Nicotine DependencePhase 1NCT04521647

Effects of Menthol in E-cigarettes on Smoking Behaviors

A Phase 1 study testing Nicotine in people with Nicotine Dependence, 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.

Trial summary

The overall goal of this proposal is to understand the relationship between nicotine metabolism and menthol flavor in e-cigarettes on smoking behavior in smokers. Read more about this study

Who is it for?: Ages 21 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Nicotine Dependence
What is being tested?: Nicotine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 14 participants
Where: 1 siteUnited States
Study dates: 10 May 2022to 25 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 21 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

At least 21 years of age
Able to read and write English.
Smoking at least 1 menthol cigarettes/cigars/little cigars per day
Report regular menthol cigarette use
Have at least 200ng/ml urine cotinine
Willing to abstain from combustible tobacco products 12 hrs prior to each experimental session.

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not planning a smoking quit attempt.
Have not stopped use due to COVID.
used e-cigarettes at least 10 times in the past six months.
Fully vaccinated against COVID-19.
must report history of JUUL and other nicotine salt/pod devices (i.e., JUUL-like)

Who cannot join

Use of psychoactive drugs including anxiolytics, antidepressants, and other psychostimulants unless prescribed and stable for two months.
Current diagnosis of any severe psychiatric disorder
Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, pulmonary or hepatic pathology that would increase risk or would interfere with/mimic tobacco abstinence.
Known hypersensitivity to propylene glycol and nut allergies.
Pregnant or lactating females.
current criteria for moderate or severe cannabis and alcohol use disorder per DSM-5 criteria.

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current criteria for other substance use disorders per DSM-5 criteria.
Seeking treatment to stop smoking.
individuals who do not want to use e-cigarettes.
Uncontrolled asthma (defined as <20 on Asthma Control Test) AND/OR endorsement of "yes" to environmentally induced bronchospasm that requires prescription Epipen)
blood pressure >170/>100 and heart rate >100
vaping of CBD/THC or marijuana related products in the past 3 months
For current THC vapers: Any report of mild or great EVALI-related symptoms (i.e. cough, shortness of breath, chest pain, nausea, vomiting, stomach pain, diarrhea, fever, chills, or weight loss) without non-EVALI reasonable and proximal cause

Trial locations and contacts

1 site in 1 country.

United States1 site

Connecticut Mental Health Center
New Haven, Connecticut, 06519

Other trials in United States

About this study

The overall goal of this proposal is to understand the relationship between nicotine metabolism and menthol flavor in e-cigarettes on smoking behavior in smokers.

Conditions: Nicotine Dependence
Being tested: 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.

NicotineDrug
Participants will receive 5% nicotine in two flavor exposures via e-cigarettes. Each exposure will be 10 3-sec puffs

Study groups in NCT04521647
Study group	Role	What they receive
5% nicotine with menthol flavor and tobacco flavor	Experimental	All participants will receive 5% nicotine/menthol and 5% nicotine/tobacco e-cigarettes over the course of 2 lab sessions; the order of which flavor goes first at each lab session is counterbalanced with half getting menthol flavor first and half getting tobacco flavor first. Receives: Drug: Nicotine

What is being measured

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

Plasma Nicotine Levels
Mean plasma levels obtained after e-cigarette administration at each lab session (lab 1 and lab 2).
Measured: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.
Nicotine Metabolic Rate
Mean Area under the curve (AUC) for plasma nicotine and NMR were computed and then log transformed to reduce skewness of the two measures.
Measured: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.

Timeline

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

10 May 202225 Jul 2023

First posted20 Aug 2020
Study start10 May 2022
Primary completion25 Jul 2023
Study completion25 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.
Other trials for Nicotine DependenceStudies 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: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 14 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04521647
Sponsor's protocol ID: 2000028570
Other IDs: 2U54DA036151-06
Status last verified: Jun 2026
First submitted: 1 Aug 2020
Last updated: 16 Jun 2026
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: No
FDA-regulated device: No

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?

