E-Cigarette Flavor Impact for ENDS Flavors

(RVA Flavors Trial)

Overseen By Caroline O Cobb, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Virginia Commonwealth University

Disqualifiers: Unstable medical condition, Illegal drug use, Pregnancy, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

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 explores how different electronic cigarette (e-cigarette) flavors, such as menthol and tobacco, affect smoking habits and exposure to harmful substances among African American smokers. Participants will try various e-cigarette flavors to assess changes in smoking behavior and potential addiction. Ideal candidates are African American menthol smokers who have smoked at least five cigarettes a day for over a year and have used e-cigarettes in the past three months. As an unphased study, this trial provides a unique opportunity to contribute to important research on smoking behaviors and health impacts.

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

The trial protocol does not specify whether you need to stop taking your current medications.

What prior data suggests that this study's methods are safe?

Research shows that electronic nicotine delivery systems (ENDS), such as tobacco-flavored e-cigarettes, expose users to harmful substances. These substances can increase the risk of lung diseases and lead to nicotine addiction. Studies have found that both tobacco-flavored and menthol-flavored liquids can harm the lungs.

Even unflavored e-cigarettes pose risks. Research indicates that unflavored e-liquids can cause lung inflammation and disrupt normal cell functions.

In summary, no completely safe option exists for ENDS, whether flavored or unflavored. The safest choice is to avoid using these products altogether. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it's exploring how different e-cigarette flavors might impact smoking behaviors. Unlike traditional options like nicotine patches or gum, which aim to reduce nicotine cravings, this trial focuses on how the availability of menthol, tobacco, or unflavored e-liquids can influence users' choices and habits. By comparing these specific flavor profiles, researchers hope to gain insights into how flavors affect the appeal and usage of e-cigarettes, potentially guiding future regulations and public health strategies.

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

This trial will compare the impact of different e-cigarette flavors on smoking habits. Participants in the Menthol+Tobacco arm will use both menthol and tobacco-flavored liquids for electronic nicotine delivery systems. Those in the Tobacco arm will use only tobacco-flavored liquid, while the Unflavored arm will use only unflavored liquid. Research has shown that tobacco-flavored e-cigarettes do not make quitting smoking easier than menthol-flavored ones. Some studies suggest that banning flavors can reduce vaping but might lead young adults to smoke more cigarettes. Little evidence supports that unflavored e-cigarettes help people quit smoking. Some believe unflavored options might cause less lung damage than flavored ones. Overall, the impact of flavor availability on smoking habits and quitting success remains unclear. ^{6 7 8 9 10}

Who Is on the Research Team?

Andrew J Barnes, PhD

Principal Investigator

Virginia Commonwealth University

Caroline O Cobb, PhD

Principal Investigator

Virginia Commonwealth University

Are You a Good Fit for This Trial?

This trial is for African American menthol cigarette smokers over 21 who smoke more than 5 cigarettes a day and have used electronic cigarettes in the last month. Participants should not plan to quit smoking soon, must be able to complete surveys, and have a mobile phone with text/data plans. Those using marijuana or other drugs frequently, pregnant women, or those with serious health issues can't join.

Inclusion Criteria

ENDS use in the past 3 months

Regular cigarette brand is flavored to taste like menthol or mint

Identify as Black/African American (single or multi-race)

Exclusion Criteria

I am not willing to use electronic nicotine delivery systems in the trial.

I have not had any serious or unstable health issues in the last year.

Report any other illegal drug use in the past 30 days

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive electronic nicotine delivery systems with different flavor options for 6 weeks

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tobacco product administration and assessment

Trial Overview

The study examines how different flavors of electronic cigarettes like menthol affect tobacco use habits, exposure to harmful substances, and potential for abuse among participants.

How Is the Trial Designed?

Group I: Unflavored Experimental Treatment 1 Intervention

Unflavored - where only unflavored liquid is available for electronic nicotine delivery systems

Group II: Tobacco Experimental Treatment 1 Intervention

Tobacco - where only tobacco flavored liquid is available for electronic nicotine delivery systems

Group III: Menthol+Tobacco Active Control 1 Intervention

Menthol+Tobacco - where both menthol and tobacco flavored liquids for electronic nicotine delivery systems are available to choose from

Who Is Running the Clinical Trial?

Virginia Commonwealth University

Lead Sponsor

Trials

732

Recruited

22,900,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

Many electronic nicotine delivery systems (ENDS) contain varying amounts of nicotine that do not match the concentrations labeled on the cartridges, indicating a lack of consistency and reliability in these products.

The presence of chemicals like propylene glycol and glycerol in ENDS raises safety concerns, as limited information is available about the actual contents, which could affect both recreational users and those attempting to quit smoking.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective. Cheah, NP., Chong, NW., Tan, J., et al.[2022]

A study involving in-depth interviews with 13 adult ENDS users revealed that modifications to devices, such as coils and e-liquids, are commonly made to enhance nicotine delivery, flavor, and vapor production.

