Impact of Flavors on Nicotine Perception and Self-Administration Via E-cigarettes

Yale University

Status and phase

Completed

Phase 2

Conditions

Nicotine

E-liquid Flavors

Treatments

Drug: Nicotine 6 mg/mL

Other: 'Watermelon' flavor

Other: 'Green Apple' flavor

Drug: Nicotine 12 mg/mL

Other: 'Menthol/Mint' flavor

Other: 'Menthol' flavor

Drug: Nicotine 24 mg/mL

Drug: Nicotine 0 mg/mL

Other: 'Unflavored'

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT04038515

2000029704

2000025408 (Other Identifier)

R01DA046360 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The goal of this application is to test whether menthol and fruit flavors impact e-cigarette use through dissociable mechanisms and exert their effects differentially across nicotine doses.

Full description

This study examines the impact of menthol and fruit flavors on self-administration of e-cigarette solutions containing varying amounts of nicotine. This is a randomized, double-blind study with a within-subject cross-over design, using e-liquids with 5 different flavors and 4 different levels of nicotine for a total of 20 different e-liquid formulations. Each subject will participate in 4 test sessions. The order of flavor and nicotine delivery will be randomized. At each test session, they will undergo directed self-administration, in a randomized order, then an ad libitum self-administration session where they can choose among all of the e-cigarettes used during the directed session. The primary aims assess the impacts of nicotine and flavor (and their interactions) on participants' subjective ratings of the e-liquids during the 'directed' self-administration component, and self-administered puffs during the ad libitum self-administration component. In addition, the study will explore the impact of sex/gender and sensitivity to nicotine aversiveness or bitterness (as operationalized by genetic variations in the alpha-5 subunit of nicotinic acetylcholine receptor that influences the aversive effects of nicotine, or a taste receptor number 38 ( TAS2R38) important for bitterness perception) on study outcomes.

Enrollment

54 patients

Sex

All

Ages

18 to 30 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

INCLUSION CRITERIA

Aged 18 to 30;
Past month daily nicotine-containing e-cigarette, cigarette, and/or cigar/little cigar/cigarillo use;
Urine cotinine levels consistent with regular nicotine use (e.g., NicAlert urine cotinine dipstick ≥3 or Accutest Positive for Cotinine);
For females, using acceptable birth control methods;
Able to provide written informed consent;
Able to read and write in English;
Stated willingness to comply with all study procedures (including self-administration of all e-liquid conditions; attend in-person sessions; comply with COVID guidelines of the research facilities) and lifestyle considerations (including overnight nicotine abstinence) and availability for the duration of the study;
Cardiovascular measures in normal/ non-hypertensive range for adults, including resting heart rate (HR) of 60-100 bpm; blood pressure (BP) of equal to or less than 129 mmHg (systolic)/80 mmHg (diastolic)); and oximeter (i.e., blood oxygenation) readings of 95-100 SpO2;
Resident of the State of Connecticut.

Exclusion Criteria:

Any allergy or known hypersensitivity to propylene glycol, vegetable glycerin, menthol, mint, green apple or watermelon flavorants or history of allergic or hypersensitive reaction to use of an e-cigarette/vaping device;
Has not used e-cigarettes at least 10 times in the last 6 months;
For females, pregnant (as determined by pregnancy screening) or breast feeding;
Seeking (or undergoing) treatment for nicotine dependence or tobacco product use (smoking or vaping) or has current plans to quit tobacco product use;
Meet current criteria for psychiatric disorder (according to the MINI);
Current or history of respiratory illnesses including pneumonia with COVID-19 , other medical illness, and/or psychotropic medication use that a clinician investigator deems a contraindication for study participation.
History of environmental - bronchospastic allergies, multiple chemical sensitivities, or other airway sensitivities that require the use of an epi pen or that in the investigators view would make it risky for participation;
Not fully vaccinated for COVID-19

Trial design

Primary purpose

Other

Allocation

Randomized

Interventional model

Crossover Assignment

Masking

Double Blind

54 participants in 4 patient groups

E-liquid Order 'A'

Experimental group

Description:

Order 'A' for E-liquid Self-Administration: All participants will be given all e-liquids (i.e., all 20 nicotine\*flavor combinations (4 nicotine\* 5 flavor combinations)) in this within-subject, cross-over design study. Participants will be randomized the order in which they self-administer the 20 nicotine\*flavor combinations of e-liquid (across and within the 4 visits). The specific order cannot be described here without disrupting the double-blind nature of the study design.

Treatment:

Other: 'Unflavored'

Drug: Nicotine 0 mg/mL

Drug: Nicotine 24 mg/mL

Other: 'Menthol/Mint' flavor

Other: 'Menthol' flavor

Other: 'Green Apple' flavor

Drug: Nicotine 12 mg/mL

Other: 'Watermelon' flavor

Drug: Nicotine 6 mg/mL

E-liquid Order 'B'

Experimental group

Description:

Order 'B' for E-liquid Self-Administration: All participants will be given all e-liquids (i.e., all 20 nicotine\*flavor combinations (4 nicotine\* 5 flavor combinations)) in this within-subject, cross-over design study. Participants will be randomized the order in which they self-administer the 20 nicotine\*flavor combinations of e-liquid (across and within the 4 visits). The specific order cannot be described here without disrupting the double-blind nature of the study design.

Treatment:

Other: 'Unflavored'

Drug: Nicotine 0 mg/mL

Drug: Nicotine 24 mg/mL

Other: 'Menthol/Mint' flavor

Other: 'Menthol' flavor

Other: 'Green Apple' flavor

Drug: Nicotine 12 mg/mL

Other: 'Watermelon' flavor

Drug: Nicotine 6 mg/mL

E-liquid Order 'C'

Experimental group

Description:

One nicotine level condition is a medium nicotine e-liquid (12 mg/mL nicotine). All participants will be given all e-liquids (i.e., all 20 nicotine\*flavor combinations (4 nicotine\* 5 flavor combinations)) in this within-subject, cross-over design study. Participants will be randomized the order in which they self-administer the 20 nicotine\*flavor combinations of e-liquid (across and within the 4 visits). The specific order cannot be described here without disrupting the double-blind nature of the study design.

Treatment:

Other: 'Unflavored'

Drug: Nicotine 0 mg/mL

Drug: Nicotine 24 mg/mL

Other: 'Menthol/Mint' flavor

Other: 'Menthol' flavor

Other: 'Green Apple' flavor

Drug: Nicotine 12 mg/mL

Other: 'Watermelon' flavor

Drug: Nicotine 6 mg/mL

E-liquid Order 'D'

Experimental group

Description:

One nicotine level condition is a high nicotine e-liquid (24 mg/mL nicotine). All participants will be given all e-liquids (i.e., all 20 nicotine\*flavor combinations (4 nicotine\* 5 flavor combinations)) in this within-subject, cross-over design study. Participants will be randomized the order in which they self-administer the 20 nicotine\*flavor combinations of e-liquid (across and within the 4 visits). The specific order cannot be described here without disrupting the double-blind nature of the study design.

Treatment:

Other: 'Unflavored'

Drug: Nicotine 0 mg/mL

Drug: Nicotine 24 mg/mL

Other: 'Menthol/Mint' flavor

Other: 'Menthol' flavor

Other: 'Green Apple' flavor

Drug: Nicotine 12 mg/mL

Other: 'Watermelon' flavor

Drug: Nicotine 6 mg/mL