Tobacco UseNCT03863509
E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease
An observational study of Tobacco Use and E-Cigarette Use, run by University of Wisconsin, Madison at 1 site in United States.
Trial summary
This study is designed to enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tobacco Use, E-Cigarette Use, Cardiovascular Diseases
- What is being tested?
- Cigarettes and E-Cigarettes
- Type of treatment
- Lifestyle or therapy programme
- How many people
- 450 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Mar 2019to 9 Mar 2022
- Phase
- Observational
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: 165 exclusive E-cig users, 165 exclusive cigarette smokers, and 110 never-users will be enrolled. Tobacco product use will be examined via time-line follow-back use-history measures, real-time measures, and lab measures. Potential participants will be assessed for eligibility via a phone screen. Because biomarker status may be affected by age and sex, groups will be stratified equally for gender (48/52 male/female) and age (≤35/>35 years).
Who may be able to join
- able to read and write English
- no plans to quit smoking and/or e-cig use in the next month
- not using cigars/smokeless/snus tobacco >/= 1 time per week
- having a stable pattern of current product use
- able to walk at least 2 blocks without assistance or stopping
- Specific to Exclusive Smokers:
Show all 21Show fewer
- smokes daily
- >/= 5 cigs/day for last 6 months
- < 3 uses E-cigs in lifetime
- >/= 5 ppm carbon monoxide (CO)
- Cotinine > 100 ng/ml
- Specific to Exclusive E-cig users:
- </= 2 days per month cigarette use for last 6 months
- >/= 5 days per week E-cig use for last 3 months
- </= 4 ppm CO
- Cotinine > 100 ng/ml
- Specific to Never-users
- < 100 cigarettes in a lifetime, none for > 5 years
- < 3 E-cig uses in a lifetime
- </= 4 ppm CO
- Cotinine < 100 ng/ml
Who cannot join
- current use of a smoking cessation medication
- women who are pregnant or plan to get pregnant in the coming month
- women who might be pregnant
- incarcerated individuals
- history of sarcoidosis in past 5 years, or active interstitial lung/pulmonary fibrosis
- history of positive Coronavirus-19 test
Trial locations and contacts
1 site in 1 country.
About this study
Official title: E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease Risk (Aka CLUES - Cardiac and Lung E-cig Smoking Study)
This study is designed to enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. Participants will be enrolled in 3 groups: exclusive e-cigarette users, exclusive cigarette smokers, and a control group of never-users. Participants can expect up to 4 weeks of study participation.
Read the detailed description
E-cigarette use is increasing rapidly in the United States, especially amongst youth, underscoring the vital need to improve understanding of its health risks. Relevant data could inform policy, guide public health and clinical intervention efforts, and inform individuals who might use or who are using this product. This research will significantly enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. 3 different "use-groups" of participants will be enrolled: exclusive e-cigarette users (n=165), exclusive cigarette smokers (n=165), and a "control" group of never-users (n=110). These groups reflect the primary decisions that people can make regarding their future tobacco use: to continue to smoke cigarettes, to switch to e-cigarettes, or to avoid tobacco use entirely. It is essential that smokers and health care providers have accurate information on the health effect of these choices.
[Additionally, 100 participants will be invited to be part of an epigenetics sub-study (50 E-cig users, 25 smokers and 25 controls), prior to smoking, an additional 16 ml of blood will be collected in Vacutainer cell separation tubes for peripheral blood monocyte (PBMC) Isolation containing sodium citrate.]
Product use will be related to well-validated biomarkers that sensitively and reproducibly reflect mechanisms, injury, and/or future risk related to cardiovascular or pulmonary disease. Biomarkers will be related to: 1) acute product use in the laboratory (exposure challenges), 2) lifetime history of product use, and/or 3) real-time measures of product use in participants' daily lives. The primary cardiovascular biomarkers are brachial artery flow-mediated dilation (a measure of endothelial function) and carotid intima-media thickness, a measure of subclinical arterial injury and atherosclerosis. The primary pulmonary disease biomarkers will be measures of lung volumes and flow rates (Forced Expiatory Volume exhaled in the first second (FEV1), Forced vital capacity (FVC), FEV1/FVC) obtained by spirometry. Treadmill exercise stress testing will be performed (to assess aerobic fitness), electrocardiography (to measure heart rate variability, HRV), and measure heart rate, blood pressure, lipids, HgbA1c, and inflammation/oxidation markers (leukocyte count, C-reactive protein, urinary F2 isoprostanes and exhaled nitric oxide). This research will show how product use-groups differ in response to acute product use and long-term use as they are related to key cardiovascular and pulmonary biomarkers. Objective measures of product use include exhaled CO and plasma nicotine/cotinine and urinary nicotine/cotinine concentrations. History of product use within use-groups will be related to biomarker status.
