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

Sponsor
Yale University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT04038515
Collaborator
National Institute on Drug Abuse (NIDA) (NIH)
60
1
4
11
5.5

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Nicotine 0 mg/mL
  • Drug: Nicotine 6 mg/mL
  • Drug: Nicotine 12 mg/mL
  • Drug: Nicotine 24 mg/mL
  • Other: 'Menthol' flavor
  • Other: 'Menthol/Mint' flavor
  • Other: 'Green Apple' flavor
  • Other: 'Watermelon' flavor
  • Other: 'Unflavored'
Phase 2

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
60 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Intervention Model Description:
This is a within-subject, cross-over design. Participants will be invited to complete 4 test sessions. Across those 4 test sessions, participants will self-administer e-cigarettes containing all 20 e-liquid conditions (4 nicotine * 5 flavor conditions) in both 'directed' and ad libitum self-administration study components. The order of nicotine and flavor will be randomized across participants.This is a within-subject, cross-over design. Participants will be invited to complete 4 test sessions. Across those 4 test sessions, participants will self-administer e-cigarettes containing all 20 e-liquid conditions (4 nicotine * 5 flavor conditions) in both 'directed' and ad libitum self-administration study components. The order of nicotine and flavor will be randomized across participants.
Masking:
Double (Participant, Investigator)
Masking Description:
This is a double-blind study. Although participants will receive all conditions in this within-subject cross-over study, the participant and researcher will be blinded to the order of e-liquid conditions (nicotine level, flavor) across and within test sessions.
Primary Purpose:
Other
Official Title:
Impact of Flavors on Nicotine Perception and Self-Administration Via E-cigarettes
Anticipated Study Start Date :
Jun 30, 2022
Anticipated Primary Completion Date :
May 31, 2023
Anticipated Study Completion Date :
May 31, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: E-liquid Order 'A'

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.

Drug: Nicotine 0 mg/mL
E-liquid containing no nicotine (0 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
Other Names:
  • nicotine
  • Drug: Nicotine 6 mg/mL
    E-liquid containing low nicotine (6 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 12 mg/mL
    E-liquid containing medium nicotine ( 12 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 24 mg/mL
    E-liquid containing high nicotine ( 24 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Other: 'Menthol' flavor
    E-liquid containing 'menthol' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Menthol/Mint' flavor
    E-liquid containing 'menthol/mint' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Green Apple' flavor
    E-liquid containing 'green apple' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Watermelon' flavor
    E-liquid containing 'watermelon' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Unflavored'
    E-liquid containing no additional flavor (i.e., 'unflavored') will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • unflavored
  • Experimental: E-liquid Order 'B'

    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.

    Drug: Nicotine 0 mg/mL
    E-liquid containing no nicotine (0 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 6 mg/mL
    E-liquid containing low nicotine (6 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 12 mg/mL
    E-liquid containing medium nicotine ( 12 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 24 mg/mL
    E-liquid containing high nicotine ( 24 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Other: 'Menthol' flavor
    E-liquid containing 'menthol' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Menthol/Mint' flavor
    E-liquid containing 'menthol/mint' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Green Apple' flavor
    E-liquid containing 'green apple' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Watermelon' flavor
    E-liquid containing 'watermelon' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Unflavored'
    E-liquid containing no additional flavor (i.e., 'unflavored') will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • unflavored
  • Experimental: E-liquid Order 'C'

    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.

    Drug: Nicotine 0 mg/mL
    E-liquid containing no nicotine (0 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 6 mg/mL
    E-liquid containing low nicotine (6 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 12 mg/mL
    E-liquid containing medium nicotine ( 12 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 24 mg/mL
    E-liquid containing high nicotine ( 24 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Other: 'Menthol' flavor
    E-liquid containing 'menthol' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Menthol/Mint' flavor
    E-liquid containing 'menthol/mint' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Green Apple' flavor
    E-liquid containing 'green apple' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Watermelon' flavor
    E-liquid containing 'watermelon' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Unflavored'
    E-liquid containing no additional flavor (i.e., 'unflavored') will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • unflavored
  • Experimental: E-liquid Order 'D'

    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.

