Smoking/Vaping Cessation Strategies for Nicotine Withdrawal

(VASP Trial)

Overseen By Larry Hawk, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: State University of New York at Buffalo

Must not be taking: Smoking cessation, Antipsychotics

Disqualifiers: Severe substance dependence, Schizophrenia, Bipolar, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 2

370 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed research, which will systematically and comprehensively characterize the withdrawal among daily vapers compared to daily smokers of combustible cigarettes, filling critical gaps in the understanding of electronic nicotine delivery systems (ENDS) dependence/abuse liability and contributing to the development of therapies for tobacco/nicotine use, the leading preventable cause of death in the US.

Will I have to stop taking my current medications?

The trial requires that you do not use any smoking cessation medication and excludes those on antipsychotic medications. Other medications are not specifically mentioned, so it's best to discuss your current medications with the trial team.

What data supports the effectiveness of the treatment for nicotine withdrawal?

Research suggests that combining different forms of nicotine replacement therapy (NRT), like patches and other methods, may improve the chances of quitting smoking by providing a more tailored approach to managing nicotine cravings. ^{1 2 3 4 5}

Is nicotine replacement therapy (NRT) safe for humans?

Nicotine replacement therapy (NRT) is generally considered safe for humans and is widely used to help people quit smoking. However, some adverse effects have been reported, and safety data specifically for quitline users is limited. ^{5 6 7 8 9}

How does this treatment for nicotine withdrawal differ from others?

This treatment is unique because it focuses on specific strategies for managing nicotine withdrawal symptoms, potentially involving novel combinations or dosages of nicotine replacement therapies (NRTs) that are not standard. Unlike traditional NRTs, which are often used alone, this approach may combine different forms or higher doses to better address cravings and withdrawal symptoms. ^{10 11 12 13 14}

Research Team

Larry Hawk, PhD

Principal Investigator

University at Buffalo

Eligibility Criteria

This trial is for daily vapers or smokers with a nicotine level of 200+ ng/mL, who've been using these products for over 6 months. It's not open to those who use other tobacco products frequently, have high alcohol use scores, severe substance dependencies (excluding tobacco/nicotine), are on smoking cessation or antipsychotic meds, have major depression/suicide risk, or are pregnant.

Inclusion Criteria

I have been vaping or smoking daily for over 6 months.

200+ ng/mL cotinine on a commercially-available quick screen

Exclusion Criteria

I am currently on antipsychotic medication or have a history of schizophrenia or bipolar disorder.

Pregnancy (intake urine screen)

I plan to quit vaping or smoking soon.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lab Visits

Participants complete two 4-hour lab visits, including ad lib use and abstinent visits

1 week

2 visits (in-person)

Assessment

Multi-measure, multi-method assessments of withdrawal facets such as negative affect, craving, and difficulty concentrating

1 week

Follow-up

Participants are monitored for safety and effectiveness after the main assessments

4 weeks

Treatment Details

Interventions

• Acute (24-hour) abstinence
• Ad libitum smoking/vaping

Trial Overview The study aims to understand withdrawal in daily users of vaping devices compared to cigarette smokers by having them either abstain from nicotine for 24 hours or continue usage as desired. This research will help develop treatments for nicotine dependence.

Participant Groups

Group I: Daily Users of ENDS Experimental Treatment 2 Interventions

Participants who use nicotine-containing ENDS daily or near-daily but who do NOT smoke combustible cigarettes daily or near-daily.

Group II: Daily Users of Combustible Cigarettes Experimental Treatment 2 Interventions

Participants who smoke combustible cigarettes daily or near-daily but do NOT use nicotine-containing ENDS daily or near-daily.

Group III: Daily Dual Users of ENDS and Combustible Cigarettes Experimental Treatment 2 Interventions

Participants who both use nicotine-containing ENDS and combustible cigarettes daily or near-daily

Who Is Running the Clinical Trial?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Roswell Park Cancer Institute

Collaborator

Trials

427

Recruited

40,500+

Findings from Research

In a study involving 27 smokers testing various nicotine replacement therapy (NRT) combinations over 5 days, double-patch systems were rated highest for ease of use, safety, and suitability for public use.