The proposed research will yield vital and comprehensive data regarding product use, subclinical arterial injury, atherosclerosis burden, arterial and pulmonary function, cardiac and aerobic fitness, cardiac autonomic regulation, systemic and pulmonary inflammation, and oxidative stress, as well as other key outcomes. These data will serve as a foundation for future longitudinal investigations of e-cigarette health effects and will inform public policy decisions, clinical intervention, and patient guidance regarding e-cigarettes.
- Being tested
- Cigarettes, E-Cigarettes
- Keywords
- vape, E-Cigarette, E-cig
- Medical subject headings
- Tobacco Use, Vaping, Cardiovascular Diseases, Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CigarettesBehavioural
smokes daily
E-CigarettesBehavioural
Also called E-cig, Vape
E-cigarette usage >/= 5 days/week
| Study group | Role | What they receive |
|---|---|---|
| Exclusive Smokers | Smokes Daily; >/= 5 cigarettes/day for last 6 months Receives: Behavioral: Cigarettes | |
| Exclusive E-Cig users | E-cig usage >/= 5 days/week for last 3 months Receives: Behavioral: E-Cigarettes | |
| Never users | < 100 cigarettes in lifetime, none for > 5 years; < 3 E-cig usage in lifetime |
What is being measured
The primary outcome is the main question the study is designed to answer.
Brachial Artery Flow-Mediated Dilation (FMD)- Pre Challenge
Brachial Artery Flow-Mediated Dilation is a primary cardiovascular biomarker and a measure of endothelial function that will be assessed before and after an acute exposure challenge. These are pre-challenge values.
Ultrasound based changes in brachial artery diameter after a forearm cuff occlusion (250mmHg) for 5 minutes. FMD is the percent change in brachial diameter measured 60 to 90 seconds post cuff release compared to its resting diameter. A higher % dilation is an indication of better endothelial function.
Measured: V2 up to 4 weeks from enrollment visit, fasting
Forced Expiratory Volume (FEV1)- Pre Challenge
FEV1 is a primary measure of pulmonary disease obtained by spirometry that will be assessed before and after an acute exposure challenge. These are per-challenge values
Measured: V2 up to 4 weeks from enrollment visit , fasting, pre challenge session
Carotid Intima-Media Thickness (IMT)
Carotid Intima-Media Thickness is a cardiovascular biomarker and a measure of sub-clinical arterial injury and atherosclerosis as a result of chronic exposure. IMT will be measured via ultrasonography.
Measured: V2 up to 4 weeks from enrollment visit, only done pre-challenge
Changes in Systolic Blood Pressure Pre- and Post-challenge.
Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting.. They came in the morning after 8 hours of fasting and refraining from nicotine products. Systolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.
Measured: During Visit 2 (1 - 4 weeks post enrollment) before and after smoking/vaping challenge and for controls after a 10 minute break
Changes in Diastolic Blood Pressure Pre- and Post-challenge.
Participants returned for V2 up to 4 weeks from enrollment visit, fasting. They came in the morning after 8 hours of fasting and refraining from nicotine products. Diastolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.
Measured: before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Changes in Heart Rate Pre- and Post-challenge.
Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge heart rate measured supine, after 10 minutes rest from blood pressure monitor (dinamap). The post challenge heart rates were recorded 15-20 minutes post end of exposure to smoking or vaping challenge completion or in the case of controls after a 10 minute break.
Measured: Before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Changes in Brachial Artery Diameter Pre- and Post-challenge
Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break.
