Trial Outcomes & Findings for Nicotine Flux, a Potentially Powerful Tool for Regulating Nicotine Delivery From Electronic Cigarettes (NCT NCT05706701)
NCT ID: NCT05706701
Last Updated: 2025-11-18
Results Overview
For arterial blood sampling, a radial arterial line will be placed on the non-dominant side to provide access to blood samples during vaping sessions. Blood will be sampled 30sec prior to the initial puff, 5, 15, and 25sec after each puff, and 60sec after the last puff of a bout (3 puffs per bout; 4 bouts per visit day; two visit days, separated by three weeks). The obtained data will be used to calculate pharmacokinetic parameters of nicotine delivery under each condition.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
36 participants
Primary outcome timeframe
Day 1 and Week 3
Results posted on
2025-11-18
Participant Flow
36 participants were enrolled and signed consent but 10 of those participants never started therefore 26 participants started.
Participant milestones
| Measure |
Free-base nicotine first, then protonated nicotine
Subjects will receive the free-base form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their first of two visits. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form. The same subjects from visit 1 will receive the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their second study visit.
|
Protonated nicotine first, then free-base nicotine
Subjects will receive the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their first of two visits. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form. The same subjects from visit 1 will receive the free-base form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their second study visit.
|
|---|---|---|
|
First Intervention (1 day)
STARTED
|
11
|
15
|
|
First Intervention (1 day)
9 μg/s
|
11
|
15
|
|
First Intervention (1 day)
18 μg/s
|
11
|
15
|
|
First Intervention (1 day)
27 μg/s
|
11
|
15
|
|
First Intervention (1 day)
35 μg/s
|
11
|
15
|
|
First Intervention (1 day)
COMPLETED
|
11
|
15
|
|
First Intervention (1 day)
NOT COMPLETED
|
0
|
0
|
|
Washout (3 weeks)
STARTED
|
11
|
15
|
|
Washout (3 weeks)
COMPLETED
|
6
|
12
|
|
Washout (3 weeks)
NOT COMPLETED
|
5
|
3
|
|
Second Intervention (1 day)
STARTED
|
6
|
12
|
|
Second Intervention (1 day)
9 μg/s
|
6
|
12
|
|
Second Intervention (1 day)
18 μg/s
|
6
|
12
|
|
Second Intervention (1 day)
27 μg/s
|
6
|
12
|
|
Second Intervention (1 day)
35 μg/s
|
6
|
12
|
|
Second Intervention (1 day)
COMPLETED
|
6
|
10
|
|
Second Intervention (1 day)
NOT COMPLETED
|
0
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Nicotine Flux, a Potentially Powerful Tool for Regulating Nicotine Delivery From Electronic Cigarettes
Baseline characteristics by cohort
| Measure |
Nicotine Vaping Group
n=26 Participants
Subjects will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their first of two visits. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form. The same subjects from visit 1 will receive the either free-base or protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec at their second study visit, using the opposite nicotine form that was used during the first visit.
|
|---|---|
|
Age, Continuous
|
34.69 years
STANDARD_DEVIATION 12.77 • n=39 Participants
|
|
Sex: Female, Male
Female
|
14 Participants
n=39 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
4 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
22 Participants
n=39 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Black or African American
|
5 Participants
n=39 Participants
|
|
Race (NIH/OMB)
White
|
16 Participants
n=39 Participants
|
|
Race (NIH/OMB)
More than one race
|
1 Participants
n=39 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=39 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=39 Participants
|
PRIMARY outcome
Timeframe: Day 1 and Week 3Population: Blood sample from 2 participants was unusable.
For arterial blood sampling, a radial arterial line will be placed on the non-dominant side to provide access to blood samples during vaping sessions. Blood will be sampled 30sec prior to the initial puff, 5, 15, and 25sec after each puff, and 60sec after the last puff of a bout (3 puffs per bout; 4 bouts per visit day; two visit days, separated by three weeks). The obtained data will be used to calculate pharmacokinetic parameters of nicotine delivery under each condition.
