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Completed

NCT Number: NCT05205382

Assessing the Effect of Nicotine Reduction on ENDS User's Addiction and Exposures

The rapid increase of electronic nicotine delivery systems (ENDS) use by young people in the US and their potential to harm health, cause addiction, and serve as a risk for cigarette smoking or dual-use is alarming. The epidemic of ENDS use among young people in the US has been associated with the rise in popularity of ENDS products that are very efficient in delivering high doses of nicotine to users. Therefore, the investigators propose to study the effects of nicotine reduction (NR) on young ENDS users as a potential regulatory strategy to reduce the addictiveness and use of ENDS. The proposed studies are directly responsive to research priories identified by the FDA and specified in this RFA under Addiction; studying the "Impact of changes in tobacco product characteristics (e.g. nicotine formulation) on dependence". This project aims to provide an overview of this project's rationale significance divided into 1) scientific rationale and regulatory implications; 2) the need to respond to the rising trend of ENDS use among young people in the US; 3) the importance of reducing the addictiveness of ENDS; 4) the strength of our clinical and analytical lab approach for regulatory purposes; and 5) the strengths and weaknesses in the rigor of prior research about NR for ENDS.

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Key information

Conditions

Electronic Cigarette Use Behavior Smoking Vaping

Age range

21 year–35 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Florida International University

Miami, Florida, 33199, United States

About this study

The use of electronic nicotine delivery systems (ENDS or e-cigarettes) has reached epidemic levels among young people in the United States (US). ENDS emit toxic substances, including nicotine that irreversibly affects the developing brain and leads to dependence and increased risk of cigarette smoking initiation. Evidence indicates that young people using ENDS are likely to accelerate use and become nicotine dependent. Some of the most popular ENDS among youth (e.g. JUUL with 5% nicotine liquid) deliver in one cartridge a nicotine dose equal to an entire pack of cigarettes, and many users are unaware of this substantial exposure and the related risk of addiction. On the other hand, nicotine reduction (NR) has been considered by the US Food and Drug Administration (FDA) as an important strategy to limit the addictiveness and use of tobacco products.

Now that the FDA regulates ENDS under the "deeming rule", such a strategy can be considered for these emerging tobacco products. However, the investigators still lack evidence on the expected effects of a range of NR levels on ENDS users at different stages of use trajectory. Using clinical and analytical lab methods, the investigators plan to compare among 5% nicotine ENDS users the effect of partial (3%/2.4%) or total (nicotine-free, 0%) NR on users' dependence, satisfaction, clinical (e.g. BP, oximetry, lung functions, symptoms), puffing behavior, and exposure to toxicants. The investigators will recruit current ENDS users (n=120; 21-35 yrs), for a 2X2 within subject crossover lab study. The nicotine conditions (5%, 3%/2.4%) or (0%,5%) x 2 times (pre-post) are the within-subject factors.

Therefore, the study is divided into 2 parts, whereby the first part will be 2x2 comparing JUUL/NJOY 5% and 3%/2.4% to test the effects of partial nicotine reduction, and the second part will be using the NIDA Standardized Research Electronic Cigarette (SREC) for Clinical Research 5% and 0% (placebo), to test the effect of the total reduction using the same pods and juices from the same manufacturer.

The investigators hypothesize that NR will be associated with less satisfaction, withdrawal suppression, and intention to use and that such an effect will be more pronounced in total compared to partial NR and among high compared to low-dependency users. The proposed studies aim to answer 3 main regulatory questions: 1) is NR a promising regulatory option to reduce ENDS addictiveness and use; 2) what is the effect of partial vs. total NR on compensatory puffing and exposure to nicotine and respiratory toxicants, and 3) what is the effect of NR on ENDS users at different stages of their use. Combined, these studies will give direct and standardized evidence on the potential of NR regulations to limit the addictiveness and use of ENDS, and to help predict any potential side effects of NR on ENDS users' exposure to harmful toxicants.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Generally healthy individuals (determined by physical examination).
  • Age of 21-35 years.
  • Is willing to provide informed consent.
  • Is willing to attend the lab as required by the study protocol.
  • Electronic cigarette users (defined as using electronic cigarette either daily or occasionally in the past 30 days)
  • Have abstained from electronic cigarette use for 12 hours prior to each session

Exclusion criteria

  • Report smoking cigarettes regularly (> 5 cigarettes/month in the past year).
  • Report regular use of any other tobacco/nicotine product (e.g.,hookah, pipes, cigars) in the past year.
  • Women who are breast-feeding or test positive for pregnancy (by urinalysis at screening).
  • Individuals with self-reported history of chronic disease or current psychiatric conditions.
  • Individuals with history of or active cardiovascular disease, low or high blood pressure, seizures, and regular use of prescription medications (other than vitamins or birth control).
  • Individuals that report current THC (marijuana) smoking/vaping.
  • Individuals that report the use of non-commercial (i.e., street) e-cigarette liquid or products
  • Individuals that report current EVALI or COVID-19 related symptoms (i.e., cough, shortness of breath, chest pain, nausea, vomiting, abdominal pain, diarrhea, fever, chills, or weight loss)
  • Individuals that have or have been exposed to COVID-19 in the last 14 days.

