Nicotine Replacement Therapy for Smoking Cessation

(CAN-DOSE Trial)

Overseen By Rachel Christian

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Medical University of South Carolina

Must be taking: Nicotine replacement

Must not be taking: Smoking cessation

Disqualifiers: Pregnancy, Cardiac arrhythmia, Angina, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of nicotine patches and lozenges in helping people quit smoking and vaping. It compares different doses to determine if a higher dose is more effective. Suitable participants include those who use e-cigarettes daily, smoke regularly, and wish to quit within the next month. Participants should reside in South Carolina and be willing to use nicotine replacement therapy. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, allowing participants to contribute to important findings.

Will I have to stop taking my current medications?

The trial requires that you do not use other nicotine-containing products or smoking cessation medications while participating.

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

Research has shown that nicotine replacement therapy, such as patches and lozenges, is generally safe. One study found that even high-dose nicotine patches are well-tolerated, though some individuals might experience side effects like skin irritation or dizziness. For regular doses, using at least 9 and up to 20 lozenges daily is recommended and has proven effective and safe for those trying to quit smoking. Both higher and regular doses have been used safely before, but monitoring for any unusual symptoms and reporting them to a healthcare provider is important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer new ways to enhance nicotine replacement therapy (NRT) for smoking cessation. Unlike standard options that typically use a single patch or lozenge, these treatments explore combinations like using an augmented dose with either a 14mg or an additional 21mg patch, alongside 4mg lozenges. This approach aims to better manage withdrawal symptoms by providing more consistent and higher doses of nicotine, potentially improving success rates for those trying to quit smoking. By offering varied dosing strategies, these treatments could cater to different levels of nicotine dependence, which is a new angle in NRT.

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

Research shows that nicotine replacement therapy (NRT), such as patches and lozenges, can help people quit smoking and vaping. This trial will compare different dosing strategies of NRT. Participants in Arm A will receive a regular dose of a 21mg patch and 4mg lozenges. Arm B will involve an augmented dose with a 21mg patch, an additional 14mg patch, and 4mg lozenges. Arm C will test a higher dose with two 21mg patches and 4mg lozenges. Studies suggest that higher doses of NRT may effectively aid in quitting both cigarettes and e-cigarettes. Specifically, one study found that people who used NRT for 8 weeks had higher success rates (42.5%) compared to those who used it for only 4 weeks. Additionally, using nicotine patches or lozenges for a longer duration has been linked to better results in heavy smokers. Overall, both regular and higher doses of NRT appear to support quitting smoking. ^{1 2 4 6 7}

Who Is on the Research Team?

Amanda Palmer

Principal Investigator

Medical University of South Carolina

Are You a Good Fit for This Trial?

The CAN-DOSE study is for adults over 18 who use nicotine e-cigarettes daily and smoke cigarettes weekly, wanting to quit both within a month. They must be willing to use nicotine replacement therapy (NRT) and have no medical conditions that make NRT unsafe, like recent heart issues or pregnancy.

Inclusion Criteria

E-cigarette use 5+ times/day

Mailing address in SC.

Willingness to use NRT

Exclusion Criteria

I do not have heart issues, uncontrolled vascular disease, or conditions affected by phenylalanine.

Individuals reporting current use of other nicotine-containing products and/or smoking cessation medications

Those who vape non-nicotine substances

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive varying doses of nicotine replacement therapy to aid in quitting smoking and vaping

8 weeks

Daily diary assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Augmented Nicotine patch and lozenge dose
• Regular Nicotine patch and lozenge dose

Trial Overview This study tests whether using nicotine patches and lozenges can help people stop smoking and vaping. It compares the effectiveness of regular versus higher doses of these medications in aiding cessation.

How Is the Trial Designed?

Group I: Arm A Active Control 1 Intervention

21mg patch, qd + 4mg lozenge prn \[minimum of 5 \& up to 20 per day\]

Group II: Arm B Active Control 1 Intervention

21mg patch + 14mg patch qd + 4mg lozenge prn minimum of 5 \& \[up to 30 per day\]

Group III: Arm C Active Control 1 Intervention

2 x 21mg patches qd + 4mg lozenges prn \[minimum of 5 \& up to 40 per day\]

Who Is Running the Clinical Trial?

