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

NCT04038515 | Completed Phase 2 DMC FDA Drug

• 3 other identifiers: 2000029704R01DA0463602000025408
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Nicotine; E-liquid Flavors

Keywords

Menthol; Electronic Nicotine Delivery Systems

Outcome Measures

Primary Outcomes (2)

• Subjective drug ratings

  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).

  immediately after intervention

• E-cigarette use

  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).

  immediately after intervention

Study Arms (4)

E-liquid Order 'A'

EXPERIMENTAL

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; 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'

E-liquid Order 'B'

EXPERIMENTAL

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; 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'

E-liquid Order 'C'

EXPERIMENTAL

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; 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'

E-liquid Order 'D'

EXPERIMENTAL

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; 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'

Interventions

Nicotine 0 mg/mL DRUG

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).

Also known as: nicotine

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

Nicotine 6 mg/mL DRUG

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).

Also known as: nicotine

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

Nicotine 12 mg/mL DRUG

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).

Also known as: nicotine

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

Nicotine 24 mg/mL DRUG

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).

Also known as: nicotine

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

'Menthol' flavor OTHER

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).

Also known as: menthol

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

'Menthol/Mint' flavor OTHER

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).

Also known as: menthol

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

'Green Apple' flavor OTHER

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).

Also known as: fruit

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

'Watermelon' flavor OTHER

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).

Also known as: fruit

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

'Unflavored' OTHER

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).

Also known as: unflavored

E-liquid Order 'A'; E-liquid Order 'B'; E-liquid Order 'C'; E-liquid Order 'D'

Eligibility Criteria

• Age: 18 Years - 30 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Yale University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Yale University School of Medicine

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Vaping

Interventions

Nicotine; Menthol; Fruit

Condition Hierarchy (Ancestors)

Smoking; Behavior

Intervention Hierarchy (Ancestors)

Solanaceous Alkaloids; Alkaloids; Heterocyclic Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Elise DeVito, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 24, 2019
• First Posted: July 30, 2019
• Study Start: October 27, 2022
• Primary Completion: June 3, 2024
• Study Completion: June 3, 2024
• Last Updated: August 5, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)