SREC + Nicotine Lozenge for Smoking Cessation

Overseen By Irina Stepanov, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Masonic Cancer Center, University of Minnesota

Must not be taking: Anti-inflammatories, Metabolic enzyme-affecting

Disqualifiers: Nicotine products, Immune disorders, Respiratory diseases, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

125 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new e-cigarette developed by the National Institute on Drug Abuse to determine if it can help smokers reduce smoking-related risks. Researchers aim to understand the effects of switching from regular cigarettes to this standardized e-cigarette (Standardized Research E-cigarette, or SREC) or a nicotine lozenge. Individuals who smoke at least 5 cigarettes a day and haven't attempted to quit seriously in the last 3 months might be suitable candidates. The trial's ultimate goal is to gather data on how these products affect smokers' exposure to harmful chemicals. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new e-cigarette.

Do I have to stop taking my current medications for the trial?

The trial requires that you do not take anti-inflammatory medications or any medications that affect relevant metabolic enzymes. If you are on such medications, you may need to stop them to participate.

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

Research shows that the safety of the Standardized Research E-cigarette (SREC) remains under investigation. Few studies have gathered detailed safety information on its effects on heart or lung health, resulting in limited knowledge about its long-term impact on these areas.

Conversely, studies have found that the nicotine mini-lozenge is generally well-tolerated. One study showed that participants used the lozenge for up to a year without major problems. Additionally, the nicotine lozenge is already approved for helping people quit smoking, indicating its safety when used as directed.

Prospective trial participants should be aware that the SREC is still in early testing, so its safety is not yet fully understood. However, the nicotine mini-lozenge has a more established safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer potential new ways to help people quit smoking. The Standardized Research E-cigarette (SREC) provides a controlled and possibly less harmful way to satisfy nicotine cravings compared to traditional cigarettes. Meanwhile, the nicotine mini-lozenge offers a discreet and portable option for nicotine replacement that can be used at any time. Both methods aim to reduce or eliminate the harmful effects of smoking by either replacing cigarettes with e-cigarettes or using a lozenge to manage cravings, which could make quitting smoking more manageable and appealing.

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

Research has shown that e-cigarettes, such as the Standardized Research E-cigarette (SREC) used in this trial, can help people quit smoking more effectively than traditional methods like nicotine patches. One study found that individuals using e-cigarettes were more likely to stop smoking after six months compared to those using other methods. Similarly, nicotine mini-lozenges, another treatment option in this trial, can also aid in smoking cessation. Studies indicate that individuals using the lozenge are 2.1 to 3.7 times more likely to quit after six weeks. Both the SREC and nicotine mini-lozenges offer promising options for those trying to quit smoking in this trial. ^{6 7 8 9 10}

Who Is on the Research Team?

Irina Stepanov, PhD

Principal Investigator

University of Minnesota, Division of Environmental Health Sciences

Are You a Good Fit for This Trial?

This trial is for adult smokers aged 18-65 who smoke more than 5 cigarettes daily, have been smoking for at least a year, and haven't tried to quit in the last 3 months. Participants must be in good physical and mental health, not use other tobacco or nicotine products, and agree to switch completely to e-cigarettes or nicotine lozenges. Pregnant women or those on certain medications are excluded.

Inclusion Criteria

I am not pregnant, nursing, or planning to become pregnant.

Biochemically confirmed regular smoking status by a NicAlert test level of 6

I smoke 5 or more cigarettes daily and don't use other tobacco products.

Exclusion Criteria

Unstable living environment that would compromise the ability to attend visits, sequester study products or complete study procedures outside of visits

I have not tested positive for restricted drugs or failed the temperature test for the sample.

I use tobacco or nicotine products regularly, but not cigarettes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants switch from smoking cigarettes to using the Standardized Research E-cigarette (SREC) or nicotine mini-lozenge

8 weeks

Regular visits for monitoring and data collection

Follow-up

Participants are monitored for safety and effectiveness after treatment, with focus on biomarkers and product use

1 year

What Are the Treatments Tested in This Trial?

Interventions

• Nicotine Mini-Lozenge
• Standardized Research E-cigarette (SREC)

Trial Overview The study tests the toxic and carcinogenic potential of a Standardized Research E-cigarette (SREC) compared with Nicotine Mini-Lozenge. It aims to provide reference data on chemical exposures when regular smokers switch from traditional cigarettes to SRECs or medicinal nicotine.

How Is the Trial Designed?

