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

1200 Participants Needed

Trial Summary

What is the purpose of this trial?

The Free Samples for Health (FreSH) study tests whether providing free samples of stop smoking medicine called nicotine replacement therapy at dental visits results in a greater number of people quitting smoking than providing a gift of equal value (an electric toothbrush).

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.

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

Research shows that nicotine replacement therapies, like nicotine patches and lozenges, can almost double the chances of successfully quitting smoking. Different forms of these therapies, such as patches and lozenges, have been found to be effective, with individual preferences playing a role in their success. ^{1 2 3 4 5}

Is nicotine replacement therapy safe for humans?

Nicotine replacement therapy, like nicotine patches and lozenges, is generally considered safe for humans, with studies showing minimal cardiovascular side effects. However, physical activity may affect nicotine release from patches, potentially leading to higher nicotine levels, so it's important to follow usage instructions carefully. ^{3 6 7 8 9}

How does the nicotine lozenge and patch treatment differ from other smoking cessation drugs?

The nicotine lozenge and patch provide a steady release of nicotine to help reduce cravings and withdrawal symptoms, with the lozenge offering a more immediate effect compared to the slower-acting patch. This combination can be more flexible and satisfying for some users compared to other nicotine replacement options like gum or nasal sprays. ^{3 4 10 11 12}

Research Team

Sandra Japuntich

Principal Investigator

Hennepin Healthcare/University of Minnesota Medical School

Eligibility Criteria

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.

I am 18 years old or older.

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Nicotine patch vs. nicotine lozenge for smoking cessation: an effectiveness trial coordinated by the Community Clinical Oncology Program. [2022]

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

Pharmacokinetic Characterization of a Prototype Mini Nicotine Lozenge. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetic characterization of three novel 4-mg nicotine lozenges . [2018]

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

A randomised study to assess the nicotine pharmacokinetics of an oral nicotine pouch and two nicotine replacement therapy products. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, safety and efficacy from randomized controlled trials of 1 and 2 mg nicotine bitartrate lozenges (Nicotinell). [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of nicotine and cotinine after application of two different nicotine patches under steady state conditions. [2015]

7. Australia pubmed.ncbi.nlm.nih.gov

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

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

Pharmacokinetic disposition of multiple-dose transdermal nicotine in healthy adult smokers. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

Effect of exercise on transdermal nicotine release in healthy habitual smokers. [2019]

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

The future of nicotine replacement. [2019]

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

Efficacy of a nicotine nasal spray in smoking cessation: a placebo-controlled, double-blind trial. [2019]

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

Comparative efficacy of 24-hour and 16-hour transdermal nicotine patches for relief of morning craving. [2019]