Measured: before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Changes in Brachial Artery Flow Mediated Dilation (FMD) Pre- and Post-challenge
Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge ultrasound of brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break. The FMD protocol includes measuring % change in resting diameter after 60-90 seconds post fore-arm cuff occlusion release.
Measured: Testing was done after 10 minutes rest and fasting for pre- and post-challenge. The post challenge FMD were recorded 15-20 minuted after end of exposure (up to 4 weeks from enrollment)
Changes in Percent of Sequential Heart Cycles That Differ by More Than 50 ms From Each Other in Length (PNN50, %) Pre- and Post-challenge
Expressed as a percentage of beats (supine recordings had be 5 minutes or longer to be valid). We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 1-2 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break.
Measured: During V2 (scheduled up to 4 weeks from enrollment) and obtained after 10 minutes of supine rest, before and after smoking/vaping challenge
Changes in Root Mean Square of Successive Differences Between Normal Heart Beats (RMSSD, ms) Pre- and Post-challenge
Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls it was repeated after a 10 minute break.
Measured: heart rate variability recordings of at least 10 minutes per-challenge and 15 minutes post-challenge (up to 4 weeks from enrollment)
Changes in Heart Rate Variability Standing Ratio Pre- and Postchallenge
We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability standing ratio was assessed pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break. Ratio between maximal heart rate after abrupt standing from a supine position and the subsequent lowest heart rate value within 40 seconds of peak.
Measured: Ratio was measured pre- and post- smoking/vaping challenge after completion of the 10 minutes of heart rate variability measures (up to 4 weeks from enrollment)
Changes in Predicted Forced Expiatory Volume in 1 Second (FEV1, %) Pre- and Post-challenge
maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation, expressed as a percentage of the predicted normal values in the population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Measured: before and after smoking/vaping challenge during Visit 2 (1-4 weeks after enrollment visit)
Changes in Forced Vital Capacity (FVC, %) Pre- and Post-Challenge.
Amount of air that can be forcibly exhaled after taking the deepest breath possible expressed as a predicted percentage from the normal population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Measured: before and after smoking/vaping challenge during Visit 2 Visit 2 which was scheduled 1 to 4 weeks from enrollment visit, fasting
Changes in Ratio Between Predicted Forced Expiatory Volume in First Second and Predicted Total Vital Capacity (FEV1/FVC Ratio) Pre- and Post-challenge
The post challenge spirometry was recorded <15 minutes post end of exposure. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Measured: before and after smoking/vaping challenge during Visit 2 (1-4 weeks after enrollment visit)
Changes in Percent Predicted Forced Expiratory Flow at 25 and 75% of the Pulmonary Volume (FEF 25-75, %) Pre and Pos-challenge
Participants attended Visit 2 (1-4 weeks after enrollment visit). They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Measured: Spirometry performed pre-challenge and within 15 minutes post-challenge (up to 4 weeks from enrollment)
Changes in Fractional Exhaled Nitric Oxide (FeNO, Ppb) Pre- and Post-challenge
Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge FeNO was obtained sitting and repeated within 15 minutes after smoking/vaping challenge.
Measured: before and after less than 15 minutes from smoking/ vaping product (up to 4 weeks from enrollment)
Secondary outcomes (12)
Heart Rate (HR)
Heart Rate pre-acute exposure challenge was obtained after resting supine for 10 minutes during V2 in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior.
Measured: Participants attended V2 generally 1-4 weeks after enrollment with a window that allowed up to 4 weeks after enrollment
Heart Rate Variability (HRV) - Pre Product Use Challenge
Heart Rate Variability PNN50(%) measured before an exposure challenge. Participants attended visit 2 fasting and refraining from nicotine for at least 8 hours.
Measured: V2 two was generally scheduled 1-4 weeks after enrollment visit with a window up to 4 weeks. HRV measures obtained after resting supine for 10 minutes
Systolic Blood Pressure (BP)
Blood Pressure measured using the oscillometric technique before an acute exposure challenge following standardized protocol. After resting supine for 10 minutes blood pressure was measured on both arms and the average of the last two values was used.
