Nicotine Use DisorderPhase 1NCT03634839

Effects of E-cigarette Flavors on Youth TCORS 2.0

A Phase 1 study testing Flavoring Agents and Nicotine in people with Nicotine Use Disorder, 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

This study is an examination of the influence of sweet and cooling flavors on the appeal and abuse potential of nicotine-containing e-cigarettes among susceptible youth. Read more about this study

Who is it for?: Ages 18 to 20 years
Conditions the study is for: Nicotine Use Disorder
What is being tested?: Flavoring Agents and Nicotine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 42 participants
Where: 1 siteUnited States
Study dates: 7 Nov 2022to 20 Jul 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 20 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Ages 18-20 years
Able to read and write
Used e-cigs at least 10 times in lifetime
Used e-cigs in past 30 days

Who cannot join

Current use of non-prescription substances besides nicotine, marijuana, alcohol
Any significant current medical or psychiatric condition
Known hypersensitivity to propylene glycol
Pregnant or lactating females
Uncontrolled asthma
Nut/e-liquid flavorant allergy
current marijuana (tetrahydrocannabinol) vaping + E-cigarette or vaping use Associated Lung Injury (EVALI) symptoms

Trial locations and contacts

1 site in 1 country.

United States1 site

CMHC, Substance Abuse Center
New Haven, Connecticut, 06519

Other trials in United States

About this study

Official title: Effects of E-cigarette Flavors on Youth

This study is an examination of the influence of sweet and cooling flavors on the appeal and abuse potential of nicotine-containing e-cigarettes among susceptible youth.

Read the detailed description

Researchers will examine the influence of sweet and cooling flavors on the appeal and abuse potential of nicotine-containing e-cigarettes among susceptible youth. Participants will rate the flavor intensity, coolness, sweetness, and irritation experienced using validated rating scales. Forty youth (18-20 years of age) who have experience with e-cigarettes and will participate in 1 laboratory session. They will receive 1 nicotine concentrations (36mg/ml nicotine salt) during the session; during the session they will be exposed, in random order, to sweet (watermelon) and sweet-cooling (watermelon-menthol) flavors combined with the assigned session nicotine concentration.

Conditions: Nicotine Use Disorder
Being tested: Flavoring Agents, Nicotine
Medical subject headings: Tobacco Use Disorder

What participants receive

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

Flavoring AgentsDrug
Also called Cooling flavor
Flavor of e-liquid - sweet or tobacco
NicotineDrug
Also called Nicotine concentration
Nicotine level (36 mg/ml)

Study groups in NCT03634839
Study group	Role	What they receive
Sweet non-menthol, nicotine 36mg/ml	Experimental	Sweet flavor non-menthol (Watermelon) with 36mg/ml Nicotine Receives: Drug: Flavoring Agents; Drug: Nicotine
Sweet menthol, nicotine 36mg/ml	Experimental	Sweet flavor with menthol (Watermelon-menthol) with 36mg/ml Nicotine Receives: Drug: Flavoring Agents; Drug: Nicotine

What is being measured

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

Liking: Difference Score in Liking/Wanting of Each E-cigarette Condition
The Labeled Hedonic Scale will be used to ask about liking and wanting of the e-cigarette (one item Visual Analog Scale with ratings ranging from "most disliked sensation imaginable" to "most liked sensation imaginable" with higher values indicating greater liking). Specific scale semantic structure and corresponding values: most disliked imaginable=-100, dislike extremely=-62.9, dislike very much=-41.6, dislike moderately=-17.6, dislike slightly=-5.9, neutral=0, like slightly=6.3, like moderately=17.8, like very much=44.4, like extremely=65.7, most liked imaginable=100.
Measured: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Reinforcing Efficacy: Difference Score in Drug Effects of Each E-cigarette Condition
Difference between e-cigarette effects for each e-cigarette condition as measured by the computerized version of the Drug Effects Questionnaire (DEQ). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. A modified version of the Drug Effects Questionnaire (DEQ) will be used in which participants rate acute responses to the e-cigarette on a 0-100mm scale from "not at all" (0mm) to "extremely" (100mm). Higher values indicate stronger reinforcing efficacy (i.e., wanting/liking effects).
Measured: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Craving: Change in Craving Score for E-cigarette
Difference from baseline in craving for each e-cigarette condition will be measured by the Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their craving for e-cigarettes using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).
Measured: At baseline (+0 minutes), Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Irritation/Harshness: Difference Score in Irritation of Harshness of Each E-cigarette Condition
Difference in irritation at each e-cigarette condition as measured by the computerized Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).
Measured: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)

