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NicotinePhase 2NCT04038515

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

A Phase 2 study testing Nicotine 0 mg/mL, Nicotine 6 mg/mL and Nicotine 12 mg/mL in people with Nicotine and E-liquid Flavors, run by Yale University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 30 yearsHealthy volunteers can take part
Conditions the study is for
Nicotine, E-liquid Flavors
What is being tested?
Nicotine 0 mg/mL, Nicotine 6 mg/mL and Nicotine 12 mg/mL
Could I receive a placebo?
No, everyone receives an active treatment
How many people
54 participants
Where
1 siteUnited States
Study dates
27 Oct 2022to 3 Jun 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 30 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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;
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  • 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.

Who cannot join

  • 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 locations and contacts

1 site in 1 country.

United States1 site
  • Yale University School of Medicine

    New Haven, Connecticut, 06511

Other trials in United States

About this study

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.

Read the 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.

Being tested
Nicotine 0 mg/mL, Nicotine 6 mg/mL, Nicotine 12 mg/mL, Nicotine 24 mg/mL, 'Menthol' flavor
Keywords
Menthol, Electronic Nicotine Delivery Systems
Medical subject headings
Vaping

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Nicotine 0 mg/mLDrug

    Also called nicotine

    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/mLDrug

    Also called nicotine

    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/mLDrug

    Also called nicotine

    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/mLDrug

    Also called nicotine

    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).

  • 'Menthol' flavorOther

    Also called menthol

    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' flavorOther

    Also called menthol

    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' flavorOther

    Also called fruit

    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' flavorOther

    Also called fruit

    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'Other

    Also called 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).

Study groups in NCT04038515
Study groupRoleWhat they receive
E-liquid Order 'A'ExperimentalOrder '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.
Receives: 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'ExperimentalOrder '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.
Receives: 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'ExperimentalOne 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.
Receives: 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'ExperimentalOne 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.
Receives: 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'

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: immediately after intervention

  2. 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).

    Measured: immediately after intervention

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Jul 2019
  2. Study start27 Oct 2022
  3. Primary completion3 Jun 2024
  4. Study completion3 Jun 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
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 blind
Who is masked
Participant, Investigator
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04038515
Sponsor's protocol ID
2000029704
Other IDs
R01DA046360, 2000025408
Status last verified
Aug 2024
First submitted
24 Jul 2019
Last updated
5 Aug 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Nicotine 0 mg/mL, Nicotine 6 mg/mL and Nicotine 12 mg/mL in people with Nicotine and E-liquid Flavors, run by Yale University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Subjective drug ratings (time frame: immediately after intervention). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Aug 2024.

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