Free Nicotine Replacement Therapy for Smoking

(FreSH Trial)

Overseen By Sandra Japuntich, Ph.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hennepin Healthcare Research Institute

Must not be taking: Tobacco cessation medication

Disqualifiers: No smartphone, Recent heart attack, 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: 3

Duration: 2 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether providing free nicotine replacement therapy, such as patches and lozenges, during dental visits helps people quit smoking more effectively than providing an electric toothbrush. The goal is to determine if these free samples enhance smoking cessation success. Participants will also receive advice on quitting and information on a state quitline for additional support. The trial seeks smokers who smoke at least once a day on most days of the month and have not recently used stop-smoking medications. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have used tobacco cessation medication in the past week.

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

Research has shown that nicotine lozenges are generally well tolerated. One study found no major safety issues over a year, indicating they are a safe choice for many trying to quit smoking. The FDA's approval of nicotine lozenges further supports their safety.

Similarly, nicotine patches are considered safe and effective for quitting smoking. Available without a prescription, they have helped many successfully quit. While some users might experience mild side effects, they are generally safe for most people.

Both treatments have a strong safety record, so prospective trial participants can feel confident about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Free Nicotine Replacement Therapy because it combines nicotine lozenges and patches with a personalized intervention method. Unlike standard nicotine replacement therapies that are often used in isolation, this approach integrates direct support from oral health practitioners who actively engage with participants about their smoking habits. Additionally, the inclusion of an electric toothbrush as a comparator highlights a novel consideration of oral health in smoking cessation. By combining behavioral support with nicotine replacement, this strategy aims to enhance motivation and adherence, potentially leading to better quit rates than traditional methods alone.

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

Research has shown that nicotine lozenges, which participants in this trial may receive, can significantly aid smoking cessation. One study found that people using nicotine lozenges were 2.1 to 3.7 times more likely to quit smoking after six weeks compared to those who did not use them. Nicotine patches, another treatment option in this trial, have also proven effective. Specifically, individuals using nicotine patches were more than twice as likely to quit smoking as those using a placebo patch. Both nicotine lozenges and patches have successfully helped smokers quit, offering promising options for those seeking to stop smoking. ^{2 4 6 7 8}

Who Is on the Research Team?

Sandra Japuntich

Principal Investigator

Hennepin Healthcare/University of Minnesota Medical School

Are You a Good Fit for This Trial?

This trial is for adults over 18 who smoke at least one cigarette daily on most days of the month. Participants must own a smartphone with internet and cannot join if they are pregnant, breastfeeding, had a recent heart attack or stroke, or used tobacco cessation meds recently.

Inclusion Criteria

I smoke at least one cigarette daily for most of the month.

Exclusion Criteria

Does not own a smartphone with internet access

Pregnant or breastfeeding

I have not had a heart attack or stroke in the last 3 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nicotine replacement therapy or an electric toothbrush as part of the Ask-Advise-Refer intervention

2 weeks

1 visit (in-person)

Follow-up

Participants are monitored for smoking abstinence and changes in perception of nicotine replacement therapy

6 months

2 visits (in-person) at 1 month and 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ask-Advise-Refer
• Nicotine lozenge
• Nicotine Patch, 14 Mg/24 Hr Transdermal Film, Extended Release

Trial Overview

The study compares the effectiveness of free nicotine replacement therapy (like lozenges and patches) given during dental visits versus receiving an electric toothbrush to see which helps more people quit smoking.

How Is the Trial Designed?

Group I: Nicotine Replacement Therapy Experimental Treatment 3 Interventions

Participants will receive the Ask-Advise-Refer intervention which includes an oral health practitioner asking about their tobacco use, advising them to quit smoking, and referring them to the state quitline. They will also receive a sample bag including information about smoking and oral health, the state quitline, and a two week supply of 14mg nicotine patches and 4mg lozenges.

