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

163 Participants Needed

Trial Summary

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.

What data supports the idea that E-Cigarette Flavors for Vaping-Related Respiratory Symptoms is an effective treatment?

The available research does not provide data supporting the idea that E-Cigarette Flavors for Vaping-Related Respiratory Symptoms is an effective treatment. Instead, the studies focus on the safety, regulatory challenges, and potential health risks associated with using flavored electronic nicotine delivery systems (ENDS). For example, one study found a significant association between ENDS use and chronic obstructive pulmonary disease (COPD), suggesting potential health risks rather than benefits. Therefore, there is no evidence from the provided research that supports the effectiveness of this treatment for respiratory symptoms. ^{1 2 3 4 5}

What safety data exists for e-cigarette flavors and related products?

Existing safety data for e-cigarette flavors and related products, such as ENDS and nicotine pouches, highlight several concerns. Studies have noted the potential for overheating, fires, and explosions with ENDS devices. There are also reports of acute adverse events from liquid nicotine exposure, particularly in young children. Additionally, there is a lack of comprehensive research and regulatory oversight for nicotine pouches, indicating a need for further study to assess their harm and benefit potential. ^{1 3 6 7 8}

Is the treatment E-cigarette Flavor, Tobacco Free Nicotine Pouch a promising treatment for vaping-related respiratory symptoms?

Based on the research articles, e-cigarette flavors, including tobacco-free nicotine pouches, are not promising for treating vaping-related respiratory symptoms. Instead, they are associated with potential respiratory issues and harmful effects on the lungs. ^{2 9 10 11 12}

What is the purpose of this trial?

This is a randomized, parallel-group open-label trial to evaluate respiratory symptoms in ENDS users switching from banned flavors to a non-banned flavor (tobacco) or 'tobacco free' nicotine pouches.

Research Team

Maciej Goniewicz, PhD

Principal Investigator

Roswell Park

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: regulatory and safety challenges: Singapore perspective. [2022]

2. Greece 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Device and liquid characteristics used with sweet, menthol/mint, and tobacco ENDS liquid flavors: The population-based VAPER study. [2023]

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

Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). [2023]

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

Electronic nicotine delivery systems: is there a need for regulation? [2022]

6. England pubmed.ncbi.nlm.nih.gov

The New Nicotine Pouch Category: A Tobacco Harm Reduction Tool? [2023]

7. England pubmed.ncbi.nlm.nih.gov

Electronic nicotine delivery systems: overheating, fires and explosions. [2022]

8. England pubmed.ncbi.nlm.nih.gov

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

9. United States 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. [2022]

10. England 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. [2018]

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

E-cigarette use and respiratory symptoms in residents of the United States: A BRFSS report. [2023]

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

Pulmonary effects of e-liquid flavors: a systematic review. [2022]