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

Nicotine Dependence Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05430334
• Other study ID #: American University Of Beirut
• Secondary ID: 1R01DA052565-01A
• Status: Recruiting
• Phase: N/A
• Start date: July 13, 2022
• Est. completion date: January 31, 2025

Study information

• Verified date: December 2023
• Source: American University of Beirut Medical Center
• Contact: Soha Talih, PhD
• Phone: +961-1-350000
• Email: st38[@]aub.edu.lb
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 130
• Est. completion date: January 31, 2025
• Est. primary completion date: September 13, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Nicotine Addiction
• Nicotine Dependence
• Tobacco Use Disorder

Intervention

Combination Product:
• e-liquid 1
30/70 PG/VG ratio with nicotine concentration 4mg/ml protonated
• e-liquid 2
30/70 PG/VG ratio with nicotine concentration 10mg/ml protonated
• e-liquid 3
30/70 PG/VG ratio with nicotine concentration 4mg/ml free base
• e-liquid 4
30/70 PG/VG ratio with nicotine concentration 10mg/ml freebase
• e-liquid 5
30/70 PG/VG ratio with nicotine concentration 0mg/ml (placebo)

Locations

Country	Name	City	State
Lebanon	American University of Beirut	Beirut

Sponsors (3)

Lead Sponsor	Collaborator
American University of Beirut Medical Center	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

Lebanon, 

Outcome

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