Effects of Novel E-cigarette Constituents on Adults TCORS 3.0

June 12, 2026 updated by: Yale University

Examining Appeal and Addiction Potential of Novel E-cigarette Constituents Among Adults

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The investigators will examine the influence of cooling components of WS-3, WS-23 (synthetic coolants) and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults. Participants will rate the flavor intensity, coolness, sweetness, and irritation/harshness, bitterness experienced using validated rating scales. 66 adult participants (18+ years of age) who are current e-cigarette users will participate in 3 laboratory sessions. Participants will be randomized to receive one of the 3 menthol conditions (no-menthol, low menthol, high menthol) in Lab 1 and will receive the alternative conditions in randomized order in Lab 2 and Lab 3. During each lab session the menthol condition will be paired with three WS-3 concentrations: no WS-3, low (0.1%) WS-3, or high (2.0%) WS-3 and three WS-23 concentrations: low (0.1%) WS-23, high (2.0%) WS-23, or 4% WS-23 in randomized order. All e-cigarettes will contain nicotine salt at a nicotine concentration of ~59mg/ml and all participants will be exposed to eighteen conditions across 3 lab sessions.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
66

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • New Haven, Connecticut, United States, 06519
        • Recruiting
        • JB Pierce Lab

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 18 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

Exclusion Criteria:

  • 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Non-menthol, nicotine 59mg/ml (1)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for non-menthol (1)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Other Names:
  • Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (2)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for non-menthol (2)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Other Names:
  • Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (3)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for non-menthol (3)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Other Names:
  • Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (4)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for non-menthol (4)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Other Names:
  • Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (5)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for non-menthol (5)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Other Names:
  • Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (1)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for low (0.1%) menthol (1)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Other Names:
  • Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (1)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (No WS-3) for high (2.0%) menthol (1)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.
Other Names:
  • Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (2)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for low (0.1%) menthol (2)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Other Names:
  • Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (2)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-3) for high (2.0%) menthol (2)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.
Other Names:
  • Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (3)
Flavor with low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for low (0.1%) menthol (3)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Other Names:
  • Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (3)
Flavor with high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-3) for high (2.0%) menthol (3)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.
Other Names:
  • Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (4)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for low (0.1%) menthol (4)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Other Names:
  • Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (4)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (Low [0.1%] WS-23) for high (2.0%) menthol (4)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-23 concentration.
Other Names:
  • Flavor type
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (5)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for low (0.1%) menthol (5)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Other Names:
  • Flavor type
Experimental: High (2.0%) menthol, nicotine 59mg/ml (5)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (High [2.0%] WS-23) for high (2.0%) menthol (5)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-23 concentration.
Other Names:
  • Flavor type
Experimental: Non-menthol, nicotine 59mg/ml (6)
Flavor without menthol with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for non-menthol (6)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Experimental: Low (0.1%) menthol, nicotine 59mg/ml (6)
Flavor low menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for low (0.1%) menthol (6)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.
Experimental: High (2.0%) menthol, nicotine 59mg/ml (6)
Flavor high menthol concentration with 59mg/ml nicotine
Other: E-liquid coolant (4% WS-23) for high (2.0%) menthol (6)
Adult users of e-cigarette will be exposed to distinct e-liquid coolants with 4% WS-23 concentration.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Liking: Score change in liking/wanting of each e-cigarette condition (5 conditions in total)
Time Frame: 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)
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)
Time Frame: 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)
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)
Time Frame: 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)
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Craving: Change in craving score for e-cigarette from baseline at each e-cigarette condition (5 conditions in total)
Time Frame: 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)
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).
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)
Time Frame: 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)
Saliva samples will be collected following each exposure to product and before each lab sessions to assess change in nicotine/cotinine levels. These levels will be used for correlational analyses with behavioral measures and will be determined using LC/MS techniques at the core laboratory of university.
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Yale University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Suchitra Krishnan-Sarin, PhD, Yale University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 20, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 28, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 28, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
July 6, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 16, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 12, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2000035551_b
  • 2U54DA036151-11 (U.S. NIH Grant/Contract: NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

We may share information about the IPD and study results with other researchers in the future, but the information will be de-identified.

IPD Sharing Time Frame

The identifiable information will be kept for 7 years. After that, the data will become anonymous.

IPD Sharing Access Criteria

The de-identified data will be made available for research purposes by contacting the PI.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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