Timing of Nicotine Replacement Therapy for Smoking Cessation

(MC-NRT Trial)

Overseen By Laurie A Zawertailo, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 4

Sponsor: Centre for Addiction and Mental Health

Must be taking: Nicotine replacement

Must not be taking: Hormones, Smoking cessation

Disqualifiers: Pregnancy, Cannabis, Tobacco, Psychiatric, 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: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to help women quit smoking by exploring the optimal timing for starting nicotine replacement therapy (NRT) based on their menstrual cycle. Researchers seek to determine if beginning a quit attempt in the first half of the cycle (the follicular phase) improves success compared to starting later or at a random time. Women with regular menstrual cycles who smoke at least five cigarettes a day may be suitable for this study. Participants will receive nicotine patches and gum or lozenges, along with behavioral support, to aid their quit attempt. As a Phase 4 trial, this study uses FDA-approved treatments to understand how they can benefit more patients.

Will I have to stop taking my current medications?

If you are currently using nicotine replacement therapy or other smoking cessation medications, you will need to stop taking them to participate in this trial. Additionally, if you are using hormonal treatments like progesterone, estrogen, testosterone, or fertility treatments, you will also need to stop.

What is the safety track record for these treatments?

Research shows that nicotine replacement therapy (NRT) is generally safe and well-tolerated. This treatment helps individuals quit smoking by reducing cravings and withdrawal symptoms. Studies have found that NRT can effectively aid smoking cessation. However, some users might experience mild and temporary side effects like headaches, nausea, or dizziness.

The FDA has approved NRT products to help people quit smoking, and they can even double the chances of success. However, using them while still smoking can cause harmful effects. Those considering joining a trial or using NRT should consult a healthcare provider about any concerns. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about this trial because it explores the timing of nicotine replacement therapy (NRT) in relation to the menstrual cycle, which is a fresh approach to smoking cessation. While standard treatments, like nicotine patches or gum, focus solely on delivering nicotine to reduce withdrawal symptoms, this trial investigates whether starting NRT at specific phases of the menstrual cycle—mid-luteal or mid-follicular—can enhance quitting success rates. This approach is unique because it considers hormonal fluctuations that might impact cravings and withdrawal, potentially leading to more personalized and effective smoking cessation strategies for women.

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

Research shows that nicotine replacement therapy (NRT) helps people quit smoking by reducing cravings and withdrawal symptoms. Studies have found that tools like nicotine gum or patches can improve the chances of quitting successfully. This trial examines when to start NRT to help more women quit smoking. Specifically, participants will be assigned to different treatment arms to determine if starting NRT at various times in the menstrual cycle (MC) eases quitting. One arm will begin NRT during the mid-follicular phase, another during the mid-luteal phase, and a third will follow usual care with randomly selected target quit dates. Starting during the mid-follicular phase might be particularly beneficial. Early evidence suggests that timing could be crucial, making this a promising approach to increase quitting success. ^{1 3 5 6 7}

Who Is on the Research Team?

Laurie Zawertailo, PhD

Principal Investigator

Centre for Addiction and Mental Health

Are You a Good Fit for This Trial?

This trial is for Canadian women who smoke at least 5 cigarettes daily, have regular menstrual cycles without hormonal contraception use in the past 6 months, and are planning to quit smoking soon. They must be willing to try nicotine replacement therapy (patches/gum/lozenge) and not have severe health issues like recent heart attacks or unstable psychiatric conditions.

Inclusion Criteria

I am willing and able to use nicotine patches and gum or lozenges to quit smoking.

I have smoked at least 5 cigarettes daily for the last 6 months.

Stated willingness to comply with all study procedures

Exclusion Criteria

I am currently using hormone or fertility treatments.

I do not have severe heart rhythm problems or worsening chest pain.

I have used hormonal contraceptives in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive nicotine replacement therapy (NRT) and behavioral support for 6 weeks, starting on their target quit date (TQD) based on menstrual cycle phase

6 weeks

Online program with app and email support

Follow-up

Participants are monitored for smoking abstinence and quit success at 7 days, end of treatment, and 6 months post-target quit date

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Replacement Therapy Agent
• Timing of nicotine replacement therapy start date

Trial Overview The study tests if timing the start of a quit attempt with nicotine replacement therapy to certain phases of the menstrual cycle affects success rates. It compares starting during the follicular phase versus luteal phase or at any time without considering the cycle.

How Is the Trial Designed?

Group I: Mid-Luteal Phase Target Quit Date Experimental Treatment 2 Interventions

Participants will start their quit attempts during the mid-luteal phase of their MC (6-8 days pre-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Group II: Mid-Follicular Phase Target Quit Date Experimental Treatment 2 Interventions

Participants will start their quit attempts during the mid-follicular phase of their MC (6-8 days post-onset of menses). Each participant will be provided with a range of appropriate dates based on the information about their menstrual cycle, and they will select a target quit date from the range. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Group III: Randomly Selected Target Quit Date (Usual Care) Active Control 1 Intervention

Participants will start their quit attempts within 30 days of their enrollment into the study. They will select their target quit dates without regard for their MC. Participants will be receiving NRT and will have access to behavioral support for the following 6 weeks.