Medical University of South Carolina

Lead Sponsor

Trials

994

Recruited

7,408,000+

American Cancer Society, Inc.

Collaborator

Trials

237

Recruited

110,000+

Published Research Related to This Trial

The study found that three prototype 4-mg nicotine lozenges produced in India were bioequivalent to the globally marketed Nicorette® 4-mg lozenge, indicating they can effectively deliver similar levels of nicotine to the bloodstream.

All prototype lozenges were well tolerated and had safety profiles comparable to the reference product, suggesting they are a safe alternative for nicotine replacement therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . Sukhija, M., Srivastava, R., Kaushik, A.[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]

In a study of 84,667 patients in a smoking cessation program, it was found that the prescribed doses of nicotine replacement therapy (NRT) did not increase adequately with the number of cigarettes smoked per day, leading to potential under-treatment.

Patients who received initial NRT doses below 2 mg per cigarette per day had poorer cessation outcomes, suggesting that higher doses may be necessary for heavy smokers to improve their chances of quitting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adequacy of nicotine replacement and success quitting tobacco in clinical populations: An observational study. Veldhuizen, S., Behal, A., Zawertailo, L., et al.[2023]

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]

Nicotinell lozenges, particularly the 1 mg formulation, have been shown to be bioequivalent to 2 mg nicotine gum, providing effective nicotine delivery for smoking cessation, with significant short-term efficacy demonstrated in over 900 smokers.

The lozenges have an excellent safety profile, with only mild and reversible adverse events reported, making them a safe option for smokers seeking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell). Dautzenberg, B., Nides, M., Kienzler, JL., et al.[2023]

In a study of 400 smokers, using a nicotine inhaler combined with a nicotine patch led to significantly higher smoking cessation rates compared to using the inhaler with a placebo patch, with 60.5% abstinence at 6 weeks versus 47.5%.

The combination therapy not only improved cessation rates but also showed a trend toward better lung function and reduced respiratory symptoms in those who quit smoking, indicating its potential benefits for overall respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine inhaler and nicotine patch as a combination therapy for smoking cessation: a randomized, double-blind, placebo-controlled trial. Bohadana, A., Nilsson, F., Rasmussen, T., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40409566/

Augmented Doses of Nicotine Replacement Therapy Conclusions: Augmented doses of nicotine replacement therapy are a feasible, promising treatment for dual cessation of combustible cigarettes and e-cigarettes.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0749379725001564

Augmented Doses of Nicotine Replacement Therapy Conclusions. Augmented doses of nicotine replacement therapy are a feasible, promising treatment for dual cessation of combustible cigarettes and e-cigarettes. ...

3. ajpmonline.org ajpmonline.org/article/S0749-3797(25)00156-4/abstract

Augmented Doses of Nicotine Replacement Therapy Conclusions. Augmented doses of nicotine replacement therapy are a feasible, promising treatment for dual cessation of combustible cigarettes ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2834192/

Nicotine Patch vs. Nicotine Lozenge for Smoking Cessation However, only 20-25% of smokers who use transdermal nicotine or nicotine lozenges report abstinence 6-months after a quit date (Shiffman et al., 2002a; Stead et ...

5. withpower.com withpower.com/trial/phase-2-smoking-cessation-10-2023-5552a

Nicotine Replacement Therapy for Smoking Cessation 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%) ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0025619620313872

Frequently Reported Adverse Events With Smoking ... To compare the incidence, severity, and clinical course of frequently reported adverse events (AEs) after treatment with smoking cessation pharmacotherapies.

7. medsafe.govt.nz medsafe.govt.nz/profs/class/Agendas/agen24-Nicotine-Lozenges.pdf

Nicotine Lozenges However even very small doses can be lethal in very young children, but this is also true for children eating cigarette butts and the lozenges will be in ...