Despite a reported decline in modifications due to manufacturer changes, hobbyists still engage in extensive modifications, and regulatory actions by the FDA could inadvertently encourage users to revert to more extensive modifications, impacting safety and product toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Users' Modifications to Electronic Nicotine Delivery Systems (ENDS): Interviews with ENDS Enthusiasts. Li, Y., Fairman, RT., Churchill, V., et al.[2020]

In 2018, an estimated 885 cases of liquid nicotine poisoning among children under 5 were treated in U.S. emergency departments, indicating a concerning trend in exposure.

The majority of these poisoning cases (90%) were treated and released, with ingestion being the most common route of exposure (99.4%), highlighting the need for increased public awareness and safety measures regarding liquid nicotine products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery system (ENDS) liquid nicotine exposure in young children presenting to US emergency departments, 2018. Chang, JT., Rostron, BL.[2022]

In a study of 433 patients with rheumatoid arthritis who had inadequate responses to adalimumab or etanercept, 84.4% reported satisfaction with the golimumab injection experience at week 8, compared to only 63.4% satisfaction with their previous treatments.

Patients continuing with golimumab through week 44 experienced significantly less discomfort and pain during injections compared to their prior tumor necrosis factor antagonist medications, indicating a better overall injection experience.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Satisfaction with Subcutaneous Golimumab and its Auto-Injector among Rheumatoid Arthritis Patients with Inadequate Response to Adalimumab or Etanercept. Dehoratius, RJ., Brent, LH., Curtis, JR., et al.[2018]

The FDA has established the Study Endpoints and Label Development (SEALD) group to improve the evaluation of patient-reported outcomes (PROs) in clinical trials, ensuring that drug approvals and promotional claims are based on reliable measures.

The article outlines FDA-recommended methods for defining a 'responder' in PRO measures, which is crucial for determining meaningful changes in patient outcomes and enhancing the precision of clinical trial results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interpreting patient-reported outcome results: US FDA guidance and emerging methods. McLeod, LD., Coon, CD., Martin, SA., et al.[2022]

In a review of 180 products authorized by the European Medicines Agency from 2008 to 2012, patient-reported outcomes (PROs) were used as primary endpoints in 37% of cases, highlighting their significant role in evaluating treatment efficacy.

Despite the presence of PROs in nearly half of the products studied, the overall usage of PROs, clinician-reported outcomes (CROs), and laboratory-reported outcomes (LROs) remained static, indicating a need for improved transparency and reporting practices in regulatory submissions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of patient-reported outcomes and other efficacy endpoints in the drug approval process in Europe (2008-2012). Bansal, D., Bhagat, A., Schifano, F., et al.[2022]

In a study of 1,489 adult ENDS users, sweet flavors were the most popular, making up 76.2% of the flavors used, while menthol/mint and tobacco flavors were significantly less common.

Users of sweet-flavored liquids tended to use lower nicotine concentrations and higher wattages, suggesting that flavor choice influences device settings and potentially user behavior, which has important implications for regulatory policies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device and liquid characteristics used with sweet, menthol/mint, and tobacco ENDS liquid flavors: The population-based VAPER study. Crespi, E., Hardesty, JJ., Nian, Q., et al.[2023]

A study of 1549 youth aged 13-18 revealed that fruit flavors are the most popular among e-cigarette users, significantly influencing their choice to try e-cigarettes as their first tobacco product.

Youth who preferred fruit flavors were twice as likely to have tried e-cigarettes first, while those who preferred menthol/mint flavors were less likely, highlighting the strong association between flavor preferences and e-cigarette experimentation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Correlates of youth vaping flavor preferences. Groom, AL., Vu, TT., Kesh, A., et al.[2020]

Between 2012 and 2017, there was a nearly sixfold increase in calls to the British Columbia Poison Centre regarding exposures to electronic nicotine delivery systems (ENDS), primarily due to accidental ingestions in young children, particularly those aged 4 years or less.

Of the 186 unique exposures recorded, 46.8% resulted in reported symptoms, highlighting the need for regulatory measures to reduce children's access to ENDS and improve product safety through better labeling and packaging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarette exposures reported to the British Columbia Drug and Poison Information Centre: an observational case series. Choi, A., Le, M., Rahim, T., et al.[2022]

A study involving 30 college-aged JUUL users found that preferred flavours significantly enhanced user satisfaction, enjoyment, and motivation to use the product compared to a classic tobacco flavour.

