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Completed

NCT Number: NCT05430334

Assess the Influence of Nicotine Flux and Nicotine Form on Subjective Effects Related to Dependency

Electronic nicotine delivery systems (ENDS) heat and vaporize a nicotine-containing liquid to produce an aerosol that can deliver nicotine to the blood and the brain. ENDS use has increased rapidly in the last decade, especially among youth: over 20% of US high school students are current ENDS users, and there is evidence of nicotine dependence in this population. Federal legislation has been proposed that would restrict ENDS liquid nicotine concentration to make ENDS "significantly less addictive and appealing to youth." However, these and other efforts to curb addiction by limiting nicotine liquid concentration are unlikely to succeed because nicotine emissions from ENDS depend on multiple variables. To achieve the intended public health aims, regulations targeting addiction must focus on nicotine delivery, not nicotine concentration. While nicotine delivery cannot be regulated directly, the rate at which an ENDS emits nicotine, the "nicotine flux", can be regulated and, importantly, predicted based on a few device design and operating variables. However, to date there is no empirical evidence demonstrating the relationship between flux and delivery, nor between flux and the subjective effects that support nicotine dependence. Closing this gap is essential for providing an effective framework for regulating ENDS. At the American University of Beirut, the investigators will assess the relationship between nicotine flux, form, and subjective effects. Participants will use ENDS devices with varying nicotine fluxes and forms. Dependency measures, such as urge to smoke, craving, and abstinence, will be assessed. The outcome will indicate the degree to which nicotine flux/form influence subjective effects related to dependency, puffing intensity, and exposure to toxicants. In summary, this project will provide the empirical evidence needed for public health agencies to use nicotine flux as an encompassing and convenient construct to regulate nicotine delivery from ENDS.

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Key information

Conditions

Nicotine Vaping Behavior Chemically-Induced Disorders Mental Disorders Nicotine Addiction Nicotine Dependence Smoking Substance-Related Disorders Tobacco Use Disorder Vaping

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

American University of Beirut

Beirut, 11-0236, Lebanon

About this study

Assess the influence of nicotine flux and nicotine form on subjective effects. At AUB, the investigators will assess subjective effects (e.g. product liking, nicotine craving) and puffing topography for 130 participants who will undergo 5 ENDS use sessions (combinations 1-5) consisting of 2 bouts (10 puffs + 60min ad libitum) with 2 fluxes (15 and 35μg/s) x 2 forms (protonated, freebase) and a 0 nicotine condition. In addition, the investigators will use a state-of-the-art device to sample in situ a fraction of the aerosol generated during each puff to verify actual nicotine flux and form, and measure exposure to pulmonary toxicants (carbonyls). The investigators hypothesize that increasing nicotine flux and protonated nicotine will result in greater reductions of nicotine craving, and lower puffing intensity and carbonyl exposure. 10 of the participants that completed AIM 2 will be asked to attend our lab at AUB for one additional visit, where they will be assigned either a high flow or low flow ENDS. During the visit, participants will undertake three smoking bouts consisting of 10 puffs each, where they will be presented with alternating puffs of the assigned device in which a specific ENDS design variable is systematically varied between puffs. Puff topography, inhalation behavior, and subjective effects related to sensory feedback will be recorded. We hypothesize that power and liquid composition variations will result in immediate and reversible changes in puffing/inhalation behavior.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

  • Must be healthy and above 18 years of age
  • Must be willing to provide informed consent, attend the lab, and abstain from tobacco/nicotine as required (participants will be instructed to abstain from nicotine/tobacco and/or ENDS use for ≥12h)
  • A dual ENDS and tobacco user who reports daily use of ENDS (≥ 3 mg/ml nicotine) or cigarettes (any frequency) AND someday use (≥ 3 days/week) of ENDS (≥ 3 mg/ml nicotine) or cigarettes (any frequency) for the past 3 months or longer

Exclusion criteria

  • History of chronic disease or an uncontrolled psychiatric condition
  • History of or active cardiovascular disease, low/high blood pressure, seizures, regular use of a prescription medication (except vitamins/birth control)
  • Past month use of cocaine, opioids, benzodiazepines, or methamphetamines
  • Individuals who report using marijuana >15/30 days
  • Women will be excluded if they are breast-feeding or pregnant
  • Participants intending to quit tobacco/nicotine use in the next 30 days and referred to cessation treatment

