E-cigarettes + Varenicline for Smoking Cessation

Recruiting at 1 trial location

Overseen By Tricia Snow, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Kansas Medical Center

Must be taking: Varenicline

Must not be taking: Smoking cessation drugs

Disqualifiers: Uncontrolled hypertension, Heart event, Pregnancy, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

500 Participants Needed

Trial Summary

What is the purpose of this trial?

The objectives of this application are to 1) compare short- and long-term harm reduction and abuse liability potential of a nicotine salt pod-based electronic cigarettes (EC) in African American (AA) exclusive EC, dual cig-EC, and exclusive cig users, 2) characterize factors that predict who switches fully, partially, or not at all, and 3) examine if harm reduction can be further enhanced by treating dual users with varenicline (VAR) to eliminate cigarette smoking.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have used smoking cessation medications in the month before joining. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug Varenicline combined with e-cigarettes for smoking cessation?

Varenicline has been shown to be an effective aid for smoking cessation, as it helps reduce cravings and withdrawal symptoms, and is generally well tolerated. Additionally, combining nicotine replacement therapies with varenicline has been found to increase smoking cessation rates compared to using varenicline alone. ^{1 2 3 4 5}

Is the combination of e-cigarettes and varenicline safe for smoking cessation?

Varenicline, used for smoking cessation, has been associated with some safety concerns, including neuropsychiatric symptoms like depression and suicidal thoughts, as well as a risk of seizures. However, it has been shown to have an acceptable safety profile in several studies. The safety of combining varenicline with e-cigarettes specifically for smoking cessation needs more research. ^{1 6 7 8 9}

How does the drug combination of e-cigarettes and varenicline differ from other smoking cessation treatments?

This treatment is unique because it combines e-cigarettes, which provide a nicotine replacement, with varenicline, a drug that reduces cravings and withdrawal symptoms by partially activating nicotine receptors in the brain. This dual approach may offer a more comprehensive strategy for quitting smoking compared to using either method alone. ^{2 9 10 11 12}

Research Team

Nicole Nollen, PhD

Principal Investigator

University of Kanas Medical Center

Eligibility Criteria

This trial is for African American smokers over 21 years old who smoke more than 5 cigarettes a day and have been smoking for over 6 months. They must be willing to try varenicline, switch to e-cigarettes, and attend all study visits. People can't join if they're trying to quit smoking, have uncontrolled high blood pressure or recent heart issues, certain medical conditions like kidney problems or seizures, are pregnant/breastfeeding, planning to move away soon, using other tobacco products recently or another household member is in the study.

Inclusion Criteria

I am 21 years old or older.

African American

Smoke >5 cigarettes per day

Exclusion Criteria

Interested in quitting smoking

My blood pressure is not higher than 180/105.

I have not had a heart-related event in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open label electronic cigarette

All participants receive an initial 6-week supply of the study electronic cigarette

6 weeks

Treatment

Dual users receive an additional 12 weeks of the electronic cigarette and are randomized to receive either varenicline or placebo

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

34 weeks

Treatment Details

Interventions

• Electronic cigarette
• Placebo
• Varenicline Tartrate

Trial Overview The trial aims to see if switching from regular cigarettes to nicotine salt pod-based e-cigarettes reduces harm and addiction potential among African American smokers. It also tests whether taking varenicline helps dual users (those who use both cigarettes and e-cigarettes) completely stop smoking traditional cigarettes.

Participant Groups

Group I: Varenicline and electronic cigarette Experimental Treatment 2 Interventions

At the end of the 6-week open label phase, dual users of cigarettes and e-cigarettes will receive 1mg varenicline to take twice daily for 12 weeks. They will also receive an additional 12 weeks of the nicotine salt-based pod system e-cigarette.

Group II: Open label electronic cigarette Experimental Treatment 1 Intervention

All participants will receive an initial 6-week supply of the study electronic cigarette.

Group III: Placebo and electronic cigarette Placebo Group 2 Interventions

At the end of the 6-week open label phase, dual users of cigarettes and e-cigarettes will receive placebo pills to take twice daily for 12 weeks. They will also receive an additional 12 weeks of the nicotine salt-based pod system e-cigarette.

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

Approved in United States as Electronic Cigarette for:

• Smoking cessation aid
• Nicotine replacement therapy

Approved in European Union as E-cigarette for:

• Smoking cessation aid

Approved in Canada as Vaporizer for:

• Nicotine replacement therapy

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

Findings from Research

In a study involving 140 daily electronic cigarette users, varenicline combined with counseling significantly increased the continuous abstinence rate from vaping compared to a placebo, with rates of 40.0% vs 20.0% during weeks 4-12.