Group I: Switching from Smoking Cigarettes to SREC Experimental Treatment 1 Intervention

Group II: Switching from Smoking Cigarettes to Nicotine Mini-Lozenge Experimental Treatment 1 Intervention

Group III: Usual Brand Cigarettes Active Control 1 Intervention

Who Is Running the Clinical Trial?

Masonic Cancer Center, University of Minnesota

Lead Sponsor

Trials

285

Recruited

15,700+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

This study involves 280 low socioeconomic status smokers to evaluate the effects of switching from high nicotine cigarettes to reduced nicotine content (RNC) cigarettes over 18 weeks, aiming to see if they can reduce smoking frequency without negative health impacts.

The primary goal is to assess whether these smokers can adhere to using only RNC cigarettes and whether this approach leads to lower nicotine dependence and reduced exposure to harmful tobacco smoke biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced nicotine content cigarettes in smokers of low socioeconomic status: study protocol for a randomized control trial. Krebs, NM., Allen, SI., Veldheer, S., et al.[2023]

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 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]

Smokers who switched to JUUL-brand electronic nicotine delivery systems (ENDS) for an average of 3 years showed significantly lower levels of harmful and potentially harmful constituents (HPHCs) compared to those who continued smoking cigarettes, indicating a reduction in exposure to toxic substances.

The study found that Switchers had lower markers of inflammation and respiratory symptoms, as well as reduced dependence on nicotine, suggesting that switching to JUUL may lower health risks associated with smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing Adult Smokers who Switched to JUUL vs Continuing Smokers: Biomarkers of Exposure and of Potential Harm and Respiratory Symptoms. Shiffman, S., Oliveri, DR., Goldenson, NI., et al.[2023]

E-cigarettes may help reduce cigarette consumption and could be as effective for smoking cessation as nicotine patches, based on a review of 7 studies from a larger pool of 169 publications.

There is currently no significant difference in adverse event rates between e-cigarettes and nicotine patches, but more extensive research is needed to fully understand their safety and efficacy for quitting smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarettes in North America: history, use, and implications for smoking cessation. Franck, C., Budlovsky, T., Windle, SB., et al.[2018]

Electronic cigarettes are popular among patients as a smoking cessation aid, but they are not approved by the FDA due to concerns about manufacturing practices and the presence of carcinogens.

While some studies suggest that e-cigarettes may help users reduce or quit traditional cigarette smoking, many of these studies have biases, and more rigorous research is needed to confirm their safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarettes: do they have a role in smoking cessation? Odum, LE., O'Dell, KA., Schepers, JS.[2022]

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]

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]

In a study involving 49 young adult e-cigarette users, compliance with using a standardized e-cigarette device and assigned e-liquid flavors significantly declined after the first week, indicating challenges in maintaining protocol adherence over time.

The correlation between nicotine intake (measured by serum cotinine levels) and e-cigarette use metrics (like puff count and duration) was strong in the first week but weakened in subsequent weeks, suggesting that simply assigning devices and flavors may not be enough to ensure consistent use in research settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Compliance in Controlled E-cigarette Studies. Rebuli, ME., Liu, F., Urman, R., et al.[2021]

The study found that the ECX-Joyetech E-Vic Mini exposure equipment does not consistently produce aerosols that meet the necessary conditions for reliable preclinical studies, particularly with low subohm resistance coils.

To ensure accurate risk assessments of e-cigarettes, the equipment's performance must be improved, especially by increasing airflow for certain coils, as current results may not be trustworthy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical and chemical characterizations of a reference e-cigarette used in animal testing. Soulet, S., Constans, L., Quinty, V.[2023]

Participants in the study generally had positive experiences using nicotine-containing e-cigarettes for smoking cessation, finding them helpful in managing nicotine cravings, especially when compared to nicotine replacement therapy (NRT).

Despite the positive feedback, there were concerns about the potential for developing a vaping habit as a replacement for smoking addiction, highlighting the need for further research on the long-term use of e-cigarettes as a quit aid.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Participant Experiences of a Quit Smoking Attempt Through Either Nicotine Replacement Therapy (NRT) Methods or the Use of an E-cigarette. Jones, G., McIntosh, E., Brose, LS., et al.[2022]

E-cigarettes have been shown to significantly reduce the desire to smoke and the number of cigarettes smoked per day in small clinical studies, suggesting they may help modify smoking habits.

