Quitting Strategies + Varenicline for Smoking Cessation

Recruiting in Palo Alto (17 mi)

Overseen by Lisa Fucito, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Yale University

Must be taking: Varenicline

Must not be taking: Smoking cessation drugs

Disqualifiers: Pregnancy, Severe renal impairment, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to understand whether concurrent treatment for cigarettes and e-cigarettes in which an individual quits both products at the same time (QUIT-C) or sequential treatment in which an individual quits cigarettes first followed by e-cigarettes is more effective for quitting both products. The study will also compare the effect of treatment on health-related biomarkers. All participants will receive varenicline, a medication used to treat tobacco use dependence, counseling, and cessation resources (i.e., links to text-based support, self-change booklet). Varenicline helps to reduce cravings for tobacco use and decreases the pleasurable effects of cigarettes and other tobacco products.

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 cannot participate if you are using any smoking cessation services or FDA-approved smoking cessation medications.

What data supports the effectiveness of this treatment for smoking cessation?

Research shows that combining varenicline (a medication to help quit smoking) with counseling can significantly improve quit rates. In one study, at least 44% of patients successfully quit smoking after 12 weeks of varenicline treatment, and other studies found that adding counseling to varenicline further increased the chances of quitting. ^{1 2 3 4 5}

Is varenicline safe for smoking cessation?

Varenicline, also known as Chantix, has been linked to some safety concerns, including possible neuropsychiatric side effects (mental health-related issues), seizures, and interactions with alcohol. There are also reports of adverse cardiovascular events (heart-related issues) associated with its use. It's important to discuss these risks with a healthcare provider before starting treatment. ^{6 7 8 9 10}

How is the drug varenicline unique for smoking cessation?

Varenicline is unique because it works by partially activating the same receptors in the brain that nicotine does, which helps reduce withdrawal symptoms and cravings while also making smoking less satisfying. This mechanism is different from other treatments like nicotine replacement therapy or bupropion, and it has been shown to be more effective in helping people quit smoking. ^{1 3 7 11 12}

Research Team

Lisa Fucito, PhD

Principal Investigator

Yale University

Eligibility Criteria

This trial is for adults who have been smoking cigarettes and using e-cigarettes for at least 3 months, smoke 5+ cigarettes daily, use e-cigarettes on most days, and are ready to quit both within a month. It's not for pregnant or breastfeeding women, those unable to consent, people with severe kidney issues or unstable heart conditions, or users of other tobacco products more than once a week.

Inclusion Criteria

I am ready to quit smoking and using tobacco products within a month.

Smoke 5 or more cigarettes per day

English literate

Exclusion Criteria

Vulnerable Populations: Pregnant women, children, prisoners, or institutionalized individuals

I am unable to give my own consent for medical procedures.

Individuals using other tobacco or nicotine products besides cigarettes and e-cigarettes > once per week in the last 30 days

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Initial online screening and tele-video/phone call final screening

Treatment

Participants receive 12 weeks of varenicline, weekly individual counseling, and access to cessation resources for either concurrent or sequential cessation of cigarettes and e-cigarettes

12 weeks

Weekly individual counseling sessions

Follow-up

Participants are monitored for cigarette and e-cigarette abstinence and health-related biomarkers

4 weeks

Treatment Details

Interventions

• Counseling (Behavioral Intervention)
• Guided Self-Change Booklets (Behavioral Intervention)
• Varenicline (Anti-smoking Medication)

Trial Overview The study tests if quitting cigarettes and e-cigarettes together (QUIT-C) works better than stopping them one after the other. Participants will all receive Varenicline—a medication that reduces cravings and enjoyment from tobacco—alongside counseling and self-help resources.

Participant Groups

Group I: QUIT-S (Sequential) Experimental Treatment 3 Interventions

Treatment in this arm will focus on cessation of cigarettes followed sequentially by cessation of e-cigarettes. All participants will receive 12-weeks of varenicline, weekly individual counseling, and access to cessation resources including a guided self-change booklet and links to free text-based support. Counseling and cessation resources will emphasize sequential cessation.

Group II: QUIT-C (Concurrent) Experimental Treatment 3 Interventions

Treatment in this arm will emphasize concurrent cessation of cigarettes and e-cigarettes. All participants will receive 12-weeks of varenicline, weekly individual counseling, and access to cessation resources including a guided self-change booklet and links to free text-based support. Counseling and cessation resources will emphasize concurrent cessation.

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 139 long-term nicotine replacement therapy users, varenicline combined with counseling significantly improved the quit rate at 12 weeks (64.3% for varenicline vs. 40.6% for placebo), indicating its efficacy in helping users stop NRT.