Timeline

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

7 Nov 202220 Jul 2023

First posted17 Aug 2018
Study start7 Nov 2022
Primary completion16 Jun 2023
Study completion20 Jul 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Nicotine Use DisorderStudies of the same condition, open and under way.
More trials run by Yale UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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 1
Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 42 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03634839
Sponsor's protocol ID: 2000023077-1
Other IDs: 2U54DA036151-06
Status last verified: Jul 2024
First submitted: 13 Aug 2018
Last updated: 9 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Lim J, Wood A, Green BG. Derivation and evaluation of a labeled hedonic scale. Chem Senses. 2009 Nov;34(9):739-51. doi: 10.1093/chemse/bjp054.
PubMed 19833660
Li W, Davis DR, Wu R, Gueorguieva R, Green BG, Krishnan-Sarin S. The effect of "ice" components in sweet-flavored nicotine-containing e-liquids among young adult e-cigarette users. Exp Clin Psychopharmacol. 2025 Oct;33(5):477-482. doi: 10.1037/pha0000786. Epub 2025 Jun 9.
PubMed 40489161

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 9 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of E-cigarette Flavors on Youth
ClinicalTrials.gov ID: NCT03634839
Acronym / sponsor ID: 2000023077-1
Conditions: Nicotine Use Disorder
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 42 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 7 Nov 2022 (actual)
Primary completion: 16 Jun 2023 (actual)
Study completion: 20 Jul 2023 (actual)
First posted: 17 Aug 2018 (actual)
Results: Posted 9 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

This study is an examination of the influence of sweet and cooling flavors on the appeal and abuse potential of nicotine-containing e-cigarettes among susceptible youth.

Detailed description

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Sweet non-menthol, nicotine 36mg/ml	Experimental	Drug: Flavoring Agents, Drug: NicotineSweet flavor non-menthol (Watermelon) with 36mg/ml Nicotine
Sweet menthol, nicotine 36mg/ml	Experimental	Drug: Flavoring Agents, Drug: NicotineSweet flavor with menthol (Watermelon-menthol) with 36mg/ml Nicotine

Who may qualify

Ages: 18 to 20 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (4 listed)

Ages 18-20 years
Able to read and write
Used e-cigs at least 10 times in lifetime
Used e-cigs in past 30 days

Key exclusion criteria (7 listed)

Current use of non-prescription substances besides nicotine, marijuana, alcohol
Any significant current medical or psychiatric condition
Known hypersensitivity to propylene glycol
Pregnant or lactating females
Uncontrolled asthma

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Flavoring AgentsAlso: Cooling flavorFlavor of e-liquid - sweet or tobacco	Drug	Sweet menthol, nicotine 36mg/ml, Sweet non-menthol, nicotine 36mg/ml
NicotineAlso: Nicotine concentrationNicotine level (36 mg/ml)	Drug	Sweet menthol, nicotine 36mg/ml, Sweet non-menthol, nicotine 36mg/ml

Primary outcome

Liking: Difference Score in Liking/Wanting of Each E-cigarette Condition
Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
The Labeled Hedonic Scale will be used to ask about liking and wanting of the e-cigarette (one item Visual Analog Scale with ratings ranging from "most disliked sensation imaginable" to "most liked sensation imaginable" with higher values indicating greater liking). Specific scale semantic structure and corresponding values: most disliked imaginable=-100, dislike extremely=-62.9, dislike very much=-41.6, dislike moderately=-17.6, dislike slightly=-5.9, neutral=0, like slightly=6.3, like moderately=17.8, like very much=44.4, like extremely=65.7, most liked imaginable=100.
Reinforcing Efficacy: Difference Score in Drug Effects of Each E-cigarette Condition
Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Difference between e-cigarette effects for each e-cigarette condition as measured by the computerized version of the Drug Effects Questionnaire (DEQ). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. A modified version of the Drug Effects Questionnaire (DEQ) will be used in which participants rate acute responses to the e-cigarette on a 0-100mm scale from "not at all" (0mm) to "extremely" (100mm). Higher values indicate stronger reinforcing efficacy (i.e., wanting/liking effects).
Craving: Change in Craving Score for E-cigarette
Time frame: At baseline (+0 minutes), Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Difference from baseline in craving for each e-cigarette condition will be measured by the Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their craving for e-cigarettes using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).
Irritation/Harshness: Difference Score in Irritation of Harshness of Each E-cigarette Condition
Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)
Difference in irritation at each e-cigarette condition as measured by the computerized Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: "no sensation", "barely detectable", "weak", "moderate", "strong", "very strong", and "strongest imaginable", positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end).