Measured: V2 was up to 4 weeks from enrollment visit, after resting supine for 10 minutes
Forced Vital Capacity (FVC)
Forced Vital Capacity is a measure of how much air can be exhaled forcefully obtained by spirometry pre acute exposure challenge.
Measured: recordings obtained during V2 in the morning, fasting and refraining from nicotine for at least 8 hours. This visit was generally 1-2 weeks after enrollment date with a window up to 4 weeks
Fractional Exhaled Nitric Oxide (FeNO)
Fractional Exhaled Nitric Oxide is a measure of airway inflammation measured before an acute exposure challenge.
Measured: recordings obtained during V2 in the morning, fasting and refraining from nicotine for at least 8 hours. This visit was generally 1-2 weeks after enrollment date with a window up to 4 weeks
Autonomic Measures - RMSSD
Root mean square of standard deviation of rr intervals. Obtained fasting and refraining from nicotine exposure using the Sphymocor system. We used 10 or more minutes of supine data to derive heart rate variability measures.
Measured: v2 was generally 1-2 weeks after enrollment visit, with a window up to 4 weeks from V1
Arterial Pulse Wave Analysis (PWA), Augmentation Index (at 75 Bpm, %)
Analysis of radial pressure wave forms allows for non-invasive estimation of central aortic pressures, accounting for pressure amplification and the amplitude of the arterial pulse wave as it moves through arteries away from the heart. The Atcor Sphygmacor system can derive central aortic pressures from radial tracings using a validated transfer function. This computation is performed using the pulse wave analysis (PWA) mode. Pulse Wave Analysis via radial tonometry was obtained as a measure of chronic exposure.
Measured: v2 was generally 1-2 weeks after enrollment visit, with a window up to 4 weeks from V1
Exercise Treadmill Stress Test (ETT)-Peak METS
An ETT to determine exercise capacity will be completed as a measure of chronic exposure. Peak metabolic equivalents (METs, 1 MET=3.5 ml O2 uptake/kg body weight/minute) were determined at all exercise stages, peak exercise, and 1-minute post-exercise.
Measured: Treadmill test done only once at the end of v2 after completion of all other post-challenge assessment tests. V2 was scheduled 1-4 weeks from enrollment vist
Diastolic Blood Pressure (DBP)
During V2, Diastolic Blood Pressure was measured using the oscillometric technique before an acute exposure challenge following a standardized protocol. After resting supine for 10 minutes blood pressure was measured on both arms and the average of the last two values was used. Participants attended v2 in the morning, fasting and refraining from nicotine products for at least 8 hours.
Measured: V2 was generally 1-2 weeks after enrollment with a window up to 4 weeks from V1, recorded after resting supine for 10 minutes
Peak Rate Pressure Product (RPP, Peak Heart Rate Multiplied by Peak Systolic Blood Pressure)
Peak RPP was calculated by multiplying maximun heart rate during exercise by systolic blood pressure as a reliable assessment of cardiac workload
Measured: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or pretend 10 minute exposure for controls
Heart Rate Reserve (%)
Measure of maximal exercise capacity adjusted for age, calculated as max heart rate during treadmill divided by (220 minus the participant's age in yrs)
Measured: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or 10 minute pretend exposure for never-users
60 Seconds Heart Rate Recovery (Beats Per Minute)
Difference in heart rate 60 seconds post treadmill minus maximal heart rate during treadmill..
Measured: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or pretend 10 minute exposure for controls
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start5 Mar 2019
- Primary completion9 Mar 2022
- Study completion9 Mar 2022
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Tobacco UseStudies of the same condition, open and under way.
