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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how electronic cigarettes and the medication varenicline (a smoking cessation aid) can reduce smoking harm for African Americans who currently smoke cigarettes. The study aims to determine if these treatments can help individuals switch fully or partially to e-cigarettes and if varenicline can enhance this effect. Participants will receive either an electronic cigarette, varenicline with an electronic cigarette, or a placebo pill with an electronic cigarette. It is ideal for African Americans who smoke more than five cigarettes a day and are interested in switching to e-cigarettes but not ready to quit smoking completely. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

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.

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

Previous studies on electronic cigarettes (e-cigarettes) have shown mixed safety results. They expose users to harmful substances and can lead to nicotine addiction, including risks of lung diseases. However, for smokers wanting to quit, e-cigarettes might help if used solely to stop smoking regular cigarettes.

Varenicline, a medication that aids smoking cessation, can cause side effects like nausea and headaches. Although there is a small risk of heart-related problems, it helps many people quit smoking more effectively than a placebo.

Both treatments carry risks but also offer potential benefits. They aim to assist those looking to stop smoking. Always consult a healthcare provider to consider these factors. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining electronic cigarettes with varenicline for smoking cessation because this approach offers a novel dual-action strategy. Unlike traditional nicotine replacement therapies that mainly substitute nicotine, this combination not only provides a familiar hand-to-mouth action through e-cigarettes but also uses varenicline to reduce cravings and withdrawal symptoms by acting on brain receptors. This dual method could potentially enhance the effectiveness of quitting smoking by addressing both the physical and behavioral aspects of addiction, making it a promising alternative to standard treatments like nicotine patches or gums.

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

Research has shown that both varenicline and electronic cigarettes (ECs) can help people quit smoking. In this trial, participants will join different treatment arms to evaluate these options. One study found that varenicline doubled the likelihood of quitting compared to a placebo, which contains no active medicine. Another study found that ECs with nicotine can be as effective as varenicline for quitting smoking. For those trying to stop using e-cigarettes, varenicline also showed good results. Overall, both treatments offer effective options for people who want to quit smoking. ^{6 7 8 9 10}

Who Is on the Research Team?

Nicole Nollen, PhD

Principal Investigator

University of Kanas Medical Center

Are You a Good Fit for This Trial?

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

African American

Smoke >5 cigarettes per day

Smoked cigarettes for > 6 months

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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 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 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]

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]

Citations

1. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/2820176

Electronic Cigarettes vs Varenicline for Smoking Cessation ... This randomized clinical trial found that varenicline and nicotine-containing ECs were both effective in helping individuals in quitting smoking conventional ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10825782/

Efficacy of Electronic Cigarettes vs Varenicline and Nicotine ... Validated 7-day point prevalence abstinence rates were affected less, and effect sizes for all outcomes were close to those predicted, but the ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871625003370

Efficacy and safety of varenicline for electronic cigarette ... First meta-analysis on varenicline for e-cigarette cessation. · Varenicline doubled abstinence rates compared to placebo. · Consistent efficacy across multiple ...

4. hollingscancercenter.musc.edu hollingscancercenter.musc.edu/news/archive/2024/05/16/first-us-trial-of-varenicline-for-ecigarette-cessation-shows-positive-results

First US trial of varenicline for e-cigarette cessation shows ... The first U.S. trial of varenicline for e-cigarette cessation shows promising results and warrants larger-scale trials, the researchers say.

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation Outcomes. The primary outcome was continuous abstinence from tobacco smoking at 6 months as measured by participant report of no cigarette ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10826537/

Safety, efficacy and health impact of electronic nicotine ... The goal of this study is to perform an umbrella review of systematic reviews and meta-analyses to assess the safety, efficacy, health implications and ...

7. cdc.gov cdc.gov/tobacco/e-cigarettes/health-effects.html

Health Effects of Vaping | Smoking and Tobacco Use Vaping is not safe, with nicotine being addictive and harmful, especially for youth and pregnant women. E-cigarette aerosol contains cancer- ...

8. tobaccocontrol.bmj.com tobaccocontrol.bmj.com/content/33/3/373

Risk and safety profile of electronic nicotine delivery systems ... We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes ...

9. cdc.gov cdc.gov/tobacco/e-cigarettes/about.html

About E-Cigarettes (Vapes) | Smoking and Tobacco Use E-cigarette aerosol is NOT harmless “water vapor.” It can contain harmful and potentially harmful substances. E-cigarette sales in the United ...

10. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10952413/

Electronic cigarettes and health outcomes: umbrella and ... E‐cigarettes may be beneficial for smokers who use them to completely and promptly quit smoking, but they are not currently approved smoking ...