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

Not Applicable

Recruiting

• Conditions: Nicotine Dependence; Nicotine Vaping; Nicotine Addiction
• Interventions: Combination Product: e-liquid 2; Combination Product: e-liquid 4; Combination Product: e-liquid 1; Combination Product: e-liquid 3; Combination Product: e-liquid 5

• Registration Number: NCT05430334
• Lead Sponsor: American University of Beirut Medical Center

Brief Summary

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.

Detailed Description

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 consisting of 2 bouts (10 puffs + 60min ad libitum) with 2 fluxes (16 and 32μg/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.

Study Timeline

• Study First Submitted: 2022-06-08
• Study First Submitted QC: 2022-06-20
• Study First Posted: 2022-06-24
• Study Start: 2022-07-13
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-20
• Last Update Posted: 2025-02-21
• Primary Completion: 2025-05-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 130

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Combination Two - 32μg/s protonated nicotine flux	e-liquid 2	The investigators will test the subjective effects of nicotine flux (32μg/s) coupled with one ratio of nicotine form (100% protonated). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.
Combination Four - 32μg/s free base nicotine flux	e-liquid 4	The investigators will test the subjective effects of nicotine flux (32μg/s) coupled with one ratio of nicotine form (100% free base). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.
Combination One - 16μg/s protonated nicotine flux	e-liquid 1	The investigators will test the subjective effects of nicotine flux (16μg/s) coupled with one ratio of nicotine form (100% protonated). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.
Combination Three - 16μg/s free base nicotine flux	e-liquid 3	The investigators will test the subjective effects of nicotine flux (16μg/s) coupled with one ratio of nicotine form (100% free base). Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.
Placebo - Combination Five - 0μg/s nicotine flux	e-liquid 5	The investigators will test the subjective effects of nicotine flux (0μg/s) placebo. Following a one-hour observation period, participants will use Subox Mini C in a 10-puff directed (30sec inter-puff interval) bout. One hour after the first bout, participants will be instructed to puff on the device for 60-min ad libitum. Subjective measures (i.e., nicotine dependence, drug effects, product liking, and craving) will be administered 5 times/session: 5 min before and 5 min after onset of the directed bout and 5 min before, halfway into and 5 min after onset of the ad libitum bout.

Primary Outcome Measures

Name	Time	Method
Nicotine Dependence questionnaires - The Fagerstrom Test of Nicotine Dependence	Visit 1 - Before starting the first session	The Fagerstrom Test of Nicotine Dependence questionnaires that assesses nicotine dependence on ENDS. General questions not based on a scale.
Subjective Measures of Nicotine Abstinence Symptoms - PROMIS-10 Global Health measures	Visit 1 - Before starting the first session	The PROMIS-10 Global Health measures five domains: physical function, fatigue, pain, emotional distress, and social health. 10 Items are rated on a five-point scale (Poor=1, Fair=2, Good=3, Very good=4, Excellent=5) with higher scores indicating higher activity.
Subjective Measures of Nicotine Abstinence Symptoms - The corresponding 4-item Combustible cigarette Dependence	Visit 1 - Before starting the first session	The corresponding 4-item Combustible cigarette Dependence Scale that assesses nicotine dependence for daily and nondaily smokers. 4 Items are rated on a five-point scale (Never=1, Rarely=2, Sometimes=3, Often=4, Always=5) with higher scores indicating higher activity.
Subjective Measures of Nicotine Abstinence Symptoms - Drug Effect	Up to 180 minutes	The Drug Effect Questionnaire (DEQ) will measure acute effects consisting of seven items: drug strength, high, feeling stimulated, good effects, bad effects, wanting more drugs, and drug liking and this will be assessed on a subjective scale (0-100, not at all-extremely), with higher scores indicating higher effects.
Subjective Measures of Nicotine Abstinence Symptoms - The corresponding 4-item E-Cigarette Dependence	Visit 1 - Before starting the first session	The corresponding 4-item E-Cigarette Dependence Scale that assesses dependence on ENDS. 4 Items are rated on a five-point scale (Never=1, Rarely=2, Sometimes=3, Often=4, Almost Always=5) with higher scores indicating higher activity.
Subjective Measures of Nicotine Abstinence Symptoms - Product liking magnitude scale	Up to 180 minutes	Product liking will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled magnitude scale (gLMS) on a subjective scale (0-100, not at all - extremely), with higher scores indicating higher effects.
Subjective Measures of Nicotine Abstinence Symptoms - Product liking hedonic scale	Up to 180 minutes	Product liking will be assessed by the Electronic Cigarette Specific Effects questionnaire, general labeled hedonic scale (LHS) (0-100, most disliked sensation imaginable - most liked sensation imaginable), with higher scores indicating higher effects.
Subjective Measures of Nicotine Abstinence Symptoms - Smoking urges	Up to 180 minutes	Smoking urges will be assessed by the smoking urges questionnaire on a subjective scale (0-100, Strongly disagree - strongly agree) with higher scores indicating higher urges.
Subjective Measures of Nicotine Abstinence Symptoms - Hughes and Hatsukami	Up to 180 minutes	The Hughes-Hatsukami Withdrawal Questionnaire (HHWQ) will be assessed by the Hughes and Hatsukami 1986 questionnaire on a subjective scale (0-100, Not at all - extremely).

Secondary Outcome Measures

Name	Time	Method
Number of Puffs	Will be measured during the approximately 60-minute, ad lib use bout	Measured topography Total Number of Puffs (puffs).
Puff Interval	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).
Puff Duration	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout	Measured topography Average Puff Duration (sec).
Flow rate	Will be measured during the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout	Measured topography Average Flow rate (LPM).
Carbonyl compound yield	Will be measured after the 60-minute, ad lib use bout	Total Carbonyls Compounds will be quantified (microg/session).
Liquid consumed	Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout	Liquid consumption for each participant use session will be determined by pre- and post-weighing the ENDS device tank (g/session).
Nicotine flux	Will be measured after the approximately 5-minute, 10-puff use bout and 60-minute, ad lib use bout	Nicotine flux will be quantified (mg/sec).

Trial Locations

Locations (1)

American University of Beirut; 🇱🇧 Beirut, Lebanon