Participants taking varenicline experienced lower withdrawal symptoms compared to those on placebo, suggesting that varenicline not only aids in quitting but also makes the process more comfortable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. Tønnesen, P., Mikkelsen, K.[2015]

Participants who chose varenicline (3,116 individuals) for tobacco cessation had higher abstinence rates at both 3 months (22%) and 6 months (17%) compared to those using nicotine replacement therapy (NRT) (13% at 3 months and 11% at 6 months), indicating that varenicline may be more effective in supporting quitting.

The study found that factors such as increasing age, having health insurance, and the number of counseling sessions were associated with higher rates of abstinence, particularly at 3 months, suggesting that these factors could enhance the effectiveness of quitline services.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. Biazzo, LL., Froshaug, DB., Harwell, TS., et al.[2015]

In a study involving 392 adult patients admitted for smoking-related illnesses, those who received varenicline tartrate along with Quitline-counselling had a significantly higher rate of continuous smoking abstinence (31.1%) compared to those who received counselling alone (21.4%).

The results suggest that initiating varenicline treatment in the inpatient setting, combined with counselling, is an effective strategy for promoting long-term smoking cessation, with benefits observed at a 12-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking Termination Opportunity for inPatients (STOP): superiority of a course of varenicline tartrate plus counselling over counselling alone for smoking cessation: a 12-month randomised controlled trial for inpatients. Smith, BJ., Carson, KV., Brinn, MP., et al.[2015]

In a study of 50 veterans using varenicline for smoking cessation, only 30% successfully quit smoking, which is lower than the 44% success rate reported in premarketing studies.

The study found a significant association between underlying psychiatric disorders and treatment failure, with all patients who discontinued due to adverse drug events related to mood changes having a history of mental illness, highlighting the need for careful monitoring in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. Purvis, TL., Mambourg, SE., Balvanz, TM., et al.[2015]

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 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]

A systematic review of 14 randomized controlled trials involving 8216 participants found that varenicline, a smoking cessation drug, is associated with a significantly increased risk of serious cardiovascular events compared to placebo, with an odds ratio of 1.72.

The analysis indicates safety concerns regarding varenicline, as serious cardiovascular events occurred in 1.06% of users compared to 0.82% in the placebo group, suggesting that while varenicline is effective for smoking cessation, it may pose risks to heart health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. Singh, S., Loke, YK., Spangler, JG., et al.[2022]

In a study involving 392 adult patients with smoking-related illnesses, varenicline tartrate (VT) combined with quitline counseling was found to be well tolerated, with nausea being the most common side effect reported in 16.3% of the VT group.

VT demonstrated safety in the inpatient setting, with no significant increase in mortality compared to quitline counseling alone, suggesting it could be integrated into standard care for hospitalized smokers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of varenicline tartrate and counseling versus counseling alone for smoking cessation: a randomized controlled trial for inpatients (STOP study). Carson, KV., Smith, BJ., Brinn, MP., et al.[2018]

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 101 participants, 43% successfully quit smoking after 12 weeks of treatment with varenicline and interactive voice response (IVR) support, but extended IVR did not significantly improve long-term abstinence rates.

At the 2-year mark, only 13% of the original participants remained smoke-free, with no significant difference in relapse rates between those who received extended IVR support and those who did not.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extended interactive voice response telephony (IVR) for relapse prevention after smoking cessation using varenicline and IVR: a pilot study. McNaughton, B., Frohlich, J., Graham, A., et al.[2021]

References

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

Varenicline to stop long-term nicotine replacement use: a double-blind, randomized, placebo-controlled trial. [2015]

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

Smoking quit rates among patients receiving pharmacotherapy who received general practitioner counselling versus intensive counselling: a retrospective cohort study. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Characteristics and abstinence outcomes among tobacco quitline enrollees using varenicline or nicotine replacement therapy. [2015]

4. England pubmed.ncbi.nlm.nih.gov

Smoking Termination Opportunity for inPatients (STOP): superiority of a course of varenicline tartrate plus counselling over counselling alone for smoking cessation: a 12-month randomised controlled trial for inpatients. [2015]

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

Safety and effectiveness of varenicline in a veteran population with a high prevalence of mental illness. [2015]

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

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

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

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

8. England pubmed.ncbi.nlm.nih.gov

Clinical Psychopharmacology Update: Additional Safety Concerns for Using Varenicline (Chantix) for Smoking Cessation Treatment. [2018]

9. Canada pubmed.ncbi.nlm.nih.gov

Risk of serious adverse cardiovascular events associated with varenicline: a systematic review and meta-analysis. [2022]

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

Safety of varenicline tartrate and counseling versus counseling alone for smoking cessation: a randomized controlled trial for inpatients (STOP study). [2018]

11. 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]

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

Extended interactive voice response telephony (IVR) for relapse prevention after smoking cessation using varenicline and IVR: a pilot study. [2021]