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

NCT05430334 | Completed

• 2 other identifiers: American University Of Beirut1R01DA052565-01A1
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine Vaping; Nicotine Dependence; Nicotine Addiction

Keywords

Nicotine; Nicotine Flux; Vaping; ENDS; Aerosol; Combustible

Outcome Measures

Primary Outcomes (9)

• Subjective Measures of Nicotine Abstinence Symptoms - PROMIS-10 Global Health measures

  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.

  Visit 1 - Before starting the first session

• Subjective Measures of Nicotine Abstinence Symptoms - The corresponding 4-item E-Cigarette Dependence

  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.

  Visit 1 - Before starting the first session

• Subjective Measures of Nicotine Abstinence Symptoms - The corresponding 4-item Combustible cigarette Dependence

  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.

  Visit 1 - Before starting the first session

• Nicotine Dependence questionnaires - The Fagerstrom Test of Nicotine Dependence

  The Fagerstrom Test of Nicotine Dependence questionnaires that assesses nicotine dependence on ENDS. General questions not based on a scale.

  Visit 1 - Before starting the first session

• Subjective Measures of Nicotine Abstinence Symptoms - Product liking magnitude scale

  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.

  Up to 180 minutes

• Subjective Measures of Nicotine Abstinence Symptoms - Product liking hedonic scale

  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.

  Up to 180 minutes

• Subjective Measures of Nicotine Abstinence Symptoms - Drug Effect

  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.

  Up to 180 minutes

• Subjective Measures of Nicotine Abstinence Symptoms - Smoking urges

  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.

  Up to 180 minutes

• Subjective Measures of Nicotine Abstinence Symptoms - Hughes and Hatsukami

  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).

  Up to 180 minutes

Secondary Outcomes (9)

• Puff Duration

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

• Flow rate

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

• Puff Interval

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

• Number of Puffs

  Will be measured during the approximately 60-minute, ad lib use bout

• Liquid consumed

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

Study Arms (8)

Combination One - 16μg/s protonated nicotine flux

EXPERIMENTAL

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 Product: e-liquid 1

Combination Two - 32μg/s protonated nicotine flux

EXPERIMENTAL

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 Product: e-liquid 2

Combination Three - 16μg/s free base nicotine flux

EXPERIMENTAL

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.

Combination Product: e-liquid 3

Combination Four - 32μg/s free base nicotine flux

EXPERIMENTAL

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 Product: e-liquid 4

Placebo - Combination Five - 0μg/s nicotine flux

PLACEBO COMPARATOR

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.

Combination Product: e-liquid 5

Combination six - 0 ug/s flux; high power/low power

EXPERIMENTAL

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two power levels (20W and 40 W) with no nicotine in the liquid. Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices differing only by the two power levels. Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Combination Product: e-liquid 6

Combination seven - 32 ug/s flux; high power/low power

EXPERIMENTAL

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two power levels (20W and 40 W) and a constant nicotine flux of 32 ug/s. Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices (20 W; 8mg/ml and 40 W;4 mg/ml). Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Combination Product: e-liquid 7 and e-liquid 8

Combination seven - 16 ug/s flux; high PG/VG / low PG/VG

EXPERIMENTAL

The investigators will test the subjective effects (perceived mouthful, perceived draw effort, and throat hit) at two PG/VG ratios (30/70 and 70/30). Participants will alternate 10 directed puffs (30sec inter-puff interval) between two Subox Mini C devices differing only by the two PG/VG ratios. Subjective measures will be administered following puff pairs 1\&2, 5\&6, and 9\&10.

Combination Product: e-liquid 9 and e-liquid 10

Interventions

e-liquid 1 COMBINATION_PRODUCT

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

Combination One - 16μg/s protonated nicotine flux

e-liquid 2 COMBINATION_PRODUCT

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

Combination Two - 32μg/s protonated nicotine flux

e-liquid 3 COMBINATION_PRODUCT

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

Combination Three - 16μg/s free base nicotine flux

e-liquid 4 COMBINATION_PRODUCT

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

Combination Four - 32μg/s free base nicotine flux

e-liquid 5 COMBINATION_PRODUCT

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

Placebo - Combination Five - 0μg/s nicotine flux

e-liquid 6 COMBINATION_PRODUCT

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

Combination six - 0 ug/s flux; high power/low power

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

Combination seven - 32 ug/s flux; high power/low power

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

Combination seven - 16 ug/s flux; high PG/VG / low PG/VG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• American University of Beirut Medical Center: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

American University of Beirut

Beirut, 11-0236, Lebanon

Location

Related Publications (1)

• El-Hellani A, Hanna E, Sharma M, Blohowiak R, Joseph P, Eid T, Nadim H, El-Hage R, Salman R, Karaoghlanian N, Adeniji A, Salam S, Talih F, Elbejjani M, Breland A, Eissenberg T, Shihadeh A, Baldassarri SR, Talih S. Nicotine flux as a powerful tool for regulating nicotine delivery from e-cigarettes: Protocol of two complimentary randomized crossover clinical trials. PLoS One. 2023 Sep 21;18(9):e0291786. doi: 10.1371/journal.pone.0291786. eCollection 2023.

  PMID: 37733666 DERIVED

MeSH Terms

Conditions

Vaping; Tobacco Use Disorder

Condition Hierarchy (Ancestors)

Smoking; Behavior; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Soha Talih, PhD

  American University of Beirut Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Each participant will attend the lab for five different visits that differ by nicotine flux and/or form in random order. All sessions will be double-blind (Participant / Investigator). The analytical chemist will be providing the investigator with e-liquid in a random order in each session for each participant.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant will attend the lab for five different visits that differ by nicotine flux and/or form in random order.

Study Record Dates

• First Submitted: June 8, 2022
• First Posted: June 24, 2022
• Study Start: July 13, 2022
• Primary Completion: July 11, 2025
• Study Completion: July 11, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

LE (1)