E-Cigarette Flavors for Vaping-Related Respiratory Symptoms

(CRoFT Trial)

Overseen By Maciej Goniewicz, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Roswell Park Cancer Institute

Must not be taking: Aspirin/NSAID

Disqualifiers: Asthma, COPD, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines how switching e-cigarette users from banned flavors like fruit and candy to either tobacco-flavored vapes or tobacco-free nicotine pouches affects respiratory symptoms. Participants will either continue using their current flavored vape, switch to a tobacco flavor, or use nicotine pouches designed to help them stop vaping for 90 days. It suits those who have used flavored e-cigarettes daily for the past six months and do not plan to quit vaping soon. As an unphased trial, this study allows participants to contribute to important research on vaping and respiratory health.

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

The trial protocol does not specify if you need to stop taking your current medications. However, if you have health conditions or are on therapies that affect immune responses, you may be excluded from the trial.

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

Research shows that using e-cigarettes, even with different flavors, carries risks. Some studies have found that certain flavorings in e-cigarettes can damage the lungs. For example, a chemical called diacetyl, found in some flavors, links to serious lung diseases. The U.S. Surgeon General and other health organizations warn that vaping can harm the lungs and may lead to conditions like asthma. Although vaping is often seen as less harmful than smoking regular cigarettes, it still poses health risks, especially to the lungs.

For those considering "tobacco-free" nicotine pouches, it's important to note that these are relatively new. They might seem safer because they don't involve inhaling vapor, but they still contain nicotine, which is addictive. The long-term safety of these pouches remains unclear.

In summary, while both options have risks, switching from flavored vaping to tobacco-flavored vaping or using nicotine pouches might lower exposure to some harmful chemicals. However, it's crucial to consider the potential health impacts. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different e-cigarette flavors and tobacco-free nicotine pouches might impact vaping-related respiratory symptoms. Unlike traditional cessation methods like nicotine replacement therapies and counseling, this trial evaluates the role of flavor in managing symptoms, offering a novel angle on harm reduction. By examining the effects of flavored e-cigarettes, a new tobacco flavor, and complete vaping abstinence with the use of tobacco-free nicotine pouches, the trial could reveal how flavor influences respiratory health and help tailor more effective strategies for those looking to quit or reduce vaping.

What evidence suggests that this trial's treatments could be effective for vaping-related respiratory symptoms?

Research has shown that e-cigarettes are generally considered less harmful than regular cigarettes, with some studies suggesting they are at least 95% safer. However, users often report more breathing problems than non-users. Some e-liquid flavors contain chemicals that might harm the lungs, even if safe to eat. This trial will compare different approaches: one group will continue using their own brand of flavored e-cigarettes, another will use a provided tobacco flavor, and a third group will abstain from vaping and use tobacco-free nicotine pouches instead. E-cigarettes have been found to help people quit smoking more effectively when combined with counseling. While there is limited data on the effects of tobacco-free nicotine pouches on breathing, they are used to reduce harm from tobacco. ^{1 3 6 7 8}

Who Is on the Research Team?

Maciej Goniewicz, PhD

Principal Investigator

Roswell Park

Are You a Good Fit for This Trial?

This trial is for adults who've been using electronic nicotine delivery systems (ENDS) with banned flavors like fruit or candy daily for the past 6 months and don't plan to quit soon. They shouldn't have smoked tobacco or used smokeless tobacco in the last 6 months, must be free of respiratory illness for a month before joining, and can't have health conditions affecting immune responses.

Inclusion Criteria

No smoking tobacco or using smokeless tobacco for the past 6 months

I do not plan to quit vaping or stop using flavored products in the next 90 days.

Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure

Exclusion Criteria

I have conditions or take medications that might affect my immune system.

History of serious side effects from nicotine or from any nicotine replacement therapies

Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants switch from banned flavors to a non-banned flavor (tobacco) or 'tobacco free' nicotine pouches for 90 days

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• E-cigarette Flavor
• Tobacco Free Nicotine Pouch

Trial Overview The study compares respiratory symptoms in people switching from banned flavored e-cigarettes to a non-banned flavor (tobacco) or 'tobacco free' nicotine pouches. It's randomized, meaning participants are put into groups by chance, and open-label so everyone knows which intervention they receive.

How Is the Trial Designed?

Group I: Use Provided Tobacco Flavor Experimental Treatment 1 Intervention

Participants will use a new assigned flavor for 90 days

Group II: Use Own Brand of Flavored Product Experimental Treatment 1 Intervention

Participants will use their current flavor of e cigarettes for 90 days

Group III: Vaping Abstinence - use "Tobacco Free" Nicotine Pouches Active Control 1 Intervention

Participants will be asked to stop vaping for 90 days and instead only use the provided 'tobacco free' nicotine pouches.

E-cigarette Flavor is already approved in United States, European Union for the following indications:

Approved in United States as E-liquids for:

• Nicotine replacement therapy for smoking cessation

Approved in European Union as Electronic Nicotine Delivery Systems (ENDS) for:

• Nicotine replacement therapy for smoking cessation

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

University of Rochester

Collaborator

Trials

883

Recruited

555,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Published Research Related to This Trial

In a study of 18,079 adults aged 18-44, e-cigarette users reported higher rates of respiratory symptoms, with 45% of occasional users experiencing issues like cough and shortness of breath, compared to 28% overall.

