Trial Outcomes & Findings for Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study (NCT NCT02783768)
NCT ID: NCT02783768
Last Updated: 2020-10-22
Results Overview
PMBF will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures. There were four days between the measurements of PMBF (e-cigarette) and PMBF (sham). PMBF is measured in mL(blood)/min/mL(lung volume). Lower PMBF has been observed in adults with COPD and emphysema.
COMPLETED
EARLY_PHASE1
12 participants
After exposure (approximately 30 seconds)
2020-10-22
Participant Flow
There were a total of 12 subjects enrolled. 6 subjects were randomized to "E-cigarette first," of which 5 completed the full protocol. 5 subjects were randomized to "Sham first," all 5 of whom completed the full protocol. 1 subject was consented but not randomized.
Participant milestones
| Measure |
E-cigarette First
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
|
Sham First
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
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|---|---|---|
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Overall Study
STARTED
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6
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5
|
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Overall Study
COMPLETED
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5
|
5
|
|
Overall Study
NOT COMPLETED
|
1
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0
|
Reasons for withdrawal
| Measure |
E-cigarette First
Participants will undergo the e-cigarette exposure prior to the first two MRI measures, and then they will undergo the sham exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
|
Sham First
Participants will undergo the sham exposure prior to the first two MRI measures, and then they will undergo the e-cigarette exposure prior to the last two MRI measures. The two MRIs performed under both experimental exposures (e-cigarette and sham) will be enhanced by (1) gadolinium and then (2) hyperpolarized 3-helium.
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|---|---|---|
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Overall Study
Lost to Follow-up
|
1
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0
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Baseline Characteristics
Ventilation and Pulmonary Endothelium Toxicities of E-cigarettes: A Randomized Crossover Pilot Study
Baseline characteristics by cohort
| Measure |
Total
n=11 Participants
This is a randomized crossover study. Participants were randomized to two groups, which differed by order of the exposure to e-cigarette versus sham: (1) e-cigarette first, followed by sham, or (2) sham first, followed by e-cigarette. All participants were both "exposed" and "unexposed."
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|---|---|
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Age, Categorical
<=18 years
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0 Participants
n=93 Participants
|
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Age, Categorical
Between 18 and 65 years
|
11 Participants
n=93 Participants
|
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Age, Categorical
>=65 years
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0 Participants
n=93 Participants
|
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Sex: Female, Male
Female
|
0 Participants
n=93 Participants
|
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Sex: Female, Male
Male
|
11 Participants
n=93 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
6 Participants
n=93 Participants
|
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Ethnicity (NIH/OMB)
Not Hispanic or Latino
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5 Participants
n=93 Participants
|
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Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
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Race (NIH/OMB)
American Indian or Alaska Native
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0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Asian
|
2 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=93 Participants
|
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Race (NIH/OMB)
Black or African American
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2 Participants
n=93 Participants
|
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Race (NIH/OMB)
White
|
1 Participants
n=93 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=93 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
6 Participants
n=93 Participants
|
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Region of Enrollment
United States
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11 participants
n=93 Participants
|
PRIMARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) experienced both e-cigarette and sham exposures. In this outcome measure, the same 10 evaluable subjects all had exposure and no exposure at different time periods in the study.
PMBF will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures. There were four days between the measurements of PMBF (e-cigarette) and PMBF (sham). PMBF is measured in mL(blood)/min/mL(lung volume). Lower PMBF has been observed in adults with COPD and emphysema.
Outcome measures
| Measure |
Exposed to E-cigarette
n=10 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=10 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Pulmonary Microvascular Blood Flow (PMBF), Measured on Gadolinium-enhanced MRI, Between E-cigarette Exposed and Unexposed Conditions
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74.4 mL(blood)/min/mL(lung)
Standard Deviation 23.9
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63.1 mL(blood)/min/mL(lung)
Standard Deviation 19.4
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PRIMARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: A subset of participants were unable to complete the 3-He enhanced MRI due to problems with the helium polarizer and/or scanner (e.g., unable to fit into scanner due to body size). In this outcome measure, 7 out of 11 subjects had evaluable data.