Group II: Electric Toothbrush Active Control 1 Intervention

Participants will receive the Ask-Advise-Refer intervention which includes an oral health practitioner asking about their tobacco use, advising them to quit smoking, and referring them to the state quitline. They will also receive a sample bag including information about smoking and oral health, the state quitline, and an electric toothbrush.

Nicotine lozenge is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Nicorette Lozenge for:

• Smoking cessation

Approved in Canada as Nicotrol Lozenge for:

• Smoking cessation

Approved in European Union as Nicorette Lozenge for:

• Smoking cessation

Who Is Running the Clinical Trial?

Hennepin Healthcare Research Institute

Lead Sponsor

Trials

94

Recruited

77,100+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Northwestern University

Collaborator

Trials

1,674

Recruited

989,000+

HealthPartners Institute

Collaborator

Trials

196

Recruited

3,721,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

Kaiser Permanente

Collaborator

Trials

563

Recruited

27,400,000+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

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]

Transdermal nicotine release from two different nicotine patch formulations increases during physical activity, but this increase does not significantly affect overall plasma nicotine levels, indicating a consistent pharmacokinetic profile during rest and exercise.

In a study involving 10 healthy smokers, no adverse events were reported, suggesting that using transdermal nicotine patches during physical activity is safe and does not lead to toxic plasma concentrations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of exercise on transdermal nicotine release in healthy habitual smokers. Bur, A., Joukhadar, C., Klein, N., et al.[2019]

Transdermal nicotine therapy significantly increases the chances of quitting smoking, more than doubling success rates in motivated smokers who smoke at least 10-15 cigarettes per day, with an odds ratio of 2.3 after 12 months.

While effective, transdermal nicotine can cause side effects like skin reactions and sleep disturbances, and it is recommended primarily for smokers who struggle to quit through other methods due to its cost.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The pros and cons of transdermal nicotine therapy. Gourlay, S.[2015]

In a study of 642 smokers, transdermal nicotine showed a trend towards higher quit rates compared to nicotine lozenges, with 24.3% quitting at the end of treatment versus 18.7% for lozenges.

Smokers who preferred transdermal nicotine and did not use nicotine to manage emotional distress had better success rates, suggesting that individual preferences and reasons for smoking can influence treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine patch vs. nicotine lozenge for smoking cessation: an effectiveness trial coordinated by the Community Clinical Oncology Program. Schnoll, RA., Martinez, E., Tatum, KL., et al.[2022]

The prototype mini lozenge for nicotine replacement therapy (NRT) was found to be bioequivalent to a commercially available mini lozenge, showing no significant differences in key pharmacokinetic parameters such as maximum plasma nicotine concentration and overall nicotine absorption.

The most common side effect reported was mild throat irritation, with no serious adverse events, indicating that the new lozenge is a safe option for smokers seeking to manage withdrawal symptoms during their quit attempts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge. Lai, PM., Araga, M., Hamilton, A., et al.[2022]

A new nicotine nasal spray (NNS) significantly improved smoking cessation success rates compared to a placebo in a study of 255 smokers, with continuous abstinence rates showing marked differences at various intervals (e.g., 63% vs. 40% on day 5).

The NNS was found to be safe and well-tolerated, providing a faster-acting alternative to traditional nicotine replacement therapies, with side effects being common but manageable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial. Schneider, NG., Olmstead, R., Mody, FV., et al.[2019]

In a study involving 34 healthy adult smokers, tobacco-free oral nicotine pouches (NPs) showed similar nicotine absorption to lozenges and significantly better absorption than gum, indicating they may be an effective alternative for nicotine delivery.

Participants reported higher satisfaction with NPs compared to lozenges, and NPs had a lower incidence of minor adverse events, suggesting they are a well-tolerated option for smokers seeking nicotine replacement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products. Azzopardi, D., Ebajemito, J., McEwan, M., et al.[2022]

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]

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8 Nicotine Patch Side Effects and How to Manage Them

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