Treatment and study plan

e-liquid 1

Combination Product

30/70 propylene glycol/vegetable glycerin ratio with nicotine concentration 4mg/ml protonated

e-liquid 2

Combination Product

30/70 PG/VG ratio with nicotine concentration 10mg/ml protonated

e-liquid 3

Combination Product

30/70 PG/VG ratio with nicotine concentration 4mg/ml free base

e-liquid 4

Combination Product

30/70 PG/VG ratio with nicotine concentration 10mg/ml freebase

e-liquid 5

Combination Product

30/70 PG/VG ratio with nicotine concentration 0mg/ml (placebo)

e-liquid 6

Combination Product

30/70 PG/VG ratio with nicotine concentration 0mg/ml

e-liquid 7 and e-liquid 8

Combination Product

e-liquid 7: 30/70 PG/VG ratio with nicotine concentration 4mg/ml protonated e-liquid 8: 30/70 PG/VG ratio with nicotine concentration 8mg/ml protonated

e-liquid 9 and e-liquid 10

Combination Product

e-liquid 9: 30/70 PG/VG ratio with nicotine concentration 4mg/ml protonated e-liquid 10: 70/30 PG/VG ratio with nicotine concentration 4mg/ml protonated

Primary outcomes

  1. Subjective Effects - Strong Flavor (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Strong flavor will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating a stronger perceived flavor.

  2. Subjective Effects - Harshness/Irritancy (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Harshness/irritancy will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating harsher/more irritating effects.

  3. Subjective Effects - Throat Hit (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Throat hit will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-10, No sensation - Strongest Imaginable), with higher scores indicating a stronger throat hit.

  4. Subjective Effects - Overall Like: Flavor (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Overall like: flavor will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the flavor was liked more.

  5. Subjective Effects - Overall Like: Harshness (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Overall like: harshness will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the harshness was liked more.

  6. Subjective Effects - Overall Like: Throat Hit (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Overall like: throat hit will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the throat hit was liked more.

  7. Subjective Effects - Overall Like: Warmth (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Overall like: warmth will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) on a subjective scale (0-10, most disliked - most liked), with higher scores indicating the warmth was liked more.

  8. Subjective Effects - Satisfying (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Satisfying will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater satisfaction.

  9. Subjective Effects - Pleasant (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Pleasant will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater pleasantness.

  10. Subjective Effects - Taste Good (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Taste good will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating better taste.

  11. Subjective Effects - Calm (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Calm will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling calmer.

  12. Subjective Effects - Concentrate (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Concentrate will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating better ability to concentrate.

  13. Subjective Effects - Awake (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Awake will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling more awake/alert.

  14. Subjective Effects - Reduce Hunger (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Reduce hunger will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater reduction in hunger.

  15. Subjective Effects - Dizzy (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Dizzy will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating greater dizziness.

  16. Subjective Effects - Feeling Sick (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Feeling sick will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating feeling more sick.

  17. Subjective Effects - Want it Right Now (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Want it right now will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating a stronger immediate desire for the product.

  18. Subjective Effects - Smell (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Smell will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating a stronger perceived smell. This item is drawn from the Electronic Cigarette Specific Effects Questionnaire, a modified/expanded version of the modified Cigarette Evaluation Questionnaire (mCEQ; Cappelleri et al., 2007) developed for ENDS. Participants rate the item on a 0-10 scale immediately following each bout. Item wording: 'Did the e-cig produce a smell?' (0 = not at all, 10 = extremely).

  19. Subjective Effects - Visible Vapor (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Visible vapor will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating more visible vapor.

  20. Subjective Effects - Importance Vapor (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Importance vapor will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating vapor visibility mattered more to the participant. This item is drawn from the Electronic Cigarette Specific Effects Questionnaire, a modified/expanded version of the modified Cigarette Evaluation Questionnaire (mCEQ; Cappelleri et al., 2007) developed for ENDS. Participants rate the item on a 0-10 scale immediately following each bout. Item wording: 'Is the vapor/cloud of the e-cig important to you?' (0 = not at all, 10 = extremely).

  21. Subjective Effects - Puffs Similar (Combinations 1-5)

    Time frame: Post Bout 1: assessed 5 minutes after onset of the directed 10-puff bout (average bout duration ~5 minutes). Post Bout 2: assessed 5 minutes after onset of the 60-minute ad libitum bout.

    Puffs similar will be assessed by the Electronic Cigarette Specific Effects questionnaire and consists of 1 item scored 0 - 10 with 0 being not at all and 10 being extremely, with higher scores indicating the puffs were perceived as more similar to the participant's usual product.

  22. Smoking Urges - Brief Factor 1 (Intention/Desire)

    Time frame: Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).

