Trial Outcomes & Findings for Effects of Menthol in E-cigarettes on Smoking Behaviors (NCT NCT04521647)

NCT ID: NCT04521647

Last Updated: 2026-06-16

Results Overview

Mean plasma levels obtained after e-cigarette administration at each lab session (lab 1 and lab 2).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

14 participants

Primary outcome timeframe

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.

Results posted on

2026-06-16

Participant Flow

All participants will be exposed to the two flavor conditions (tobacco and menthol) in a counterbalanced randomized order. Each lab session exposure will consist of 10 3-sec puffs separated by 30 second intervals and will be separated by a minimum of 24 hours and maximum of 2 weeks.

Participant milestones

Participant milestones
Measure
Menthol Flavor First, Then Tobacco Flavor
Participants were exposed to Menthol then Tobacco flavor with a 60 second washout in between.
Tobacco Flavor First, Then Menthol Flavor
Participants were exposed to Tobacco then Menthol flavor with a 60 second washout in between.
First Lab Session
STARTED
7
7
First Lab Session
COMPLETED
5
5
First Lab Session
NOT COMPLETED
2
2
Between Sessions (2 Days up to 2 Weeks)
STARTED
5
5
Between Sessions (2 Days up to 2 Weeks)
COMPLETED
5
5
Between Sessions (2 Days up to 2 Weeks)
NOT COMPLETED
0
0
Lab Session 2
STARTED
5
5
Lab Session 2
COMPLETED
5
5
Lab Session 2
NOT COMPLETED
0
0

Reasons for withdrawal

Reasons for withdrawal
Measure
Menthol Flavor First, Then Tobacco Flavor
Participants were exposed to Menthol then Tobacco flavor with a 60 second washout in between.
Tobacco Flavor First, Then Menthol Flavor
Participants were exposed to Tobacco then Menthol flavor with a 60 second washout in between.
First Lab Session
Adverse Event
2
0
First Lab Session
Complications with blood draw
0
1
First Lab Session
Withdrawal by Subject
0
1

Baseline Characteristics

Effects of Menthol in E-cigarettes on Smoking Behaviors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Menthol / Nicotine
n=14 Participants
All participants complete both arms described in the protocol section (menthol arm and tobacco arm).
Age, Categorical
<=18 years
0 Participants
n=20 Participants
Age, Categorical
Between 18 and 65 years
14 Participants
n=20 Participants
Age, Categorical
>=65 years
0 Participants
n=20 Participants
Age, Continuous
40.36 years
STANDARD_DEVIATION 9.56 • n=20 Participants
Sex: Female, Male
Female
7 Participants
n=20 Participants
Sex: Female, Male
Male
7 Participants
n=20 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=20 Participants
Race (NIH/OMB)
Asian
0 Participants
n=20 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=20 Participants
Race (NIH/OMB)
Black or African American
14 Participants
n=20 Participants
Race (NIH/OMB)
White
0 Participants
n=20 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=20 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=20 Participants
Region of Enrollment
United States
14 participants
n=20 Participants

PRIMARY outcome

Timeframe: 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.

Population: 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).

Mean plasma levels obtained after e-cigarette administration at each lab session (lab 1 and lab 2).

Outcome measures

Outcome measures
Measure
Menthol Nicotine Flavor
n=8 Participants
Participants will receive 5% nicotine with menthol flavor in an e-cigarette Each exposure will be 10 3-sec puffs
Tobacco Nicotine Flavor
n=8 Participants
Participants will receive 5% nicotine with tobacco flavor in an e-cigarette Each exposure will be 10 3-sec puffs
Plasma Nicotine Levels
3.1165000 ng/mL
Standard Deviation 2.5275116
2.8126250 ng/mL
Standard Deviation 2.8678062

PRIMARY outcome

Timeframe: 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.

Population: 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.

Mean Area under the curve (AUC) for plasma nicotine and NMR were computed and then log transformed to reduce skewness of the two measures.

Outcome measures

Outcome measures
Measure
Menthol Nicotine Flavor
n=8 Participants
Participants will receive 5% nicotine with menthol flavor in an e-cigarette Each exposure will be 10 3-sec puffs
Tobacco Nicotine Flavor
n=8 Participants
Participants will receive 5% nicotine with tobacco flavor in an e-cigarette Each exposure will be 10 3-sec puffs
Nicotine Metabolic Rate
5.15 ng/mL*minutes
Standard Deviation 0.56
5.05 ng/mL*minutes
Standard Deviation 0.62

Adverse Events

Menthol Flavor

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Tobacco Flavor

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Menthol Flavor
n=14 participants at risk
Participants receiving menthol flavor
Tobacco Flavor
n=14 participants at risk
Participants receiving tobacco flavor
Cardiac disorders
High Blood Pressure
7.1%
1/14 • Number of events 1 • Participant's Adverse Event data was collected from study enrollment through both lab sessions (menthol and nicotine); approximately 3 weeks.
0.00%
0/14 • Participant's Adverse Event data was collected from study enrollment through both lab sessions (menthol and nicotine); approximately 3 weeks.
Nervous system disorders
Lightheaded
7.1%
1/14 • Number of events 1 • Participant's Adverse Event data was collected from study enrollment through both lab sessions (menthol and nicotine); approximately 3 weeks.
0.00%
0/14 • Participant's Adverse Event data was collected from study enrollment through both lab sessions (menthol and nicotine); approximately 3 weeks.

Additional Information

Thomas Liss

Yale University

Phone: 2034447545

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place