However, when it came to effectiveness in helping to quit smoking and managing stress, 70% of participants preferred acute-patch combinations, indicating that combining NRTs could enhance their overall efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preferences among four combination nicotine treatments. Schneider, NG., Koury, MA., Cortner, C., et al.[2018]

Participants receiving an 8-week nicotine replacement therapy (NRT) had significantly higher quit rates (42.5%) compared to those receiving a 4-week NRT (33.3%), indicating that longer NRT duration enhances cessation success.

Among participants in a multiple-call program, those who received both 4-week NRT shipments had a quit rate of 51.1%, compared to 31.1% for those who only received one shipment, suggesting that consistent support and extended NRT can improve outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of a Temporary NRT Enhancement in a State Quitline and Web-Based Program. Cole, S., Suter, C., Nash, C., et al.[2019]

Smokers using nicotine replacement therapy (NRT) for smoking reduction or temporary abstinence reported employing various strategies to reduce cigarette consumption, such as increasing intervals between cigarettes and modifying their smoking techniques.

Nicotine patches were favored for their convenience and prolonged effect, but many smokers lacked awareness of the regulatory restrictions surrounding NRT use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of nicotine replacement therapy for smoking reduction and temporary abstinence: an interview study. Beard, E., Vangeli, E., Michie, S., et al.[2022]

In a study of 737 smokers, varenicline (VR) was found to be more effective than standard nicotine replacement therapy (NRT) in achieving smoking abstinence, particularly in the medium term, with higher continuous abstinence rates at weeks 5-22 and 52.

Both varenicline and extended use of combined nicotine replacement therapy (NRT+) showed significant improvements in early quitting success compared to NRT alone, although long-term quit rates did not differ significantly between these treatments and NRT monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial. Tulloch, HE., Pipe, AL., Els, C., et al.[2018]

In a study involving 504 smokers, the nicotine patch was found to be the least unpleasant option among various nicotine replacement therapies (NRT), suggesting it may have a lower abuse liability compared to gum, spray, and inhaler.

At the 15-week mark, users of the nicotine patch reported no feelings of dependence, while continued use of NRT was linked to the rate of nicotine delivery, with the patch delivering the lowest amount of nicotine compared to other forms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. West, R., Hajek, P., Foulds, J., et al.[2022]

High-dose transdermal nicotine-replacement therapy (NRT) at doses of 42 mg or more daily appears to be safe, with most trials reporting no serious adverse events, although a dose-response relationship for adverse events was noted.

While high-dose NRT showed a numerically higher abstinence rate in most trials, none achieved statistically significant differences in final abstinence rates, indicating that more extensive studies are needed to confirm its efficacy and identify suitable patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose transdermal nicotine replacement for tobacco cessation. Brokowski, L., Chen, J., Tanner, S.[2019]

In a study of 33,690 smokers using nicotine replacement therapy (NRT) through the New York State Smokers' Quitline, about 25% reported adverse effects at 2 weeks, which increased to 42% at 3 months, but most effects were mild.

Only a small percentage (4.4%-5.4%) discontinued NRT due to these adverse effects, indicating that NRT is generally safe for users when proper screening is conducted.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse effects with use of nicotine replacement therapy among quitline clients. Ossip, DJ., Abrams, SM., Mahoney, MC., et al.[2015]

The paper advocates for broader access to nicotine replacement therapy (NRT), suggesting that minors, pregnant smokers, and those with cardiovascular disease should be allowed to use NRT to help reduce dependence on more harmful tobacco products.

It also recommends that NRT should be available for smoking reduction and long-term use, and that regulators should promote the development of safer nicotine delivery devices to compete with cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regulation of nicotine replacement therapies (NRT): a critique of current practice. McNeill, A., Foulds, J., Bates, C.[2016]

A study involving 896 participants from 32 alcohol and other drug (AOD) treatment services found that providing free nicotine replacement therapy (NRT) and training significantly increased NRT use among clients, with 57% using it at 8 weeks and 33% at 6.5 months.