Treatment and study plan

5% nicotine (Partial Nicotine Reduction)

Other

Partial Nicotine Reduction: Effects of e-cigarette pods (JUUL/NJOY) with 5% nicotine concentration nicotine concentration

3% or 2.4% nicotine (Partial Nicotine Reduction)

Other

Partial Nicotine Reduction: Effects of e-cigarette pods (JUUL/NJOY) with 3% or 2.4% nicotine concentration

5% nicotine (Total Nicotine Reduction)

Other

Total Nicotine Reduction: Effects of e-cigarette pods (SREC) with 5% nicotine concentration

0% nicotine (Total Nicotine Reduction)

Other

Total Nicotine Reduction: Effects of e-cigarette pods (SREC) with 0% nicotine concentration nicotine concentration

Primary outcomes

  1. Plasma Nicotine Boost

    Time frame: During the 2 participant visits, blood was taken 2 times in each session: before and after approximately 60 minutes ad lib use.

    Change in plasma nicotine level. The plasma nicotine boost was calculated by subtracting the preplasma nicotine value from the postplasma value.

Secondary outcomes

  1. Puff Topography (Total Puffing Time)

    Time frame: During participants' 2 study visits. Puffing behavior is continuously measured during each electronic cigarette use session (an approximately 60 minutes ad lib use period)

    Measurement of puffing behavior in total puffing time

  2. Puff Topography (Average Puff Duration)

    Time frame: During participants' 2 study visits. Puffing behavior is continuously measured during each electronic cigarette use session (an approximately 60 minutes ad lib use period)

    Measurement of puffing behavior in average puffing duration

  3. Puff Topography (Puff Number)

    Time frame: During participants' 2 study visits. Puffing behavior is continuously measured during each electronic cigarette use session (an approximately 60 minutes ad lib use period)

    Measurement of puffing behavior; mean of the number of puffs taken during the ad-libitum smoking session

  4. Puff Topography (Inhaled Volume)

    Time frame: During participants' 2 study visits. Puffing behavior is continuously measured during each electronic cigarette use session (an approximately 60 minutes ad lib use period)

    Measurement of puffing behavior; mean volume of puffs inhaled during the ad-libitum smoking session

  5. Toxicants (Carcinogenic and Probably or Possibly Carcinogenic) Exposure

    Time frame: During the 2 participant visits for both trials (partial and total). Toxicant exposure was measured after an approximately 60 minutes ad lib electronic cigarette use period.

    This aim elucidates how compensatory puffing behavior in response to NR affects exposure to pulmonary toxicants. The analytical assessments were conducted at the AUB Aerosol Research Laboratory (ARL) using the Aerosol Lab Vaping Instrument (ALVIN). The ALVIN is programmed to playback participants' puffing behavior recorded during their two sessions (for both partial and total nicotine reduction studies) to generate and sample the e-cigarette aerosol for analysis. The ARL is equipped with gas chromatographs with a flame ionization detector and a mass spectrometer (GC-FID, GC-MS), as well as and High-performance liquid chromatography Mass Spectrometry (HPLC-MS) for aldehydes analysis. ARL optimized analytical methods have been used in several NIH-funded studies of ENDS nicotine and aldehydes emissions.

  6. TPM (Total Particular Matter) Exposure

    Time frame: During the 2 participant visits for both trials (partial and total). Total Particular Matter exposure was measured after an approximately 60 minutes ad lib electronic cigarette use period.

    This aim elucidates how compensatory puffing behavior in response to NR affects exposure to pulmonary toxicants. The analytical assessments were conducted at the AUB Aerosol Research Laboratory (ARL) using the Aerosol Lab Vaping Instrument (ALVIN). The ALVIN is programmed to playback participants' puffing behavior recorded during their two sessions (for both partial and total nicotine reduction studies) to generate and sample the e-cigarette aerosol for analysis. The ARL is equipped with gas chromatographs with a flame ionization detector and a mass spectrometer (GC-FID, GC-MS), as well as and High-performance liquid chromatography Mass Spectrometry (HPLC-MS) for aldehydes analysis. ARL optimized analytical methods have been used in several NIH-funded studies of ENDS nicotine and aldehydes emissions.

  7. Lung Function Tests (LFTs) Change

    Time frame: During participants' 2 study visits. Lung function tests will be measured 2 times in each electronic cigarette use session: before and after an approximately 60 minutes ad lib use period

    LFTs (i.e., lung volume testing, airway resistance, specific airway conductance) will be measured before and immediately after ENDS use. According to 2019 American Thoracic Society and European Respiratory Society recommendation simple spirometry (e.g., change in FVC and FEV1) will be performed. Note: This outcome is not involved in multiple assessments since all the values will appear on the spirometry at the same time.

