E-Cigarette Effects on Markers of Cardiovascular and Pulmonary Disease

NCT03863509 | Completed Results DMC

• 5 other identifiers: 2017-10901R01HL139331-01Protocol Version 4/26/2021A534225SMPH\MEDICINE\CARDIOLOGY
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Tobacco Use; E-Cigarette Use; Cardiovascular Diseases; Pulmonary Disease

Keywords

vape; E-Cigarette; E-cig

Outcome Measures

Primary Outcomes (16)

• 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.

  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

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  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.

  before and after less than 15 minutes from smoking/ vaping product (up to 4 weeks from enrollment)

Secondary Outcomes (12)

• Heart Rate (HR)

  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

  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)

  V2 was up to 4 weeks from enrollment visit, after resting supine for 10 minutes

• Forced Vital Capacity (FVC)

  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)

  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

Study Arms (3)

Exclusive Smokers

Smokes Daily; \>/= 5 cigarettes/day for last 6 months

Behavioral: Cigarettes

Exclusive E-Cig users

E-cig usage \>/= 5 days/week for last 3 months

Behavioral: E-Cigarettes

Never users

\< 100 cigarettes in lifetime, none for \> 5 years; \< 3 E-cig usage in lifetime

Interventions

Cigarettes BEHAVIORAL

smokes daily

Exclusive Smokers

E-Cigarettes BEHAVIORAL

E-cigarette usage \>/= 5 days/week

Also known as: E-cig, Vape

Exclusive E-Cig users

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

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).

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Related Publications (1)

• 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.

  PMID: 37044158 RESULT

Related Links

• link to full manuscript with published results for this trial

MeSH Terms

Conditions

Tobacco Use; Vaping; Cardiovascular Diseases; Lung Diseases

Interventions

Tobacco Products; Electronic Nicotine Delivery Systems

Condition Hierarchy (Ancestors)

Behavior; Smoking; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Smoking Devices; Manufactured Materials; Technology, Industry, and Agriculture

Limitations and Caveats

Observational study, changes observed with product challenge are not proof of the causal effects.

Results Point of Contact

• Title: Dr James H. Stein
• Organization: University of Wisconsin-Madison

jhs@medicine.wisc.edu

608-262-2075

Study Officials

• James H Stein, MD

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2019
• First Posted: March 5, 2019
• Study Start: March 5, 2019
• Primary Completion: March 9, 2022
• Study Completion: March 9, 2022
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: After data has been collected and analyzed.
• Access Criteria: In accord with an Institutional Review Board-approved study consent that will permit sharing of study data sets under University of Wisconsin and Institutional Review Board policies, University of Wisconsin Center for Tobacco Research and Intervention will act under its own auspices as the hub for making data related to these topics available. We will make the final de-identified study dataset available by request from other researchers in accord with NHLBI policy.

Locations

US (1)