reduce nicotine withdrawal symptoms and cravings, making it more effective than other treatments like bupropion and nicotine replacement therapy. ^{1 3 4 9 10}

Research Team

Megan E Piper, PhD

Principal Investigator

University of Wisconsin, Madison

Eligibility Criteria

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.

Plans to move out of the area for the next 12 months

Timeline

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

Treatment Details

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.

Participant Groups

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

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

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

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

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

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

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

Group VIII: Nicotine Patches, Smoking 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+

Findings from Research

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 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 (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 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]

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 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]

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 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, 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 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]

References

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

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

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

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

3. Belgium pubmed.ncbi.nlm.nih.gov

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

4. United States 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. [2023]

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

Varenicline: a selective alpha4beta2 nicotinic acetylcholine receptor partial agonist approved for smoking cessation. [2017]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Psychiatric adverse events in randomized, double-blind, placebo-controlled clinical trials of varenicline: a pooled analysis. [2022]

7. New Zealand 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. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Neuropsychiatric events with varenicline: a modified prescription-event monitoring study in general practice in England. [2021]

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

Withdrawal-Emergent Dyskinesias following Varenicline Therapy. [2020]

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

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