- More trials run by University of Wisconsin, MadisonThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Wisconsin, Madison
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor
- Investigators
- James H Stein, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03863509
- Sponsor's protocol ID
- 2017-1090
- Other IDs
- 1R01HL139331-01, Protocol Version 4/26/2021, A534225, SMPH\MEDICINE\CARDIOLOGY
- Status last verified
- Aug 2023
- First submitted
- 28 Feb 2019
- Last updated
- 21 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Our plan includes the creation of a data archive with coded information in computer-readable form for distribution to the scientific community using the procedures outlined below. The information will include a codebook with definitions of variables, variable field locations, summary statistics and any standard scoring. Final data sets will be stripped of identifiers prior to release for sharing (the release of a limited data set containing one or more specific identifiers would be considered if absolutely required by the researcher and if the request meets all University of Wisconsin -Institutional Review Board and Office of Human Research Protections policies. We will make all key variables available via posting of final data codebook and dataset in suitable archives. All shared variables and datasets will be de-identified and approved for sharing by the University of Wisconsin and Institutional Review Board
Publications
Tattersall MC, Hughey CM, Piasecki TM, Korcarz CE, Hansen KM, Ott NR, Sandbo N, Fiore MC, Baker TB, Stein JH. Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users. Chest. 2023 Sep;164(3):757-769. doi: 10.1016/j.chest.2023.03.047. Epub 2023 Apr 10.
PubMed 37044158
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease Risk (Aka CLUES - Cardiac and Lung E-cig Smoking Study)
- ClinicalTrials.gov ID
- NCT03863509
- Acronym / sponsor ID
- 2017-1090
- Keywords
- vape, E-Cigarette, E-cig
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 450 participants (actual)
- Lead sponsor
- University of Wisconsin, MadisonUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 5 Mar 2019 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Posted 21 Aug 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. Participants will be enrolled in 3 groups: exclusive e-cigarette users, exclusive cigarette smokers, and a control group of never-users. Participants can expect up to 4 weeks of study participation.
Detailed description
E-cigarette use is increasing rapidly in the United States, especially amongst youth, underscoring the vital need to improve understanding of its health risks. Relevant data could inform policy, guide public health and clinical intervention efforts, and inform individuals who might use or who are using this product. This research will significantly enhance the understanding of the possible health effects of e-cigarette use by relating the acute and long-term use of e-cigarettes and conventional cigarettes ("products") to well-validated cardiovascular and pulmonary disease biomarkers. 3 different "use-groups" of participants will be enrolled: exclusive e-cigarette users (n=165), exclusive cigarette smokers (n=165), and a "control" group of never-users (n=110). These groups reflect the primary decisions that people can make regarding their future tobacco use: to continue to smoke cigarettes, to switch to e-cigarettes, or to avoid tobacco use entirely. It is essential that smokers and health care providers have accurate information on the health effect of these choices.
[Additionally, 100 participants will be invited to be part of an epigenetics sub-study (50 E-cig users, 25 smokers and 25 controls), prior to smoking, an additional 16 ml of blood will be collected in Vacutainer cell separation tubes for peripheral blood monocyte (PBMC) Isolation containing sodium citrate.]
Product use will be related to well-validated biomarkers that sensitively and reproducibly reflect mechanisms, injury, and/or future risk related to cardiovascular or pulmonary disease. Biomarkers will be related to: 1) acute product use in the laboratory (exposure challenges), 2) lifetime history of product use, and/or 3) real-time measures of product use in participants' daily lives. The primary cardiovascular biomarkers are brachial artery flow-mediated dilation (a measure of endothelial function) and carotid intima-media thickness, a measure of subclinical arterial injury and atherosclerosis. The primary pulmonary disease biomarkers will be measures of lung volumes and flow rates (Forced Expiatory Volume exhaled in the first second (FEV1), Forced vital capacity (FVC), FEV1/FVC) obtained by spirometry. Treadmill exercise stress testing will be performed (to assess aerobic fitness), electrocardiography (to measure heart rate variability, HRV), and measure heart rate, blood pressure, lipids, HgbA1c, and inflammation/oxidation markers (leukocyte count, C-reactive protein, urinary F2 isoprostanes and exhaled nitric oxide). This research will show how product use-groups differ in response to acute product use and long-term use as they are related to key cardiovascular and pulmonary biomarkers. Objective measures of product use include exhaled CO and plasma nicotine/cotinine and urinary nicotine/cotinine concentrations. History of product use within use-groups will be related to biomarker status.
