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Acute Effects of E-Cigarette Aerosol Inhalation

Primary Purpose

Endothelial Dysfunction, Biochemical Markers

Status
Completed
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Electronic Cigarette Aerosol
Sponsored by
University of Pennsylvania
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Endothelial Dysfunction focused on measuring Inflammation

Eligibility Criteria

18 Years - 35 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

• BMI of 18.5 - 30

Exclusion Criteria:

  • Cancer
  • HIV
  • Mental illness
  • Overt cardio- or neurovascular disease (prior heart attack, stroke, transient ischemic attacks)
  • Serious arrhythmias
  • Bronchospastic disease
  • Upper respiratory tract infection within the past six weeks
  • Chronic medication or antibiotics
  • Claustrophobia / contraindications for MRI

Sites / Locations

  • University of Pennsylvania Perelman School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Healthy, Non-Smokers

Arm Description

Non-nicotinized electronic cigarette aerosol (16 2-second long puffs)

Outcomes

Primary Outcome Measures

Changes in serum protein levels (micrograms) of inflammatory biomarkers (HMGB-1, RAGE, ICAM, CRP) in non-smoking healthy subjects before and after electronic cigarette aerosol inhalation.
High mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE), intercellular adhesion molecule (ICAM1) and C-reactive protein (CRP) will be monitored in serum from subjects by ELISA assays measuring the exact concentration of moieties based on absorbance values emanating from the serum samples. Using standard curves, the amount of these biomarkers will be monitored in the range of nmole or pmole/microgram of serum protein. Measurements will be carried out in triplicate for each sample. Data will be quantified as amount of biomarker/microgram serum protein.
Aortic pulse-wave velocity (meters/second)
Stiffness of aorta
Femoral artery flow-mediated dilation (% fractional change in cross-sectional area)
Degree of dilation of femoral artery during hyperemia (the transient increase in blood flow velocity)
Washout time (seconds)
Transit time of desaturated capillary blood from tissue to the imaging location
Upslope (%HbO2/seconds)
Tissue oxygen resaturation rate
Overshoot (%HbO2)
Degree of overcompensatory effect in supply of oxygen after ischemia
Breath hold index (meters/seconds^2)
Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea

Secondary Outcome Measures

Full Information

First Posted
February 28, 2018
Last Updated
December 2, 2022
Sponsor
University of Pennsylvania
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT03479203
Brief Title
Acute Effects of E-Cigarette Aerosol Inhalation
Official Title
Acute and Long-term Effects of E-Cigarette Aerosol Inhalation on Biomarkers of Endothelial Function and Vascular Reactivity
Study Type
Interventional

2. Study Status

Record Verification Date
December 2022
Overall Recruitment Status
Completed
Study Start Date
May 22, 2018 (Actual)
Primary Completion Date
August 31, 2022 (Actual)
Study Completion Date
August 31, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Pennsylvania
Collaborators
National Institutes of Health (NIH), National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this study is to examine the acute effects of nicotine free electronic cigarette aerosol on vascular function in healthy, non-smokers. This study comprises a portion of a larger study comparing results of vascular function in nonsmokers to vascular function in healthy smokers chronically exposed to nicotinized electronic cigarette aerosol versus conventional cigarettes.
Detailed Description
The purpose of this study is 1) to examine the acute effects of nicotine free e-cigarette aerosol on vascular function in healthy, non-smokers and 2) to examine and compare vascular function in healthy smokers chronically exposed, at baseline and after 12 months, to nicotinized e-cigarette aerosol versus conventional cigarettes as compared to age, gender and body mass index-matched nonsmokers. Vascular function (microvascular reactivity via dynamic femoral oximetry, arterial hyperemia, femoral artery flow-mediated dilation, central pulse-wave velocity, neurovascular reactivity) will be assessed as part of a single integrated MRI protocol. The outcome of the project will provide new insight into the acute and chronic effects of e-cigarette aerosol inhalation in terms of surrogate markers of endothelial dysfunction (EDF), the prime promoter of atherosclerotic cardiovascular disease, and aid toward establishment of future public health advisories.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endothelial Dysfunction, Biochemical Markers
Keywords
Inflammation

