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

Nicotine Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT04038515
• Other study ID #: 2000029704
• Secondary ID: R01DA04636020000
• Status: Enrolling by invitation
• Phase: Phase 2
• Start date: October 27, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: January 2024
• Source: Yale University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 60
• Est. completion date: May 31, 2024
• Est. primary completion date: May 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 30 Years

Eligibility

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

Related Conditions & MeSH terms

• E-liquid Flavors
• Nicotine

Intervention

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).
• 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).
• 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).
• 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:
• '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).
• '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).
• '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).
• '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).
• '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).

Locations

Country	Name	City	State
United States	Yale University School of Medicine	New Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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