Despite both flavour conditions leading to increased nicotine levels, the preferred flavour resulted in a much higher likelihood of continued use, suggesting that restricting flavours could help reduce ENDS appeal among young users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of flavour manipulation on ENDS (JUUL) users' experiences, puffing behaviour and nicotine exposure among US college students. Vargas-Rivera, M., Ebrahimi Kalan, M., Ward-Peterson, M., et al.[2023]

In a study of 4909 adults who were established users of electronic nicotine delivery systems (ENDS), 9.8% reported having chronic obstructive pulmonary disease (COPD), with the highest prevalence (19.9%) among users of tobacco-flavored ENDS.

Tobacco-flavored ENDS were found to have a significantly higher association with self-reported COPD (adjusted odds ratio of 2.05) compared to non-tobacco flavors, suggesting a potential link between tobacco flavor use and respiratory health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association of flavored electronic nicotine delivery system (ENDS) use with self-reported chronic obstructive pulmonary disease (COPD): Results from the Population Assessment of Tobacco and Health (PATH) study, Wave 4. Shi, H., Tavárez, ZQ., Xie, Z., et al.[2021]

Electronic nicotine delivery systems (ENDS), like e-cigarettes, were introduced as a safer alternative for smokers, but their use has expanded to young people and non-smokers, raising concerns about unintended health risks.

The design and power of ENDS devices can significantly affect their safety, with higher power devices potentially being more hazardous, highlighting the need for ongoing research to understand the benefits and risks associated with these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clearing the Haze: What Do We Still Need to Learn about Electronic Nicotine Delivery Systems? Fucito, LM., Malinosky, H., Baldassarri, SR., et al.[2023]

Patient-reported outcome measures are becoming increasingly important in clinical care and research, and their integration with electronic health records (EHRs) can enhance patient-centered care and comparative effectiveness research.

The article proposes a framework for standardizing the collection of patient-reported outcomes within EHRs, which could lead to more consistent and comprehensive data collection for improving patient care and research outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measure once, cut twice--adding patient-reported outcome measures to the electronic health record for comparative effectiveness research. Wu, AW., Kharrazi, H., Boulware, LE., et al.[2022]

Incorporating patient-reported outcomes (PROs) into clinical trials is essential for accurately assessing the benefits of new medical products, such as symptom relief and improved functioning.

Standardizing the measurement of PRO endpoints is crucial for translating these benefits into labeling claims, which can guide physicians and patients in making informed treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The patient-reported outcome (PRO) consortium: filling measurement gaps for PRO end points to support labeling claims. Coons, SJ., Kothari, S., Monz, BU., et al.[2022]

Citations

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sciencedirect.com

sciencedirect.com/science/article/abs/pii/S0167629625000487

The effect of e-cigarette flavor bans on tobacco use

We find robust evidence that the adoption of an ENDS flavor restriction reduces short-run frequent and everyday ENDS use among youths by approximately two-to- ...

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pmc.ncbi.nlm.nih.gov

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Persons regularly using menthol-flavored ENDS were no more likely to quit smoking than those regularly using tobacco-flavored ENDS. Three studies used the US ...

3.

jamanetwork.com

jamanetwork.com/journals/jama-health-forum/fullarticle/2828404

Flavored E-Cigarette Sales Restrictions and Young Adult ...

These findings suggest that restricting flavored ENDS sales is associated with reduced vaping but increased cigarette smoking among young adults.

4.

fdli.org

fdli.org/2025/05/what-happens-in-the-real-world-when-flavors-are-banned-in-nicotine-products/

What Happens in the Real World When Flavors ...

But there is real-world evidence suggesting that flavor and other nicotine bans may have unintended consequences—most notably, increasing ...

5.

tobaccocontrol.bmj.com

tobaccocontrol.bmj.com/content/31/Suppl_3/s176

Impact of the FDA flavour enforcement policy on ...

Our results showed that the nicotine use in e-cigarettes is one of the major reasons for continued e-cigarette use after the FDA flavour enforcement policy, as ...

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fda.gov

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E-Cigarettes, Vapes, and other Electronic Nicotine Delivery ...

There are no safe tobacco products, including ENDS. In addition to exposing people to risks of tobacco-related disease and death, FDA has ...

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tobaccocontrol.bmj.com

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Risk and safety profile of electronic nicotine delivery systems ...

We found high-level evidence that ENDS exposes users to toxic substances; increases the risk of respiratory disease; leads to nicotine dependence; causes ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9590402/

Pulmonary effects of e-liquid flavors: a systematic review

The mint/menthol (10 articles) was the most frequently reported to demonstrate harmful effects, followed by cinnamon flavor (9 articles) and strawberry (5 ...

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who.int

who.int/news-room/questions-and-answers/item/tobacco-e-cigarettes

Tobacco: E-cigarettes

Both tobacco products and ENDS pose risks to health. The safest approach is not to use either. The levels of risk associated with using ENDS or tobacco ...

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8683991/

Association between electronic nicotine delivery systems ...

Product modifications or use of flavored e-liquids increased likelihood of symptoms. •. Altering ENDS products or using flavors may increase risk. Keywords: ...