Effects of Novel E-cigarette Constituents on Adults TCORS 3.0

NCT05932745 | Recruiting DMC

• 2 other identifiers: 2000035551_b2U54DA036151-11
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This study is an examination of the influence of cooling components of WS-3, WS-23, and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults.

Conditions

Nicotine Use Disorder

Keywords

Menthol, cooling components, cigarette, e-cigarette, vaping

Outcome Measures

Primary Outcomes (3)

• Liking: Score change in liking/wanting of each e-cigarette condition (5 conditions in total)

  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).

  Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)

• Reinforcing Efficacy: Score change in drug effects of each e-cigarette condition (5 conditions in total)

  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).

  Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)

• Irritation/Harshness: Score change in irritation of harshness of each e-cigarette condition (5 conditions in total)

  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).

  Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)

Secondary Outcomes (2)

• Craving: Change in craving score for e-cigarette from baseline at each e-cigarette condition (5 conditions in total)

  At baseline (at 0 minute), following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)

• Changes of salivary Nicotine and Cotinine Levels from baseline at each e-cigarette condition (6 conditions in total)

  At baseline (at 0 minute), Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes)...following administration of e-cigarette condition 6 (at 160 minutes)

Study Arms (18)

Non-menthol, nicotine 59mg/ml (1)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (No WS-3) for non-menthol (1)

Low (0.1%) menthol, nicotine 59mg/ml (1)

EXPERIMENTAL

Flavor with low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (No WS-3) for low (0.1%) menthol (1)

High (2.0%) menthol, nicotine 59mg/ml (1)

EXPERIMENTAL

Flavor with high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (No WS-3) for high (2.0%) menthol (1)

Non-menthol, nicotine 59mg/ml (2)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2)

Low (0.1%) menthol, nicotine 59mg/ml (2)

EXPERIMENTAL

Flavor with low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-3) for low (0.1%) menthol (2)

High (2.0%) menthol, nicotine 59mg/ml (2)

EXPERIMENTAL

Flavor with high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-3) for high (2.0%) menthol (2)

Non-menthol, nicotine 59mg/ml (3)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-3) for non-menthol (3)

Low (0.1%) menthol, nicotine 59mg/ml (3)

EXPERIMENTAL

Flavor with low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-3) for low (0.1%) menthol (3)

High (2.0%) menthol, nicotine 59mg/ml (3)

EXPERIMENTAL

Flavor with high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-3) for high (2.0%) menthol (3)

Non-menthol, nicotine 59mg/ml (4)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4)

Low (0.1%) menthol, nicotine 59mg/ml (4)

EXPERIMENTAL

Flavor low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4)

High (2.0%) menthol, nicotine 59mg/ml (4)

EXPERIMENTAL

Flavor high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4)

Non-menthol, nicotine 59mg/ml (5)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-23) for non-menthol (5)

Low (0.1%) menthol, nicotine 59mg/ml (5)

EXPERIMENTAL

Flavor low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5)

High (2.0%) menthol, nicotine 59mg/ml (5)

EXPERIMENTAL

Flavor high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5)

Non-menthol, nicotine 59mg/ml (6)

EXPERIMENTAL

Flavor without menthol with 59mg/ml nicotine

Other: E-liquid coolant (4% WS-23) for non-menthol (6)

Low (0.1%) menthol, nicotine 59mg/ml (6)

EXPERIMENTAL

Flavor low menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (4% WS-23) for low (0.1%) menthol (6)

High (2.0%) menthol, nicotine 59mg/ml (6)

EXPERIMENTAL

Flavor high menthol concentration with 59mg/ml nicotine

Other: E-liquid coolant (4% WS-23) for high (2.0%) menthol (6)

Interventions

E-liquid coolant (No WS-3) for non-menthol (1) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.

Also known as: Flavor type

Non-menthol, nicotine 59mg/ml (1)

E-liquid coolant (No WS-3) for low (0.1%) menthol (1) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.

Also known as: Flavor type

Low (0.1%) menthol, nicotine 59mg/ml (1)

E-liquid coolant (No WS-3) for high (2.0%) menthol (1) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.