7. Study Design

Primary Purpose
Basic Science
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Healthy, Non-Smokers
Arm Type
Experimental
Arm Description
Non-nicotinized electronic cigarette aerosol (16 2-second long puffs)
Intervention Type
Drug
Intervention Name(s)
Electronic Cigarette Aerosol
Intervention Description
16 two-second-long puffs from a non-nicotinized electronic cigarette.
Primary Outcome Measure Information:
Title
Changes in serum protein levels (micrograms) of inflammatory biomarkers (HMGB-1, RAGE, ICAM, CRP) in non-smoking healthy subjects before and after electronic cigarette aerosol inhalation.
Description
High mobility group box-1 (HMGB1), receptor for advanced glycation end products (RAGE), intercellular adhesion molecule (ICAM1) and C-reactive protein (CRP) will be monitored in serum from subjects by ELISA assays measuring the exact concentration of moieties based on absorbance values emanating from the serum samples. Using standard curves, the amount of these biomarkers will be monitored in the range of nmole or pmole/microgram of serum protein. Measurements will be carried out in triplicate for each sample. Data will be quantified as amount of biomarker/microgram serum protein.
Time Frame
Baseline to six hours
Title
Aortic pulse-wave velocity (meters/second)
Description
Stiffness of aorta
Time Frame
Baseline to six Hours
Title
Femoral artery flow-mediated dilation (% fractional change in cross-sectional area)
Description
Degree of dilation of femoral artery during hyperemia (the transient increase in blood flow velocity)
Time Frame
Baseline to six Hours
Title
Washout time (seconds)
Description
Transit time of desaturated capillary blood from tissue to the imaging location
Time Frame
Baseline to six Hours
Title
Upslope (%HbO2/seconds)
Description
Tissue oxygen resaturation rate
Time Frame
Baseline to six Hours
Title
Overshoot (%HbO2)
Description
Degree of overcompensatory effect in supply of oxygen after ischemia
Time Frame
Baseline to six Hours
Title
Breath hold index (meters/seconds^2)
Description
Rate of increase in blood flow velocity in the superior sagittal sinus from intermittent volitional apnea
Time Frame
Baseline to six Hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: • BMI of 18.5 - 30 Exclusion Criteria: Cancer HIV Mental illness Overt cardio- or neurovascular disease (prior heart attack, stroke, transient ischemic attacks) Serious arrhythmias Bronchospastic disease Upper respiratory tract infection within the past six weeks Chronic medication or antibiotics Claustrophobia / contraindications for MRI
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Felix W. Wehrli, Ph.D.
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania Perelman School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33991175
Citation
Zamani P, Proto EA, Wilson N, Fazelinia H, Ding H, Spruce LA, Davila A Jr, Hanff TC, Mazurek JA, Prenner SB, Desjardins B, Margulies KB, Kelly DP, Arany Z, Doulias PT, Elrod JW, Allen ME, McCormack SE, Schur GM, D'Aquilla K, Kumar D, Thakuri D, Prabhakaran K, Langham MC, Poole DC, Seeholzer SH, Reddy R, Ischiropoulos H, Chirinos JA. Multimodality assessment of heart failure with preserved ejection fraction skeletal muscle reveals differences in the machinery of energy fuel metabolism. ESC Heart Fail. 2021 Aug;8(4):2698-2712. doi: 10.1002/ehf2.13329. Epub 2021 May 15.
Results Reference
background
PubMed Identifier
32841482
Citation
Langham MC, Caporale AS, Wehrli FW, Parry S, Schwartz N. Evaluation of Vascular Reactivity of Maternal Vascular Adaptations of Pregnancy With Quantitative MRI: Pilot Study. J Magn Reson Imaging. 2021 Feb;53(2):447-455. doi: 10.1002/jmri.27342. Epub 2020 Aug 25.
Results Reference
background
PubMed Identifier
31990264
Citation
Kligerman S, Raptis C, Larsen B, Henry TS, Caporale A, Tazelaar H, Schiebler ML, Wehrli FW, Klein JS, Kanne J. Radiologic, Pathologic, Clinical, and Physiologic Findings of Electronic Cigarette or Vaping Product Use-associated Lung Injury (EVALI): Evolving Knowledge and Remaining Questions. Radiology. 2020 Mar;294(3):491-505. doi: 10.1148/radiol.2020192585. Epub 2020 Jan 28.
Results Reference
background
PubMed Identifier
33216614
Citation
Chatterjee S, Caporale A, Tao JQ, Guo W, Johncola A, Strasser AA, Leone FT, Langham MC, Wehrli FW. Acute e-cig inhalation impacts vascular health: a study in smoking naive subjects. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H144-H158. doi: 10.1152/ajpheart.00628.2020. Epub 2020 Nov 20.
Results Reference
result
PubMed Identifier
32528311
Citation
Wehrli FW, Caporale A, Langham MC, Chatterjee S. New Insights From MRI and Cell Biology Into the Acute Vascular-Metabolic Implications of Electronic Cigarette Vaping. Front Physiol. 2020 May 21;11:492. doi: 10.3389/fphys.2020.00492. eCollection 2020.
Results Reference
result
PubMed Identifier
31429679
Citation
Caporale A, Langham MC, Guo W, Johncola A, Chatterjee S, Wehrli FW. Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI. Radiology. 2019 Oct;293(1):97-106. doi: 10.1148/radiol.2019190562. Epub 2019 Aug 20.
Results Reference
result
PubMed Identifier
31042077
Citation
Chatterjee S, Tao JQ, Johncola A, Guo W, Caporale A, Langham MC, Wehrli FW. Acute exposure to e-cigarettes causes inflammation and pulmonary endothelial oxidative stress in nonsmoking, healthy young subjects. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 1;317(2):L155-L166. doi: 10.1152/ajplung.00110.2019. Epub 2019 May 1.
Results Reference
result

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Acute Effects of E-Cigarette Aerosol Inhalation

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