See locations

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All Nicotine Dependence trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Effects of Menthol in E-cigarettes on Smoking Behaviors
ClinicalTrials.gov ID: NCT04521647
Acronym / sponsor ID: 2000028570
Conditions: Nicotine Dependence
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 14 participants (actual)
Lead sponsor: Yale UniversityUniversity, hospital or other
Collaborators: National Institute on Drug Abuse (NIDA)
Study start: 10 May 2022 (actual)
Primary completion: 25 Jul 2023 (actual)
Study completion: 25 Jul 2023 (actual)
First posted: 20 Aug 2020 (actual)
Results: Posted 16 Jun 2026

Clinical summary

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

The overall goal of this proposal is to understand the relationship between nicotine metabolism and menthol flavor in e-cigarettes on smoking behavior in smokers.

Study design

Primary purpose: Other
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
5% nicotine with menthol flavor and tobacco flavor	Experimental	Drug: NicotineAll participants will receive 5% nicotine/menthol and 5% nicotine/tobacco e-cigarettes over the course of 2 lab sessions; the order of which flavor goes first at each lab session is counterbalanced with half getting menthol flavor first and half getting tobacco flavor first.

Who may qualify

Ages: 21 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

At least 21 years of age
Able to read and write English.
Smoking at least 1 menthol cigarettes/cigars/little cigars per day
Report regular menthol cigarette use
Have at least 200ng/ml urine cotinine

Key exclusion criteria (13 listed)

Use of psychoactive drugs including anxiolytics, antidepressants, and other psychostimulants unless prescribed and stable for two months.
Current diagnosis of any severe psychiatric disorder
Any significant current medical condition such as neurological, cardiovascular, endocrine, renal, pulmonary or hepatic pathology that would increase risk or would interfere with/mimic tobacco abstinence.
Known hypersensitivity to propylene glycol and nut allergies.
Pregnant or lactating females.

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
NicotineParticipants will receive 5% nicotine in two flavor exposures via e-cigarettes. Each exposure will be 10 3-sec puffs	Drug	5% nicotine with menthol flavor and tobacco flavor

Primary outcome

Plasma Nicotine Levels
Time frame: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.
Mean plasma levels obtained after e-cigarette administration at each lab session (lab 1 and lab 2).
Nicotine Metabolic Rate
Time frame: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.
Mean Area under the curve (AUC) for plasma nicotine and NMR were computed and then log transformed to reduce skewness of the two measures.

Results and safety

Results posted to the registry on 16 Jun 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Menthol Flavor First, Then Tobacco Flavor	7	5
Tobacco Flavor First, Then Menthol Flavor	7	5

Primary outcome: Plasma Nicotine Levels

Time frame: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.. Mean (Standard Deviation). Unit: ng/mL

Measure	Menthol Nicotine Flavor n = 8	Tobacco Nicotine Flavor n = 8
Value	3.1165000 (2.5275116)	2.8126250 (2.8678062)

Population analysed: Outcomes from 8 participants. 10 participants completed both menthol flavor and tobacco flavor labs (5 in each arm), however the lab/blood analysis was not valid for 2 participants (one in each arm).

Primary outcome: Nicotine Metabolic Rate

Measure	Menthol Nicotine Flavor n = 8	Tobacco Nicotine Flavor n = 8
Value	5.15 (0.56)	5.05 (0.62)

Population analysed: Outcomes from 8 participants; 4 in each arm. 10 participants completed both menthol flavor and tobacco flavor labs, however the lab/blood analysis was not valid for 2 participants.

Adverse events

Time frame: Participant's Adverse Event data was collected from study enrollment through both lab sessions (menthol and nicotine); approximately 3 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Menthol Flavor	0 of 14 (0%)	2 of 14 (14.3%)	0 of 14
Tobacco Flavor	0 of 14 (0%)	0 of 14 (0%)	0 of 14

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Jun 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

The record lists no contact. Use the official record to reach the sponsor.

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 Nicotine in people with Nicotine Dependence, 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 11 inclusion and 13 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 16 Jun 2026. 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 16 Jun 2026). 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?

Plasma Nicotine Levels (time frame: Lab 1 (day 1) and Lab 2 (24 hour minimum / 2 week maximum from Lab 1). During each lab session, plasma levels were collected at baseline, 5, 15, 30, 45 and 60 minutes after e-cigarette exposure.). 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?

On the ClinicalTrials.gov record for NCT04521647.

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 16 Jun 2026.