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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04038515
Recruitment Status : Not yet recruiting
First Posted : July 30, 2019
Last Update Posted : August 2, 2019
Sponsor:
Information provided by (Responsible Party):
Yale University

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
Nicotine Vaping 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 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.
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
Estimated Study Start Date : August 15, 2019
Estimated Primary Completion Date : June 15, 2022
Estimated Study Completion Date : June 15, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: E-Cigarettes

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: 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 Name: unflavored




Primary Outcome Measures :
  1. Subjective drug ratings [ Time Frame: 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 [ Time Frame: 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).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04038515


Contacts
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Contact: Elise DeVito, PhD 203-737-4882 elise.devito@yale.edu

Locations
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United States, Connecticut
Yale University School of Medicine Not yet recruiting
New Haven, Connecticut, United States, 06511
Contact: Elise DeVito, PhD    203-737-4882    elise.devito@yale.edu   
Sponsors and Collaborators
Yale University
Investigators
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Principal Investigator: Elise DeVito, PhD Yale University

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Responsible Party: Yale University
ClinicalTrials.gov Identifier: NCT04038515     History of Changes
Other Study ID Numbers: 2000025408
First Posted: July 30, 2019    Key Record Dates
Last Update Posted: August 2, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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:
Menthol
Electronic Nicotine Delivery Systems
Additional relevant MeSH terms:
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Menthol
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Antipruritics
Dermatologic Agents