Also known as: Flavor type

High (2.0%) menthol, nicotine 59mg/ml (1)

E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Also known as: Flavor type

Non-menthol, nicotine 59mg/ml (2)

E-liquid coolant (Low [0.1%] WS-3) for low (0.1%) menthol (2) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Also known as: Flavor type

Low (0.1%) menthol, nicotine 59mg/ml (2)

E-liquid coolant (Low [0.1%] WS-3) for high (2.0%) menthol (2) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.

Also known as: Flavor type

High (2.0%) menthol, nicotine 59mg/ml (2)

E-liquid coolant (High [2.0%] WS-3) for non-menthol (3) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

Also known as: Flavor type

Non-menthol, nicotine 59mg/ml (3)

E-liquid coolant (High [2.0%] WS-3) for low (0.1%) menthol (3) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

Also known as: Flavor type

Low (0.1%) menthol, nicotine 59mg/ml (3)

E-liquid coolant (High [2.0%] WS-3) for high (2.0%) menthol (3) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.

Also known as: Flavor type

High (2.0%) menthol, nicotine 59mg/ml (3)

E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.

Also known as: Flavor type

Non-menthol, nicotine 59mg/ml (4)

E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.

Also known as: Flavor type

Low (0.1%) menthol, nicotine 59mg/ml (4)

E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.

Also known as: Flavor type

High (2.0%) menthol, nicotine 59mg/ml (4)

E-liquid coolant (High [2.0%] WS-23) for non-menthol (5) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.

Also known as: Flavor type

Non-menthol, nicotine 59mg/ml (5)

E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.

Also known as: Flavor type

Low (0.1%) menthol, nicotine 59mg/ml (5)

E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.

Also known as: Flavor type

High (2.0%) menthol, nicotine 59mg/ml (5)

E-liquid coolant (4% WS-23) for non-menthol (6) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.

Non-menthol, nicotine 59mg/ml (6)

E-liquid coolant (4% WS-23) for low (0.1%) menthol (6) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.

Low (0.1%) menthol, nicotine 59mg/ml (6)

E-liquid coolant (4% WS-23) for high (2.0%) menthol (6) OTHER

Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.

High (2.0%) menthol, nicotine 59mg/ml (6)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years or older
• Able to read and write
• Some current e-cigarette use
• Urine cotinine ≥200ng/ml
• Willing to abstain from tobacco/nicotine use 2 hours prior to sessions

You may not qualify if:

• 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
• Dislike of menthol flavor

Sponsors & Collaborators

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

Study Sites (1)

JB Pierce Lab

New Haven, Connecticut, 06519, United States

RECRUITING

Related Publications (1)

• 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.

  PMID: 19833660 BACKGROUND

MeSH Terms

Conditions

Tobacco Use Disorder; Vaping

Interventions

Menthol

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Smoking; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanols; Hexanols; Fatty Alcohols; Alcohols; Organic Chemicals; Cyclohexane Monoterpenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Monoterpenes; Terpenes; Lipids

Study Officials

• Suchitra Krishnan-Sarin, PhD

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Danielle Davis, PhD

CONTACT

203-974-7607; danielle.davis@yale.edu

Wei Li, PhD

CONTACT

wei.vanness.li@yale.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Participants will be given a nicotine containing e-cigarette that could have various levels of cooling flavoring. Participants will not be told the nicotine concentration of the product or the type or concentration of the added coolant or what order it is presented in. Investigator and research assistant (i.e. care provider) will know the doses of nicotine and coolant, but will not know what order coolants are presented to participants.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: All participants receive all 18 study conditions.

Study Record Dates

• First Submitted: June 28, 2023
• First Posted: July 6, 2023
• Study Start: June 20, 2025
• Primary Completion: May 1, 2026
• Study Completion: May 1, 2026
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ANALYTIC CODE
• Time Frame: The identifiable information will be kept for 7 years. After that, the data will become anonymous.
• Access Criteria: The de-identified data will be made available for research purposes by contacting the PI.

Locations

US (1)