The proposed research will yield vital and comprehensive data regarding product use, subclinical arterial injury, atherosclerosis burden, arterial and pulmonary function, cardiac and aerobic fitness, cardiac autonomic regulation, systemic and pulmonary inflammation, and oxidative stress, as well as other key outcomes. These data will serve as a foundation for future longitudinal investigations of e-cigarette health effects and will inform public policy decisions, clinical intervention, and patient guidance regarding e-cigarettes.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Exclusive Smokers | – | Behavioral: CigarettesSmokes Daily; >/= 5 cigarettes/day for last 6 months |
| Exclusive E-Cig users | – | Behavioral: E-CigarettesE-cig usage >/= 5 days/week for last 3 months |
| Never users | – | –< 100 cigarettes in lifetime, none for > 5 years; < 3 E-cig usage in lifetime |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- 165 exclusive E-cig users, 165 exclusive cigarette smokers, and 110 never-users will be enrolled. Tobacco product use will be examined via time-line follow-back use-history measures, real-time measures, and lab measures. Potential participants will be assessed for eligibility via a phone screen. Because biomarker status may be affected by age and sex, groups will be stratified equally for gender (48/52 male/female) and age (≤35/>35 years).
Key inclusion criteria (21 listed)
- able to read and write English
- no plans to quit smoking and/or e-cig use in the next month
- not using cigars/smokeless/snus tobacco >/= 1 time per week
- having a stable pattern of current product use
- able to walk at least 2 blocks without assistance or stopping
Key exclusion criteria (6 listed)
- current use of a smoking cessation medication
- women who are pregnant or plan to get pregnant in the coming month
- women who might be pregnant
- incarcerated individuals
- history of sarcoidosis in past 5 years, or active interstitial lung/pulmonary fibrosis
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 |
|---|---|---|
| Cigarettessmokes daily | Behavioural | Exclusive Smokers |
| E-CigarettesAlso: E-cig, VapeE-cigarette usage >/= 5 days/week | Behavioural | Exclusive E-Cig users |
Primary outcome
Brachial Artery Flow-Mediated Dilation (FMD)- Pre Challenge
Time frame: V2 up to 4 weeks from enrollment visit, fasting
Brachial Artery Flow-Mediated Dilation is a primary cardiovascular biomarker and a measure of endothelial function that will be assessed before and after an acute exposure challenge. These are pre-challenge values. Ultrasound based changes in brachial artery diameter after a forearm cuff occlusion (250mmHg) for 5 minutes. FMD is the percent change in brachial diameter measured 60 to 90 seconds post cuff release compared to its resting diameter. A higher % dilation is an indication of better endothelial function.
Forced Expiratory Volume (FEV1)- Pre Challenge
Time frame: V2 up to 4 weeks from enrollment visit , fasting, pre challenge session
FEV1 is a primary measure of pulmonary disease obtained by spirometry that will be assessed before and after an acute exposure challenge. These are per-challenge values
Carotid Intima-Media Thickness (IMT)
Time frame: V2 up to 4 weeks from enrollment visit, only done pre-challenge
Carotid Intima-Media Thickness is a cardiovascular biomarker and a measure of sub-clinical arterial injury and atherosclerosis as a result of chronic exposure. IMT will be measured via ultrasonography.
Changes in Systolic Blood Pressure Pre- and Post-challenge.
Time frame: During Visit 2 (1 - 4 weeks post enrollment) before and after smoking/vaping challenge and for controls after a 10 minute break
Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting.. They came in the morning after 8 hours of fasting and refraining from nicotine products. Systolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.
Changes in Diastolic Blood Pressure Pre- and Post-challenge.
Time frame: before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Participants returned for V2 up to 4 weeks from enrollment visit, fasting. They came in the morning after 8 hours of fasting and refraining from nicotine products. Diastolic blood pressure (left brachial artery using an oscillometric method) was measured supine, after 10 minutes rest ("Pre") and repeated after they underwent smoking or vaping changes. The "post challenge" blood pressures were recorded 15-20 minutes post end of exposure. For controls, all measurements were repeated in the same order after a 10 minute break.
Changes in Heart Rate Pre- and Post-challenge.
Time frame: Before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Visit 2 was scheduled up to 4 weeks from enrollment visit, fasting. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge heart rate measured supine, after 10 minutes rest from blood pressure monitor (dinamap). The post challenge heart rates were recorded 15-20 minutes post end of exposure to smoking or vaping challenge completion or in the case of controls after a 10 minute break.