The study also found that varenicline maintained higher rates of vaping abstinence at 34.3% compared to 17.2% at weeks 4-24, indicating its potential effectiveness in vaping cessation programs with minimal serious adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline and counseling for vaping cessation: a double-blind, randomized, parallel-group, placebo-controlled trial. Caponnetto, P., Campagna, D., Ahluwalia, JS., et al.[2023]

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]

Repackaging varenicline tartrate tablets into a dose administration aid, like Webster-pak®, is feasible and does not compromise the tablets' physical or chemical stability after 6 weeks of storage in humid conditions.

The study confirmed that the repackaged tablets maintained their drug content within the required range, supporting the idea that using dose administration aids can enhance adherence to smoking cessation medications without affecting their effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addressing varenicline adherence through repackaging in a dose administration aid. Drovandi, AD., Robertson, SG., Malau-Aduli, BS., et al.[2022]

Varenicline is an effective and generally well-tolerated medication for smoking cessation, acting as a partial agonist at nicotinic acetylcholine receptors, although further research is needed on its potential neuropsychiatric side effects.

Pharmacoeconomic analyses indicate that varenicline is a cost-effective treatment for smoking cessation, outperforming other therapies like bupropion and nicotine replacement in terms of cost per quality-adjusted life-year gained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacoeconomic spotlight on varenicline as an aid to smoking cessation. Keating, GM., Lyseng-Williamson, KA.[2021]

This study will evaluate the effectiveness and safety of combining nicotine salt e-cigarettes with cytisine for smoking cessation in 800 daily smokers over a 12-week period, with a primary focus on achieving biochemically verified abstinence at six months.

The trial aims to provide real-world evidence on this combination therapy's impact, which could inform future smoking cessation practices and policies in New Zealand.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial. Walker, N., Calder, A., Barnes, J., et al.[2023]

In a real-world study involving 566 participants across four European countries, varenicline was found to be an effective smoking cessation aid, with a 64.6% quit rate by the end of the 12-week treatment period.

The safety profile of varenicline was acceptable, with the most common side effects being mild to moderate nausea (8.9%) and insomnia (2.9%), and only 3.4% of participants discontinued due to treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. Boudrez, H., Gratziou, C., Messig, M., et al.[2015]

Chantix (varenicline tartrate) was approved by the FDA in May 2006 as a smoking cessation aid for adults aged 18 and older.

The approval indicates that Chantix is considered a safe and effective option to help smokers quit, although the abstract does not provide specific efficacy data or study details.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The FDA approves new drug for smoking cessation. [2015]

A study involving 1342 cases of presumed seizures and 5368 controls found no significant association between varenicline use and an increased risk of seizures, suggesting that the black box warning may be unwarranted.

The odds of experiencing a seizure for patients using varenicline were only slightly higher (1.09 times) compared to those not using it, indicating that varenicline may be safer than previously thought regarding seizure risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The risk of varenicline-induced seizure among those who have attempted to quit smoking using pharmacotherapy. Chopra, DA., Shah, AB., Vadhariya, AH., et al.[2020]

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, an FDA-approved medication for smoking cessation, significantly increases the chances of quitting smoking, with continuous abstinence rates 2.7 to 3.1 times higher than placebo over a 52-week period after 12 weeks of treatment.

In addition to helping smokers quit, varenicline reduces cravings and withdrawal symptoms, making it a valuable option for those looking to stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline: a review of its use as an aid to smoking cessation therapy. Keating, GM., Siddiqui, MA.[2018]

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]

Varenicline, a partial agonist of nicotinic receptors, is the first medication specifically approved for helping adults quit smoking, showing a significant impact on smoking cessation rates since its launch in the UK in 2006.

The drug is marketed as having a unique dual action and a higher quit rate compared to bupropion, along with a favorable safety and tolerability profile, making it a prominent option for those seeking to stop smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline for smoking cessation. [2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Varenicline and counseling for vaping cessation: a double-blind, randomized, parallel-group, placebo-controlled trial. [2023]

2. 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]

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

Addressing varenicline adherence through repackaging in a dose administration aid. [2022]

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

Pharmacoeconomic spotlight on varenicline as an aid to smoking cessation. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Effectiveness of varenicline as an aid to smoking cessation: results of an inter-European observational study. [2015]

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

The FDA approves new drug for smoking cessation. [2015]

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

The risk of varenicline-induced seizure among those who have attempted to quit smoking using pharmacotherapy. [2020]

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

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

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

Varenicline: a review of its use as an aid to smoking cessation therapy. [2018]

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

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

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

Varenicline for smoking cessation. [2015]