Outcome measures
| Measure |
Nicotine vaping- protonated
n=22 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=22 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Change in Maximum Arterial Blood Nicotine Delivery (Cmax)
9 μg/s
|
3.75 ng/ml
Standard Deviation 1.96
|
2.48 ng/ml
Standard Deviation 1.11
|
|
Change in Maximum Arterial Blood Nicotine Delivery (Cmax)
18 μg/s
|
8.12 ng/ml
Standard Deviation 4.81
|
2.96 ng/ml
Standard Deviation 1.76
|
|
Change in Maximum Arterial Blood Nicotine Delivery (Cmax)
27 μg/s
|
13.23 ng/ml
Standard Deviation 7.7
|
5.13 ng/ml
Standard Deviation 3.16
|
|
Change in Maximum Arterial Blood Nicotine Delivery (Cmax)
35 μg/s
|
18.57 ng/ml
Standard Deviation 12.19
|
6.11 ng/ml
Standard Deviation 3.55
|
SECONDARY outcome
Timeframe: Day 1 and Week 3AUC from 0 to 160min for the four 3-puff directed bouts will be estimated using a non-compartmental model and trapezoidal rule. The four 3-puff directed bouts occur on both visit day 1 and 2, separated by 3 weeks. All measures will be corrected for baseline values by subtracting the blood nicotine concentrations by the initial value (at the start of each bout).
Outcome measures
| Measure |
Nicotine vaping- protonated
n=22 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=22 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Change in Area Under the Curve for Nicotine (AUC)
35 μg/s
|
1499.38 (ng/ml)*s
Standard Deviation 1017.08
|
571.53 (ng/ml)*s
Standard Deviation 317.55
|
|
Change in Area Under the Curve for Nicotine (AUC)
27 μg/s
|
1022.42 (ng/ml)*s
Standard Deviation 573.32
|
443.79 (ng/ml)*s
Standard Deviation 231.72
|
|
Change in Area Under the Curve for Nicotine (AUC)
9 μg/s
|
316.06 (ng/ml)*s
Standard Deviation 196.91
|
225.68 (ng/ml)*s
Standard Deviation 133.22
|
|
Change in Area Under the Curve for Nicotine (AUC)
18 μg/s
|
643.48 (ng/ml)*s
Standard Deviation 431.98
|
255.38 (ng/ml)*s
Standard Deviation 164.15
|
SECONDARY outcome
Timeframe: Day 1 and Week 3Population: Data presented here is for all participants that completed the assessment.
Determined by ENDS gravimetric weight change. Pre- and Post- vaping on both visit day 1 and 2, separated by 3 weeks.
Outcome measures
| Measure |
Nicotine vaping- protonated
n=11 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=11 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Change in Liquid Consumed
9 μg/s
|
0.08 grams
Standard Deviation 0.06
|
0.08 grams
Standard Deviation 0.13
|
|
Change in Liquid Consumed
18 μg/s
|
0.02 grams
Standard Deviation 0.01
|
0.09 grams
Standard Deviation 0.07
|
|
Change in Liquid Consumed
27 μg/s
|
0.03 grams
Standard Deviation 0.01
|
0.09 grams
Standard Deviation 0.12
|
|
Change in Liquid Consumed
35 μg/s
|
0.05 grams
Standard Deviation 0.03
|
0.08 grams
Standard Deviation 0.10
|
SECONDARY outcome
Timeframe: Day 1 and Week 3Average puff duration in seconds for 3 puffs on both visit day 1 and 2, separated by 3 weeks. Data presented here is the average duration per condition.
Outcome measures
| Measure |
Nicotine vaping- protonated
n=24 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=24 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Mean Change in Puff Topography
9 μg/s
|
2.81 seconds
Standard Deviation 1.18
|
2.78 seconds
Standard Deviation 1.10
|
|
Mean Change in Puff Topography
18 μg/s
|
2.81 seconds
Standard Deviation 1.22
|
2.66 seconds
Standard Deviation 1.16
|
|
Mean Change in Puff Topography
27 μg/s
|
2.83 seconds
Standard Deviation 1.25
|
2.3 seconds
Standard Deviation 1.24
|
|
Mean Change in Puff Topography
35 μg/s
|
2.8 seconds
Standard Deviation 1.23
|
2.2 seconds
Standard Deviation 1.22
|
SECONDARY outcome
Timeframe: Day 1 and Week 3Blood will be sampled 30sec prior to the initial puff, 5, 15, and 25sec after each puff, and 60sec after the last puff of a bout. Measurements occur 4 times per visit day, on both visit day 1 and 2, separated by 3 weeks). The obtained data will be used to calculate pharmacokinetic parameters of nicotine delivery under each condition (dCi/dt).