VDP will be measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures. Due to limitations of prior qualitative/visual assessments of MRI, we developed and validated a new deep learning approach to the precise measurement of ventilation defects and report the percent non-fully ventilated lung using this method.
Outcome measures
| Measure |
Exposed to E-cigarette
n=7 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=7 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Ventilation Defect Percentage (VDP), Measured on Hyperpolarized 3-helium Enhanced MRI
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5.5 percentage of total lung volume
Standard Deviation 4.4
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6.6 percentage of total lung volume
Standard Deviation 4.4
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SECONDARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: Data were not analyzed due to unavailable resources and technology because of the pandemic.
Regional PMBF (ie, in the right versus left, upper versus lower lobes) will be measured on gadolinium-enhanced MRI after e-cigarette and sham exposures.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: A subset of participants were unable to complete the 3-He enhanced MRI due to problems with the helium polarizer and/or scanner (e.g., unable to fit into scanner due to body size). In this outcome measure, 7 out of 11 subjects had evaluable data.
Regional VDP in the lower lung was measured on hyperpolarized 3Helium-enhanced MRI after e-cigarette and sham exposures.
Outcome measures
| Measure |
Exposed to E-cigarette
n=7 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=7 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Regional VDP, Measured on Hyperpolarized 3-helium Enhanced MRI
|
3.6 percentage of total lung volume
Standard Deviation 2.8
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5.8 percentage of total lung volume
Standard Deviation 6.2
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SECONDARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: In this outcome measure, 7 out of 11 subjects had evaluable data.
Lung function will be measured on spirometry. Two participants had only one valid FEV1 measure, and one participant had no valid FEV1 measures. Hence, 3 participants (2 in "E-cigarette first" and 1 in "Sham first") were not analyzed. The analysis combines the groups in order to separate the effects of randomization group (order) and exposure.
Outcome measures
| Measure |
Exposed to E-cigarette
n=7 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=7 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Lung Function, Measured on Spirometry
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4.22 L
Standard Deviation 0.75
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4.08 L
Standard Deviation 1.14
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SECONDARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: In this outcome measure, the machine broke and only 3 subjects had evaluable data for the exposed time period and 2 subjects had evaluable data for the unexposed time period
DLCO will be measured. There was a malfunction of the machine used to measure the DLCO. Hence, only one participant had paired DLCO values and 3 had unpaired measures.
Outcome measures
| Measure |
Exposed to E-cigarette
n=3 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=2 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
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33.65 mL/min/mm Hg
Standard Deviation 3.53
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32.73 mL/min/mm Hg
Standard Deviation 8.69
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SECONDARY outcome
Timeframe: After exposure (approximately 30 seconds)Population: In this outcome measure, 8 subjects had evaluable data for the exposed time period and 7 subjects had evaluable data for the unexposed time period.
Cardiac output will be measured on cardiac MRI. In the "E-cigarette first" arm, 2 participants did not have 2 valid measures of CO (one pair was missing, one was invalid). In the "Sham first" arm, 3 participants had one invalid measure of CO. The analysis combines the groups in order to separate the effects of randomization group (order) and exposure.
Outcome measures
| Measure |
Exposed to E-cigarette
n=8 Participants
Participants were exposed to a standardized e-cigarette prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
|
Unexposed (Sham)
n=7 Participants
Participants were exposed to a standardized sham prior to MRI measurement of the outcome measure. Since this study applied a randomized crossover design, participants from both randomization groups (exposure first and sham first) are reported in this group.
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|---|---|---|
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Cardiac Output, Measured on Cardiac MRI
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6197 mL/min
Standard Deviation 1097
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6093 mL/min
Standard Deviation 844
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Adverse Events
E-cigarette First
Sham First
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place