    Drug: Nicotine 0 mg/mL
    E-liquid containing no nicotine (0 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 6 mg/mL
    E-liquid containing low nicotine (6 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 12 mg/mL
    E-liquid containing medium nicotine ( 12 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Drug: Nicotine 24 mg/mL
    E-liquid containing high nicotine ( 24 mg/mL nicotine) will be self-administered via e-cigarettes. This will be administered in 5 flavor conditions (1 unflavored, 2 menthol, and 2 fruit conditions).
    Other Names:
  • nicotine
  • Other: 'Menthol' flavor
    E-liquid containing 'menthol' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Menthol/Mint' flavor
    E-liquid containing 'menthol/mint' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • menthol
  • Other: 'Green Apple' flavor
    E-liquid containing 'green apple' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Watermelon' flavor
    E-liquid containing 'watermelon' flavor will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • fruit
  • Other: 'Unflavored'
    E-liquid containing no additional flavor (i.e., 'unflavored') will be self-administered via e-cigarettes. This will be administered in 4 nicotine conditions (0, 6, 12, 24 mg/mL nicotine).
    Other Names:
  • unflavored
  • Outcome Measures

    Primary Outcome Measures

    1. Subjective drug ratings [immediately after intervention]

      Subjective ratings of e-liquids delivered via e-cigarette will be assessed during the 'directed' self-administration component of each test day, using visual analogue scales (VAS). VAS scores range from 0=not at all to 100=extremely. Separate VAS scales will be collected for subjective ratings of aversive properties (higher scores reflect more aversiveness) and rewarding properties (higher scores reflect more rewarding properties) of the e-cigarettes, in each nicotine*flavor condition. Subjective drug ratings for each nicotine*flavor condition will be tested at one test day only and the order of nicotine*flavor conditions will be randomized across the test days (and order within test days will be randomized).

    2. E-cigarette use [immediately after intervention]

      Number of puffs from each e-cigarette (containing different e-liquids) will be measured during the ad libitum self-administration component of each test day. E-cigarette use (ad libitum puffs) for each nicotine*flavor condition will be tested at one test day only and the order of nicotine*flavor conditions will be randomized across the test days (and order within test days will be randomized).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 30 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Past month daily cigarette, nicotine-containing e-cigarette, and/or cigar/little cigar/cigarillo use.

    • Urine cotinine levels consistent with regular nicotine use

    • For women, using acceptable birth control methods

    • Able to read and write English

    Exclusion Criteria:
    • Current or history of major medical illness psychiatric diagnosis or substance use or psychotropic medication use that the physician investigator deems a contraindication for study participation

    • Current psychiatric diagnosis of bipolar affective disorder, schizophrenia, homicidal or suicidal ideation

    • Any allergy to propylene glycol, vegetable glycerin, menthol, mint, green apple or watermelon flavorants

    • For women, pregnant as determined by pregnancy screening, or breast feeding

    • Seeking (or undergoing) treatment for nicotine dependence or smoking

    • Inability/unwillingness to fulfill scheduled visits and procedures including directed self-administration of all e-liquid flavors

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Yale University School of Medicine New Haven Connecticut United States 06511

    Sponsors and Collaborators

    • Yale University
    • National Institute on Drug Abuse (NIDA)

    Investigators

    • Principal Investigator: Elise DeVito, PhD, Yale University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Yale University
    ClinicalTrials.gov Identifier:
    NCT04038515
    Other Study ID Numbers:
    • 2000029704
    • R01DA046360
    • 2000025408
    First Posted:
    Jul 30, 2019
    Last Update Posted:
    May 31, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Yale University
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 31, 2022