Results and safety

Results posted to the registry on 9 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sweet Non-menthol Then Sweet Menthol, Each With Nicotine 36mg/ml	20	20
Sweet Menthol Then Sweet Non-menthol, Each With Nicotine 36mg/ml	22	20

Primary outcome: Liking: Difference Score in Liking/Wanting of Each E-cigarette Condition

Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40). Least squares mean (Standard Error). Unit: score on a scale

Measure	Sweet Non-menthol, Nicotine 36mg/ml n = 40	Sweet Menthol, Nicotine 36mg/ml n = 40
Value	1.268 (3.158)	-3.916 (3.158)

Sweet Non-menthol, Nicotine 36mg/ml vs Sweet Menthol, Nicotine 36mg/ml: Mean Difference (Final Values): -5.184, p = 0.053, t-test, 2 sided

Population analysed: After each of the two puff bouts, we evaluated participants' reference for the overall experience of the e-cigarette using the LHS, which is a bipolar category ratio scale that spans from -100 (most disliked) to 100 (most liked), with 'neither liked nor disliked' positioned as the midpoint. The scale labels were places along the scale based on their semantic magnitude.

Primary outcome: Reinforcing Efficacy: Difference Score in Drug Effects of Each E-cigarette Condition

Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40). Least squares mean (Standard Error). Unit: score on a scale

Measure	Sweet Non-menthol, Nicotine 36mg/ml n = 40	Sweet Menthol, Nicotine 36mg/ml n = 40
Value	37.06 (3.01)	35.18 (3.01)

Sweet Non-menthol, Nicotine 36mg/ml vs Sweet Menthol, Nicotine 36mg/ml: Mean Difference (Final Values): -1.881, p = 0.187, t-test, 2 sided

Population analysed: To examine wanting/liking, we used subscales from the Drug Effects Questionnaire (DEQ), following the approach established in previous literature. Four items were used to measure wanting/liking effects (the average of 'I feel good e-cigarette effects', 'I want more of that e-cigarette I received', 'I feel the e-cigarette strength', and 'I like the e-cigarette effect').

Primary outcome: Craving: Change in Craving Score for E-cigarette

Time frame: At baseline (+0 minutes), Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40). Least squares mean (Standard Error). Unit: score on a scale

Measure	Sweet Non-menthol, Nicotine 36mg/ml n = 40	Sweet Menthol, Nicotine 36mg/ml n = 40
Value	2.72 (0.22)	2.43 (0.22)

Sweet Non-menthol, Nicotine 36mg/ml vs Sweet Menthol, Nicotine 36mg/ml: Mean Difference (Final Values): -0.286, p = 0.135, t-test, 2 sided

Primary outcome: Irritation/Harshness: Difference Score in Irritation of Harshness of Each E-cigarette Condition

Time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40). Least squares mean (Standard Error). Unit: score on a scale

Measure	Sweet Non-menthol, Nicotine 36mg/ml n = 40	Sweet Menthol, Nicotine 36mg/ml n = 40
Value	20.92 (1.68)	22.86 (1.68)

Sweet Non-menthol, Nicotine 36mg/ml vs Sweet Menthol, Nicotine 36mg/ml: Mean Difference (Final Values): 1.942, p = 0.210, t-test, 2 sided

Adverse events

Time frame: Two hours during a single lab session. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Sweet Non-menthol With Nicotine 36mg/ml	0 of 40 (0%)	0 of 40 (0%)	0 of 40
Sweet Menthol With Nicotine 36mg/ml	0 of 42 (0%)	2 of 42 (4.8%)	0 of 42

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 19833660Lim J, Wood A, Green BG. Derivation and evaluation of a labeled hedonic scale. Chem Senses. 2009 Nov;34(9):739-51. doi: 10.1093/chemse/bjp054.
Derived from this study: PubMed 40489161Li W, Davis DR, Wu R, Gueorguieva R, Green BG, Krishnan-Sarin S. The effect of "ice" components in sweet-flavored nicotine-containing e-liquids among young adult e-cigarette users. Exp Clin Psychopharmacol. 2025 Oct;33(5):477-482. doi: 10.1037/pha0000786. Epub 2025 Jun 9.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Suchitra Krishnan-Sarin, PhD principal investigator

Yale University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Flavoring Agents and Nicotine in people with Nicotine Use Disorder, 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 4 inclusion and 7 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 9 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Liking: Difference Score in Liking/Wanting of Each E-cigarette Condition (time frame: Following administration of e-cigarette condition 1 (+10 minutes), following administration of e-cigarette condition 2 (+40)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03634839, which also lists 2 linked publications.

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 9 Aug 2024.