  8. Lung Function Tests (LFTs) (% Predicted Change)

    Time frame: During participants' 2 study visits. Lung function tests will be measured 2 times in each electronic cigarette use session: before and after an approximately 60 minutes ad lib use period

    LFTs (i.e., lung volume testing, airway resistance, specific airway conductance) will be measured before and immediately after ENDS use. According to 2019 American Thoracic Society and European Respiratory Society recommendation simple spirometry (e.g., % predicted value pred (FVC), FEV1 % pred FEV1/FVC, % pred) will be performed. Note: This outcome is not involved in multiple assessments since all the values will appear on the spirometry at the same time.

  9. Minnesota Nicotine Withdrawal Scale (MNWS)

    Time frame: During participants' 2 study visits. Questionnaire will be administered 2 times in each electronic cigarette use session: before and after an approximately 60 minutes ad lib use period

    Nicotine withdrawal symptoms were measured using the Minnesota Nicotine Withdrawal Scale (MNWS) before and after each vaping session. MNWS evaluates 11 withdrawal-related symptoms, including depressed mood, irritability, restlessness, hunger, and difficulty concentrating, using scale from "0" (not at all) to "100" (extremely). For each session and condition, change scores were calculated by subtracting pre-session from post-session scores for each individual item

  10. Tiffany-Drobes Questionnaire of Smoking Urges (QSU)

    Time frame: During participants' 2 study visits. Questionnaire will be administered 2 times in each electronic cigarette use session: before and after an approximately 60 minutes ad lib use period

    The Tiffany-Drobes Questionnaire of Smoking Urges-Brief (QSU-Brief) is a 10-item self-report measure of cigarette craving and urge to smoke. It consists of two subscales representing distinct dimensions of craving:

    Factor 1 (Desire and Intention to Smoke): assesses desire, intention, and anticipation of pleasure associated with smoking.

    Factor 2 (Anticipation of Relief from Negative Affect and Withdrawal): assesses expectations that smoking will relieve withdrawal symptoms or negative affect.

    Each item is rated on a 7-point Likert scale ranging from 1 = strongly disagree to 7 = strongly agree. Subscale scores were calculated by averaging the items within each factor. Higher scores on either factor indicate greater smoking urge or craving, representing a worse outcome, whereas lower scores indicate lower craving or urge to smoke, representing a better outcome. Pre- to post-session change scores were calculated as pre-session score minus post-session score for each factor.

  11. Duke Sensory Questionnaire (DSQ)

    Time frame: During participants' 2 study visits. Questionnaire will be administered after each of the 2 electronic cigarette use sessions. Each session is approximately 60 minutes ad lib use period

    This scale will assess participants sensory experience of the inhaled product. The scale has nine items. All items will be scored on a 7-point Likert scale anchored at the extremes (1= not at all; 7=extremely).

  12. Modified Cigarette Evaluation Questionnaire (mCEQ)

    Time frame: During participants' 2 study visits. Questionnaire will be administered after each of the 2 electronic cigarette use sessions. Each session is approximately 60 minutes ad lib use period

    Modified Cigarette Evaluation Questionnaire (mCEQ) is used to assess subjective effects associated with ENDS use. The 11-item questionnaire evaluates satisfaction, psychological reward, enjoyment of respiratory tract sensations, craving reduction and aversion. Individual item scores were reported (not subscales). Each item was rated using 7-point Likert scale; 1 = not at all to 7 = extremely. For all items, higher scores indicate greater endorsement of the measured subjective experience, while lower scores indicate less endorsement of that experience. The interpretation depends on the construct being measured:

    For items assessing satisfaction, enjoyment, psychological reward, sensory experiences, and craving reduction, higher scores indicate greater product reinforcement or abuse liability. For items assessing aversion, higher scores indicate greater unpleasant effects or product aversiveness.

  13. Visual Analogue Scale (VAS)

    Time frame: During participants' 2 study visits. Questionnaire will be administered after each of the 2 electronic cigarette use sessions. Each session is approximately 60 minutes ad lib use period

    This scale contains 10-item questions to assess users' pleasure and enjoyment using the validated Visual Analog Scale (VAS) post ENDS use sessions. The scale includes items to assess user's desire, pleasure, satisfaction, future use, and other information rated on an analog scale (0 not at all to 100 extremely).

Other outcomes

  1. Heart Rate

    Time frame: During participants' 2 study visits. Heat rate will be measured from baseline and subsequently every 10 minutes until end of vaping session.

    Change in heart rate, measured in beats per minute (bpm).

  2. Blood Pressure (Systolic)

    Time frame: During participants' 2 study visits. Blood pressure will be measured from baseline and subsequently every 10 minutes until end of vaping session.

    Change in systolic blood pressure, measured in mm/hg.

  3. Blood Pressure (Diastolic)

    Time frame: During participants' 2 study visits. Blood pressure will be measured from baseline and subsequently every 10 minutes until end of vaping session.

    Change in diastolic blood pressure, measured in mm/hg.

Sponsors and collaborators

Lead sponsor

Florida International University

Other

Registry information

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jan 25, 2022
Registry last updated
Aug 13, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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