Changes in Brachial Artery Diameter Pre- and Post-challenge
Time frame: before and after smoking/vaping challenge during Visit 2 (up to 4 weeks from enrollment)
Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break.
Changes in Brachial Artery Flow Mediated Dilation (FMD) Pre- and Post-challenge
Time frame: Testing was done after 10 minutes rest and fasting for pre- and post-challenge. The post challenge FMD were recorded 15-20 minuted after end of exposure (up to 4 weeks from enrollment)
Visit 2 was scheduled up to 4 weeks from enrollment visit. Participants attended fasting and refraining from nicotine products for at least 8 hours prior. All visits were in the morning. Pre-challenge ultrasound of brachial artery diameter imaged with ultrasound after resting supine for 10 minutes before and repeated 15-20 minutes after smoking/vaping challenge ended. or in the case of controls after a 10 minute break. The FMD protocol includes measuring % change in resting diameter after 60-90 seconds post fore-arm cuff occlusion release.
Changes in Percent of Sequential Heart Cycles That Differ by More Than 50 ms From Each Other in Length (PNN50, %) Pre- and Post-challenge
Time frame: During V2 (scheduled up to 4 weeks from enrollment) and obtained after 10 minutes of supine rest, before and after smoking/vaping challenge
Expressed as a percentage of beats (supine recordings had be 5 minutes or longer to be valid). We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 1-2 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break.
Changes in Root Mean Square of Successive Differences Between Normal Heart Beats (RMSSD, ms) Pre- and Post-challenge
Time frame: heart rate variability recordings of at least 10 minutes per-challenge and 15 minutes post-challenge (up to 4 weeks from enrollment)
Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability was recorded supine for 10 minutes or more, pre and post smoking/vaping challenge. For controls it was repeated after a 10 minute break.
Changes in Heart Rate Variability Standing Ratio Pre- and Postchallenge
Time frame: Ratio was measured pre- and post- smoking/vaping challenge after completion of the 10 minutes of heart rate variability measures (up to 4 weeks from enrollment)
We used the SphygmoCor system for these recordings (Atcor medical). Participants attended V2 up to 4 weeks after enrollment visit. They came in the morning fasting and refraining from nicotine for at least 8 hours. Heart rate variability standing ratio was assessed pre and post smoking/vaping challenge. For controls is was repeated after a 10-minute break. Ratio between maximal heart rate after abrupt standing from a supine position and the subsequent lowest heart rate value within 40 seconds of peak.
Changes in Predicted Forced Expiatory Volume in 1 Second (FEV1, %) Pre- and Post-challenge
Time frame: before and after smoking/vaping challenge during Visit 2 (1-4 weeks after enrollment visit)
maximum amount of air that the subject can forcibly expel during the first second following maximal inhalation, expressed as a percentage of the predicted normal values in the population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Changes in Forced Vital Capacity (FVC, %) Pre- and Post-Challenge.
Time frame: before and after smoking/vaping challenge during Visit 2 Visit 2 which was scheduled 1 to 4 weeks from enrollment visit, fasting
Amount of air that can be forcibly exhaled after taking the deepest breath possible expressed as a predicted percentage from the normal population. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Changes in Ratio Between Predicted Forced Expiatory Volume in First Second and Predicted Total Vital Capacity (FEV1/FVC Ratio) Pre- and Post-challenge
Time frame: before and after smoking/vaping challenge during Visit 2 (1-4 weeks after enrollment visit)
The post challenge spirometry was recorded <15 minutes post end of exposure. Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Changes in Percent Predicted Forced Expiratory Flow at 25 and 75% of the Pulmonary Volume (FEF 25-75, %) Pre and Pos-challenge
Time frame: Spirometry performed pre-challenge and within 15 minutes post-challenge (up to 4 weeks from enrollment)
Participants attended Visit 2 (1-4 weeks after enrollment visit). They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge spirometry was performed sitting before all other tests and repeated within 15 minutes after smoking/vaping challenge.