The odds of reporting respiratory symptoms increased by 49% for those who used e-cigarettes some days and by 29% for former users, indicating that e-cigarettes may not be a safe alternative to traditional cigarettes for respiratory health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. Varella, MH., Andrade, OA., Shaffer, SM., et al.[2023]

A study of five brands of electronic nicotine delivery systems (ENDS) revealed significant design flaws, including leaking cartridges and difficulty in handling without exposure to nicotine, raising safety concerns for users.

The labeling and instructions for ENDS were often inadequate and misleading, lacking essential safety information and proper disposal guidelines, suggesting a need for regulatory review before these products remain on the market.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: is there a need for regulation? Trtchounian, A., Talbot, P.[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]

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]

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 total of 92 overheating, fire, or explosion (OH/F/EXP) events related to electronic nicotine delivery systems (ENDS) were identified in the USA, with 49% resulting in injuries to 47 individuals and 73% causing property damage beyond the product itself.

The report highlights the need for improved surveillance and risk mitigation strategies, as some incidents have led to severe injuries and significant property damage, indicating that the causes and scope of these events are not fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: overheating, fires and explosions. Rudy, SF., Durmowicz, EL.[2022]

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]

Exposure to flavored e-cigarette aerosols (ENDS) led to decreased cell viability and metabolic activity in human bronchial epithelial cells, along with increased release of inflammatory cytokines, indicating potential inhalation toxicity.

Among the tested products, a strawberry-flavored ENDS was found to be the most cytotoxic, suggesting that flavoring and device characteristics significantly influence the toxicity of e-cigarette aerosols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Leigh, NJ., Lawton, RI., Hershberger, PA., et al.[2023]

Five out of seven common e-liquid flavoring chemicals were found to be cytotoxic to airway epithelial cells at concentrations typically found in e-liquids, indicating potential respiratory risks.

The flavoring chemical 2,5-dimethylpyrazine not only caused cell death but also disrupted the airway epithelial cells' ability to respond to important signaling molecules, potentially affecting airway surface liquid balance and function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Airway epithelial cell exposure to distinct e-cigarette liquid flavorings reveals toxicity thresholds and activation of CFTR by the chocolate flavoring 2,5-dimethypyrazine. Sherwood, CL., Boitano, S.[2018]

In a study of 1,432 current electronic nicotine delivery systems (ENDS) users, those who used refillable devices and flavored e-liquids reported higher rates of clinical symptoms, including EVALI-like symptoms such as cough and nausea.

Younger users, particularly those who identified as Hispanic or were current smokers, were more likely to experience EVALI-like symptoms, indicating a potential risk factor associated with specific demographics and usage patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between electronic nicotine delivery systems (ENDS) device and E-liquid alterations and flavor use with clinical and EVALI-like symptoms. Hart, JL., Payne, TJ., Groom, A., et al.[2022]

A review of 38 studies found that flavored e-liquids, particularly those with cinnamon, strawberry, and menthol, can have significant adverse effects on the respiratory system, including increased inflammation and cytotoxicity.

While some flavoring compounds like diacetyl and cinnamaldehyde are known to be toxic when inhaled, the safety profiles of many other e-liquid flavors remain unclear, highlighting the need for more systematic research to assess their risks to public health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary effects of e-liquid flavors: a systematic review. Effah, F., Taiwo, B., Baines, D., et al.[2022]

Nicotine pouches, a new product category, are being marketed with minimal research and regulatory oversight, highlighting significant gaps in understanding their potential harms and benefits.

The commentary suggests a comprehensive assessment approach to inform regulatory policies, aiming to enhance public health outcomes while reducing unintended negative effects associated with nicotine pouch use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? Patwardhan, S., Fagerström, K.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12516984/

Health impacts of electronic nicotine delivery systems Our analysis did not reveal significant damage to pulmonary function test values; however, studies on respiratory outcomes associated with ENDS ...

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

Pulmonary effects of e-liquid flavors: a systematic review A review commissioned by Public Health England of available evidence suggested that ECs are at least 95% less harmful to health than tobacco smoking (McNeill et ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation The addition of e-cigarettes to standard smoking-cessation counseling resulted in greater abstinence from tobacco use among smokers than smoking ...

4. nature.com nature.com/articles/s41598-024-80221-8

Respiratory symptoms among e-cigarette users without an ... Vapers reported a significantly higher frequency of respiratory symptoms over P30D; however, the difference in RSES score was 0.18, which is ...

5. cdc.gov cdc.gov/tobacco/e-cigarettes/health-effects.html

Health Effects of Vaping | Smoking and Tobacco Use Flavorings such as diacetyl, a chemical linked to a serious lung disease. Some flavorings used in e-cigarettes may be safe to eat but not to ...

6. lung.org lung.org/quit-smoking/e-cigarettes-vaping/impact-of-e-cigarettes-on-lung

Health Risks of E-Cigarettes and Vaping It can cause acute lung injury and COPD and may cause asthma and lung cancer.4; Both the U.S. Surgeon General and the National Academies of ...

7. fda.gov fda.gov/tobacco-products/products-ingredients-components/e-cigarettes-vapes-and-other-electronic-nicotine-delivery-systems-ends

E-Cigarettes, Vapes, and other Electronic Nicotine Delivery ... Get an overview of FDA regulation of e-cigarettes, vapes, and other electronic nicotine delivery systems. You can also find statistics about ...

8. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/21162-vaping

Vaping (E-Cigarettes): What It Is, Side Effects & Dangers Vaping isn't safe and can cause health problems, including life-threatening lung injuries.