While e-cigarettes may have fewer adverse effects compared to nicotine patches and can aid in short-term smoking reduction, there is limited evidence for their long-term effectiveness in achieving sustained smoking cessation beyond 6 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of electronic cigarettes for smoking cessation. Orr, KK., Asal, NJ.[2018]

In a randomized trial involving 68 adult smokers, those using electronic nicotine delivery systems (ENDS) showed a significant reduction in cigarette smoking compared to a control group, indicating potential efficacy in smoking cessation.

Participants using the higher nicotine (24 mg) ENDS were more likely to continue using the product and make independent purchases, suggesting that higher nicotine delivery may enhance user engagement and support smoking reduction efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Naturalistic, Randomized Pilot Trial of E-Cigarettes: Uptake, Exposure, and Behavioral Effects. Carpenter, MJ., Heckman, BW., Wahlquist, AE., et al.[2018]

A systematic review of six randomized controlled trials found no significant difference in smoking cessation rates between electronic nicotine delivery systems (ENDS) and traditional nicotine replacement therapies (NRT), indicating that ENDS may not be more effective for quitting smoking.

The overall quality of evidence was rated as low or very low, highlighting the need for further research to better understand the effectiveness and safety of ENDS compared to NRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Smoking cessation in individuals who use vaping as compared with traditional nicotine replacement therapies: a systematic review and meta-analysis. Pound, CM., Zhang, JZ., Kodua, AT., et al.[2023]

A systematic review of 29 studies found low certainty that the flavor of electronic nicotine delivery systems (ENDS) influences the intention to quit smoking or the likelihood of making a quit attempt.

The evidence regarding the impact of nontobacco versus tobacco/unflavored ENDS on smoking cessation success is very low, indicating that more high-quality research is needed to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of flavored electronic nicotine delivery systems in smoking cessation: A systematic review. Liber, AC., Knoll, M., Cadham, CJ., et al.[2023]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK195719/

SUMMARY OF EVIDENCE - Nicotine Replacement Therapy ... In total, based on eight RCTs including 5101 smokers, smokers with high dose patches (>22mg) achieved statistically significant more smoking cessation than that ...

2. 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 ...

3. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/211489

Efficacy of a Nicotine Lozenge for Smoking Cessation The odds of being abstinent after 6 weeks of treatment were 2.1 to 3.7 times greater among those receiving the active lozenge (2- and 4-mg doses ...

4. haleonhealthpartner.com haleonhealthpartner.com/en-us/respiratory-health/brands/nicotine-replacement-therapy/nicorette-mini-lozenges/nicorette-mini-lozenges-efficacy/

Nicorette mini Lozenges Efficacy | Haleon HealthPartners Learn about efficacy and cessation rates of smokers using Nicorette mini Lozenges. Get the information you need from Haleon Oral HealthPartner.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02564315?titles=long%20term%20quitting&rank=1

The Long-Term Quitting (Smoking Cessation) Study All RR Cessation Phase participants will receive 8 weeks of combination nicotine replacement therapy (nicotine patch + nicotine mini-lozenge). The investigators ...

6. haleonhealthpartner.com haleonhealthpartner.com/en-us/respiratory-health/brands/nicotine-replacement-therapy/nicorette-lozenges/safety-information/

Nicorette Lozenges Safety Information The Nicorette Lozenge was found to be well tolerated. 1 Safety was evaluated in a randomized, double-blind, placebo-controlled clinical trial over 52 weeks.

7. medsafe.govt.nz medsafe.govt.nz/profs/datasheet/n/nicorettecooldrops.pdf

Data Sheet NICORETTE® Cooldrops Lozenges 2 mg are suitable for smokers with a low nicotine dependency e.g. those smoking their first cigarette of the day more.

8. dailymed.nlm.nih.gov dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=237471f8-ce0f-423b-993f-b4380fd890ff

Label: MINI NICOTINE- nicotine polacrilex lozenge - DailyMed TO INCREASE YOUR SUCCESS IN QUITTING: 1. You must be motivated to quit. 2.Use Enough - Use at least 9 Nicotine mini lozenges per day during the first six weeks.

9. nicorette.ca nicorette.ca/products/lozenge

NICORETTE® Smoking Cessation Lozenge If you smoke 25 cigarettes or fewer a day, use the 2 mg lozenge. If you smoke more than 25 cigarettes a day, use the 4 mg lozenge.

10. reference.medscape.com reference.medscape.com/drug/nicorette-lozenge-nicotine-lozenge-999318

nicotine lozenge (OTC) Smoking Cessation. Weeks 1-6: 1 lozenge q1-2hr. Weeks 7-9: 1 lozenge q2-4hr. Weeks 10-12: 1 lozenge q4-8hr. Do not exceed >5 lozenges/6hr.