Nicotine Replacement Therapy Agent is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Nicotine Replacement Therapy for:

• Smoking cessation

Approved in United States as Nicotine Replacement Therapy for:

• Smoking cessation

Approved in Canada as Nicotine Replacement Therapy for:

• Smoking cessation

Approved in Japan as Nicotine Replacement Therapy for:

• Smoking cessation

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Canadian Cancer Society (CCS)

Collaborator

Trials

84

Recruited

42,100+

Published Research Related to This Trial

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]

Nicotine replacement therapy (NRT) is safe and effective, but it is often used incorrectly; providing clear instructions and adequate dosing is crucial for maximizing its benefits.

Combining different forms of NRT, such as using a nicotine patch with gum or lozenges, and starting the patch two weeks before quitting can significantly improve quit rates and help prevent relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimising nicotine replacement therapy in clinical practice. Mendelsohn, C.[2018]

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]

Nicotine replacement therapy (NRT) is effective for smoking cessation, but many users do not achieve long-term abstinence, suggesting a need for personalized treatment approaches.

Tailoring NRT to individual smokers' needs and preferences, potentially using genetic profiling, could improve treatment outcomes and safety, addressing the variability in response to standard NRT formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tailoring nicotine replacement therapy: rationale and potential approaches. McClure, JB., Swan, GE.[2018]

A study involving 30 smokers using a 2 mg sublingual nicotine tablet for 3-6 months found that it has a good safety profile, with only mild and transient oral mucosal effects, primarily melanin pigmentation.

After 6 months, most oral lesions observed during treatment resolved, indicating that the sublingual tablet is a safe option for nicotine replacement therapy in smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The long-term effect of nicotine on the oral mucosa. Wallström, M., Sand, L., Nilsson, F., et al.[2023]

Cessation of smoking significantly reduces the risk of cardiovascular events, and nicotine replacement therapy (NRT) is an effective tool to help individuals quit smoking.

The article reviews the safety of NRT, concluding that it is safer than continued smoking, even for patients with existing cardiovascular disease, and provides recommendations for its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine replacement therapy and cardiovascular disease. Ford, CL., Zlabek, JA.[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]

Nicotine replacement therapies (NRTs) significantly increase the chances of quitting smoking, with an overall odds ratio of 1.71 based on a review of 53 trials involving 17,703 patients.

Among different NRT forms, the transdermal patch and inhaled nicotine showed the highest effectiveness, with odds ratios of 2.07 and 3.05 respectively, indicating that these methods may be particularly beneficial for smokers trying to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of nicotine replacement therapies in smoking cessation. Silagy, C., Mant, D., Fowler, G., et al.[2019]

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]

Nicotine replacement therapy (NRT) significantly increases the chances of quitting smoking, with an odds ratio of 1.72 compared to control, and is effective across various forms including gum, patches, and nasal sprays, regardless of the level of additional support provided.

While all forms of NRT are effective, the study suggests that bupropion may be more effective than NRT alone or in combination, indicating that alternative pharmacotherapies could enhance smoking cessation efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine replacement therapy for smoking cessation. Silagy, C., Mant, D., Fowler, G., et al.[2018]

Mucoadhesive nicotine tablets can effectively deliver nicotine in a controlled manner, helping individuals gradually reduce their dependence on smoking.

The best formulation for these tablets was found to be a mixture of Hydroxypropyl Methylcellulose (HPMC 50cps) and Carbopol 934, which provided optimal adhesiveness and a stable release rate of nicotine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation of nicotine mucoadhesive tablet for smoking cessation and evaluation of its pharmaceuticals properties. Bahri-Najafi, R., Rezaei, Z., Peykanpour, M., et al.[2021]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK493148/

Nicotine Replacement Therapy - StatPearls - NCBI Bookshelf NRTs are designed to replicate the nicotine response typically experienced through smoking, thereby helping individuals manage cravings and withdrawal symptoms.

2. cancer.org cancer.org/cancer/risk-prevention/tobacco/guide-quitting-smoking/nicotine-replacement-therapy.html

Nicotine Replacement Therapy to Help You Quit Tobacco Nicotine gum is usually recommended for 6 to 12 weeks, with the maximum being 6 months. Tapering down the amount of gum you use as you approach ...

3. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK279221/

Smoking: Learn More – How effective is nicotine replacement ... Nicotine gum and patches can relieve these symptoms, increasing the likelihood of successfully quitting smoking.

4. cdc.gov cdc.gov/tobacco/campaign/tips/quit-smoking/quit-smoking-medications/how-to-use-quit-smoking-medicines/how-to-use-the-nicotine-lozenge.html

How to Use Nicotine Lozenges | Quit Smoking The nicotine lozenge is an FDA-approved medicine that can help people quit smoking. It can be used every 1-2 hours by itself to control withdrawal symptoms (up ...

5. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/nicotine-replacement-therapy-nrt

Nicotine Replacement Therapy (NRT) NRT can help with physical withdrawal and craving symptoms. But it doesn't address every part of quitting smoking, like the mental, emotional ...

6. tobaccoinduceddiseases.org tobaccoinduceddiseases.org/Adverse-events-associated-with-nicotine-replacement-therapy-NRT-for-smoking-cessation,65973,0,2.html

Adverse events associated with nicotine replacement ... Nicotine replacement therapy (NRT) is the most common form of smoking cessation pharmacotherapy and has proven efficacy for the treatment of tobacco dependence.

7. fda.gov fda.gov/consumers/consumer-updates/want-quit-smoking-fda-approved-and-fda-cleared-cessation-products-can-help

Want to Quit Smoking? FDA-Approved Cessation Products ... Smoking cessation products approved or cleared by the FDA are shown to help people quit smoking and can even double your chance of quitting ...