Outcome measures
| Measure |
Nicotine vaping- protonated
n=22 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=22 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)
9 μg/s
|
0.12 ng/(ml*s)
Standard Deviation 0.11
|
0.09 ng/(ml*s)
Standard Deviation 0.07
|
|
Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)
18 μg/s
|
0.28 ng/(ml*s)
Standard Deviation 0.22
|
0.08 ng/(ml*s)
Standard Deviation 0.06
|
|
Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)
27 μg/s
|
0.44 ng/(ml*s)
Standard Deviation 0.34
|
0.13 ng/(ml*s)
Standard Deviation 0.09
|
|
Change in Rate of Nicotine Rise After the Initial Puff (dCi/dt)
35 μg/s
|
0.57 ng/(ml*s)
Standard Deviation 0.42
|
0.18 ng/(ml*s)
Standard Deviation 0.13
|
SECONDARY outcome
Timeframe: Day 1 and Week 3Blood will be sampled 30sec prior to the initial puff, 5, 15, and 25sec after each puff, and 60sec after the last puff of a bout. Measurements occur 4 times per visit day, on both visit day 1 and 2, separated by 3 weeks). The obtained data will be used to calculate pharmacokinetic parameters of nicotine delivery under each condition (Tmax).
Outcome measures
| Measure |
Nicotine vaping- protonated
n=22 Participants
Subjects received the protonated form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
Nicotine vaping- freebase
n=22 Participants
Subjects received the freebase form of four nicotine fluxes: 9, 18, 27, 35 μg/sec. In the first visit, participants will use the ENDS device with one nicotine form and four fluxes in random order. Participants will be instructed to attend the lab for a second visit, to test the four fluxes but with the other nicotine form.
|
|---|---|---|
|
Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)
35 μg/s
|
100 seconds
Standard Deviation 28.69
|
109.44 seconds
Standard Deviation 24.10
|
|
Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)
9 μg/s
|
93.83 seconds
Standard Deviation 45.33
|
102.88 seconds
Standard Deviation 42.4
|
|
Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)
18 μg/s
|
100.32 seconds
Standard Deviation 27.85
|
99.81 seconds
Standard Deviation 32.44
|
|
Change in Time to Maximum Arterial Blood Level Nicotine Concentration (Tmax)
27 μg/s
|
99 seconds
Standard Deviation 34.56
|
106.31 seconds
Standard Deviation 23.24
|
Adverse Events
Free-base nicotine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Protonated nicotine
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Arterial-line related
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Between visits
Serious events: 1 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Free-base nicotine
n=26 participants at risk
Subject received free-base nicotine
|
Protonated nicotine
n=26 participants at risk
Subject received protonated nicotine
|
Arterial-line related
n=26 participants at risk
Adverse event occurred due to arterial-line placement prior to intervention and unrelated to the interventions
|
Between visits
n=26 participants at risk
Adverse event occurred between visits and unrelated to the interventions
|
|---|---|---|---|---|
|
Injury, poisoning and procedural complications
Self harm episode
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
3.8%
1/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
Other adverse events
| Measure |
Free-base nicotine
n=26 participants at risk
Subject received free-base nicotine
|
Protonated nicotine
n=26 participants at risk
Subject received protonated nicotine
|
Arterial-line related
n=26 participants at risk
Adverse event occurred due to arterial-line placement prior to intervention and unrelated to the interventions
|
Between visits
n=26 participants at risk
Adverse event occurred between visits and unrelated to the interventions
|
|---|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
3.8%
1/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
|
Musculoskeletal and connective tissue disorders
Wrist discomfort
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
19.2%
5/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
|
Cardiac disorders
Pre-syncope
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
3.8%
1/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
|
Cardiac disorders
Arterial vasospasm
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
3.8%
1/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
0.00%
0/26 • 3 weeks
The one serious adverse event occurred while the participant was between study visits and not treatment related. Each nicotine flux was given sequentially at each visit therefore adverse events can only be reported for the assigned interventions: Free-base vs Protonated nicotine.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place