Changes in Fractional Exhaled Nitric Oxide (FeNO, Ppb) Pre- and Post-challenge
Time frame: before and after less than 15 minutes from smoking/ vaping product (up to 4 weeks from enrollment)
Participants attended V2 1-4 weeks after enrollment. They came in the morning, fasting and refraining from nicotine exposure for at least 8 hours prior. Pre-challenge FeNO was obtained sitting and repeated within 15 minutes after smoking/vaping challenge.
12 secondary outcomes
Heart Rate (HR)
Time frame: Participants attended V2 generally 1-4 weeks after enrollment with a window that allowed up to 4 weeks after enrollment
Heart Rate Variability (HRV) - Pre Product Use Challenge
Time frame: V2 two was generally scheduled 1-4 weeks after enrollment visit with a window up to 4 weeks. HRV measures obtained after resting supine for 10 minutes
Systolic Blood Pressure (BP)
Time frame: V2 was up to 4 weeks from enrollment visit, after resting supine for 10 minutes
Forced Vital Capacity (FVC)
Time frame: recordings obtained during V2 in the morning, fasting and refraining from nicotine for at least 8 hours. This visit was generally 1-2 weeks after enrollment date with a window up to 4 weeks
Fractional Exhaled Nitric Oxide (FeNO)
Time frame: recordings obtained during V2 in the morning, fasting and refraining from nicotine for at least 8 hours. This visit was generally 1-2 weeks after enrollment date with a window up to 4 weeks
Autonomic Measures - RMSSD
Time frame: v2 was generally 1-2 weeks after enrollment visit, with a window up to 4 weeks from V1
Arterial Pulse Wave Analysis (PWA), Augmentation Index (at 75 Bpm, %)
Time frame: v2 was generally 1-2 weeks after enrollment visit, with a window up to 4 weeks from V1
Exercise Treadmill Stress Test (ETT)-Peak METS
Time frame: Treadmill test done only once at the end of v2 after completion of all other post-challenge assessment tests. V2 was scheduled 1-4 weeks from enrollment vist
Diastolic Blood Pressure (DBP)
Time frame: V2 was generally 1-2 weeks after enrollment with a window up to 4 weeks from V1, recorded after resting supine for 10 minutes
Peak Rate Pressure Product (RPP, Peak Heart Rate Multiplied by Peak Systolic Blood Pressure)
Time frame: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or pretend 10 minute exposure for controls
Heart Rate Reserve (%)
Time frame: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or 10 minute pretend exposure for never-users
60 Seconds Heart Rate Recovery (Beats Per Minute)
Time frame: During V2 (1-4 weeks after enrollment visit) the treadmill stress test was done last, following Nicotine-containing product challenge (users) or pretend 10 minute exposure for controls
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37044158Tattersall MC, Hughey CM, Piasecki TM, Korcarz CE, Hansen KM, Ott NR, Sandbo N, Fiore MC, Baker TB, Stein JH. Cardiovascular and Pulmonary Responses to Acute Use of Electronic Nicotine Delivery Systems and Combustible Cigarettes in Long-Term Users. Chest. 2023 Sep;164(3):757-769. doi: 10.1016/j.chest.2023.03.047. Epub 2023 Apr 10.
- link to full manuscript with published results for this trialLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Our plan includes the creation of a data archive with coded information in computer-readable form for distribution to the scientific community using the procedures outlined below. The information will include a codebook with definitions of variables, variable field locations, summary statistics and any standard scoring. Final data sets will be stripped of identifiers prior to release for sharing (the release of a limited data set containing one or more specific identifiers would be considered if absolutely required by the researcher and if the request meets all University of Wisconsin -Institutional Review Board and Office of Human Research Protections policies. We will make all key variables available via posting of final data codebook and dataset in suitable archives. All shared variables and datasets will be de-identified and approved for sharing by the University of Wisconsin and Institutional Review Board
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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.
James H Stein, MD principal investigator
University of Wisconsin, Madison
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Tobacco Use and E-Cigarette Use, run by University of Wisconsin, Madison 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 21 inclusion and 6 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 21 Aug 2023. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 Aug 2023). 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?
Brachial Artery Flow-Mediated Dilation (FMD)- Pre Challenge (time frame: V2 up to 4 weeks from enrollment visit, fasting). The study lists 16 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 NCT03863509, which also lists 1 linked publication.
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 21 Aug 2023.