    Brief Factor 1 (Intention/Desire) will be assessed by the Questionnaire of Smoking Urges-Brief (QSU-Brief; Tiffany & Drobes, 1991; Toll et al., 2006). Factor 1 is the sum of 6 items, each rated on a 0-10 scale (0=strongly disagree, 10=strongly agree), yielding a total score range of 0-60, with higher scores indicating stronger urges.

  23. Smoking Urges - Brief Factor 2 (Relief of Neg. Affect)

    Time frame: Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).

    Brief Factor 2 (Relief of Neg. Affect) will be assessed by the Questionnaire of Smoking Urges-Brief (QSU-Brief; Tiffany & Drobes, 1991; Toll et al., 2006). Factor 2 is the sum of 4 items, each rated on a 0-10 scale (0=strongly disagree, 10=strongly agree), yielding a total score range of 0-40, with higher scores indicating stronger urges.

  24. Withdrawal Symptoms - Minnesota Nicotine Withdrawal Scale (MNWS; Based on Hughes and Hatsukami, 1986)

    Time frame: Assessed before and after the directed bout (Bout 1), and before, midway through, and after the ad libitum bout (Bout 2).

    The Minnesota Nicotine Withdrawal Scale (MNWS; based on Hughes and Hatsukami, 1986 questionnaire) was measured using composite mean of MNWS items (irritability, anxiety, difficulty concentrating, restlessness, hunger/appetite, Impatient, depression, desire for sweets and craving) on a 0-10 scale (Not at all - Extremely), with higher scores indicating greater withdrawal severity.

Secondary outcomes

  1. Puff Duration

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Puff duration combination 1,2,3,4 & 5

  2. Number of Puffs

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Measured topography Total Number of Puffs (puffs).

  3. Puffing Time

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Measured topography Average Puffing time (sec).

  4. Inter Puff Interval

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Measured topography Average Inter Puff Interval (sec).

  5. Flow Rate

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Measured topography Average Flow rate (Liters per minute: LPM).

  6. Mouth-level PM

    Time frame: Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Mouth-level PM (Particulate matter) dose estimated using the REALTIME real-time in-situ sampling device, which collects 5% of the aerosol at the mouthpiece during each puff; values are reported as the total session dose (5% fraction × 20), in mg.

  7. Mouth-level Nicotine

    Time frame: Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout

    Mouth-level nicotine dose estimated using the REALTIME real-time in-situ sampling device, which collects 5% of the aerosol at the mouthpiece during each puff; values are reported as the total session dose (5% fraction × 20), in mg.

  8. Puff Duration - Combination 6,7 & 8

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout

    Measured topography Average Puff Duration (sec) - using Subox mini C. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.

  9. Sensory Feedback - Perceived Mouthful - Using Kangertech Subox Mini C (Sub-ohm Device)

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout

    The perceived mouthful will be assessed using the following question: "How would you rate the amount of smoke filling your mouth during the puff you just smoked?". A subjective visual analog scale will be used (1-5, barely any smoke- a lot of smoke) with higher scores indicating higher mouthful. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.

  10. Sensory Feedback - Perceived Draw Effort - Using Kangertech Subox Mini C (Sub-ohm Device)

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout

    The perceived draw effort will be assessed using the following question: " How would you rate the effort needed to draw the puff you just smoked?". A subjective visual analog scale will be used (1-5, easy- hard) with higher scores indicating harder draw effort. Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.

  11. Sensory Feedback - Throat Hit - Using Kangertech Subox Mini C (Sub-ohm Device)

    Time frame: Will be measured during the approximately 5-minute, 10-puff use bout

    The perceived Throat hit will be assessed using the following question: "How would you describe the throat hit of the device you just used" (0-100 General Labeled Magnitude Scale; anchors: "barely detectable" to "strongest imaginable"). Puffs were administered in alternating order using block randomization; for Combination Six, odd puffs were delivered at 20W and even puffs at 40W; for Combination Seven, odd puffs were delivered at 20W/8mg/mL and even puffs at 40W/4mg/mL; for Combination Eight, odd puffs were delivered at 30/70 PG/VG and even puffs at 70/30 PG/VG.

Sponsors and collaborators

Lead sponsor

American University of Beirut Medical Center

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)
  • National Institutes of Health (NIH)

Registry information

Official study title

Nicotine Flux, a Potentially Powerful Tool for Regulating Nicotine Delivery From Electronic Cigarettes: Significance of Nicotine Flux to the Rate of Nicotine Delivery and Subjective Effect

Important dates

Study start
2022
Primary completion
2025
Study completion
2025
First posted
Jun 24, 2022
Registry last updated
Sep 18, 2026

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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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