Factors such as being in the treatment group, having higher nicotine dependence, and being motivated to quit were strong predictors of NRT use, particularly in the short term, highlighting the effectiveness of structured support in enhancing smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patterns and predictors of nicotine replacement therapy use among alcohol and other drug clients enrolled in a smoking cessation randomised controlled trial. Guillaumier, A., Skelton, E., Tzelepis, F., et al.[2021]

Nicotine replacement therapy (NRT) significantly increases the chances of quitting smoking by 50% to 60%, based on a systematic review of 136 studies involving 64,640 participants, demonstrating its effectiveness across various forms like gum, patches, and sprays.

While NRT can cause minor side effects such as skin irritation and mouth discomfort, serious adverse events are extremely rare, indicating that NRT is a safe option for those trying to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine replacement therapy versus control for smoking cessation. Hartmann-Boyce, J., Chepkin, SC., Ye, W., et al.[2022]

In a crossover trial with 27 smokers, the combination of nicotine replacement therapies (NRTs) showed varying effects on craving and withdrawal, with the double patch leading to increased urges to smoke compared to other combinations.

The combination of lozenges or gums with a patch did not significantly increase craving or withdrawal scores, suggesting that these combinations may provide better relief from withdrawal symptoms when chosen by the user.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of craving and withdrawal among four combination nicotine treatments. Schneider, NG., Cortner, C., Gould, JL., et al.[2017]

A meta-analysis of 53 randomized controlled trials involving 17,703 subjects found that nicotine-replacement therapy (NRT) significantly increases the odds of smoking abstinence, with an overall odds ratio of 1.71 compared to control groups.

Different forms of NRT showed varying effectiveness, with inhaled nicotine being the most effective (odds ratio of 3.05), while the effectiveness was largely independent of the level of nicotine dependence and the intensity of additional support provided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. Silagy, C., Mant, D., Fowler, G., et al.[2019]

In a study involving 47 dependent adult smokers, both the Zonnic nicotine mouth spray and lozenge significantly reduced cravings more than a placebo, with the mouth spray providing the fastest relief within five minutes.

The mouth spray also achieved higher maximum blood nicotine levels and faster absorption compared to the lozenge and nicotine gum, indicating its potential effectiveness for acute craving relief in smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfaction. McRobbie, H., Thornley, S., Bullen, C., et al.[2015]

A study involving 324 smokers showed that high-dose nicotine patches (35 mg) significantly reduced withdrawal symptoms and cravings during smoking cessation, using real-time assessments with electronic diaries.

The active nicotine patches not only decreased withdrawal severity but also completely eliminated some symptoms related to deprivation, such as changes in mood and concentration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy. Shiffman, S., Ferguson, SG., Gwaltney, CJ., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Preferences among four combination nicotine treatments. [2018]

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

Impact of a Temporary NRT Enhancement in a State Quitline and Web-Based Program. [2019]

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

The use of nicotine replacement therapy for smoking reduction and temporary abstinence: an interview study. [2022]

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

Flexible, dual-form nicotine replacement therapy or varenicline in comparison with nicotine patch for smoking cessation: a randomized controlled trial. [2018]

5. Germany pubmed.ncbi.nlm.nih.gov

A comparison of the abuse liability and dependence potential of nicotine patch, gum, spray and inhaler. [2022]

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

High-dose transdermal nicotine replacement for tobacco cessation. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Adverse effects with use of nicotine replacement therapy among quitline clients. [2015]

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

Regulation of nicotine replacement therapies (NRT): a critique of current practice. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Patterns and predictors of nicotine replacement therapy use among alcohol and other drug clients enrolled in a smoking cessation randomised controlled trial. [2021]

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

Nicotine replacement therapy versus control for smoking cessation. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Comparison of craving and withdrawal among four combination nicotine treatments. [2017]

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

Meta-analysis on efficacy of nicotine replacement therapies in smoking cessation. [2019]

13. England pubmed.ncbi.nlm.nih.gov

A randomized trial of the effects of two novel nicotine replacement therapies on tobacco withdrawal symptoms and user satisfaction. [2015]

14. Germany pubmed.ncbi.nlm.nih.gov

Reduction of abstinence-induced withdrawal and craving using high-dose nicotine replacement therapy. [2019]