Dissolved Phase HXe-129 MRI: A Novel Biomarker to Quantify Pulmonary Pathology (ECig)

Dissolved Phase Hyperpolarized Xenon-129 MRI: a Novel Biomarker to Quantify Pulmonary Pathology in Healthy Participants and E-cigarette Users

A two-center, longitudinal assessment of 40 electronic cigarette users and 40 healthy controls at the initial visit and a follow-up visit 12 months later. This study will determine the impact of electronic cigarette use on pulmonary gas exchange capacity and then corroborate the Hyperpolarized Xenon MRI (HXeMRI) results with the cardiopulmonary stress test at the initial visit and a follow-up visit 12 months later.

Study Overview

• Status: Recruiting
• Conditions: Electronic Cigarette Related Lung Damage
• Intervention / Treatment: Diagnostic test: Cardiopulmonary Stress Test; Diagnostic test: Pulmonary Function Test; Diagnostic test: Chest CT; Drug: Hyperpolarized xenon 129

Detailed Description

Electronic cigarettes have been commercialized as a "less harmful" alternative to traditional cigarettes. Electronic cigarettes generate vapor from ingredients containing well-known toxic materials such as carbonyls, tobacco-specific N-nitrosamines, and heavy metals. Nonhuman studies show that Electronic cigarettes cause pulmonary epithelial, endothelial, and vascular dysfunction. Electronic cigarette use has also been associated with cardiac and pulmonary diseases, including severe respiratory failure. Our preliminary studies suggest that we can detect subtle early changes in healthy young e-cigarette users by hyperpolarized xenon-129 MR imaging. We anticipate the following results from the three primary analyses. First, there will be significantly impaired gas exchange in electronic cigarette users compared to healthy controls at the initial and follow-up visits. Second, gas exchange impairment in electronic cigarette users will increase after an additional 12 months of electronic cigarette use. Further, as a secondary analysis, we speculate that because electronic cigarette users exhaust their cardiopulmonary reserve at rest, they will have reduced physical fitness detectable by the 6-minute walk and Cardio-pulmonary exercise tests.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Roselove Asare, MA; Phone Number: 4342436074; Email: rnn3b@virginia.edu
• Study Contact Backup: Name: Caleigh Smith, BS; Phone Number: 434-243-1140; Email: RJT3QF@uvahealth.org

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University
      • Principal Investigator: Joseph Mammarappallil, MD
      • Contact: Cody Blanton, BS; Phone Number: 919-668-7575; Email: cody.blanton@duke.edu
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
      • Principal Investigator: Yun M Shim, MD
      • Contact: Yun M Shim, MD; Phone Number: 434-924-5210; Email: yss6n@virginia.edu
      • Contact: Roselove N Asare, MA; Phone Number: 434-243-6074; Email: rnn3b@virginia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Ages between 18 and 35 years old.
2. At their baseline health
3. Ability to understand a written informed consent form and comply with the requirements of the study.
4. Exclusive long-term, recent, and greater than six months continuous e-cigarette use with greater than three days a week frequency.
5. Users of "closed-container" and "pre-packaged" electronic cigarette juices that must contain nicotine.

6. Healthy subjects must be at baseline normal spirometry with or without bronchodilator, plethysmograph lung volume, DLCO, and 6-minute walk by ATS/ERS with Global Lung Initiative Reference. (PFT will be completed during a screening visit); Ecigarette users can have normal spirometry (FEV1/FVC>70) or abnormal spirometry (FEV1/FVC 26-70)

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Exclusion Criteria:

1. History of any other lung disease
2. History of brain diseases including stroke (CNS) and dementia, end-stage liver disease, coronary artery disease, renal failure
3. Acute infection of any kind previous 6 weeks
4. Pregnancy or a possibility of pregnancy
5. Anemia
6. Inability to undergo PFT, CPET, or MR imaging (usual clinical standard criteria for MRI)
7. Prior cigarette smoking of greater than one pack-year within six months before enrolling in the study.
8. Using a non-closed container, custom-made electronic cigarette juice, or inability for the study team to access "closed-container" and "pre-packaged" electronic cigarette juice for chemical analysis

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Healthy Participants; Young, healthy subjects without any lung disease or other inflammatory diseases.	Diagnostic test: Cardiopulmonary Stress Test; Exercise stress test to evaluate cardiac and pulmonary fitness.; Other Names: CPET; Diagnostic test: Pulmonary Function Test; Standard clinic pulmonary function test to evaluate lung function; Other Names: PFT; Diagnostic test: Chest CT; Clinical standard chest computer tomography to evaluate any lung tissue scars or air movement.; Drug: Hyperpolarized xenon 129; Determine the impact of e-cigarette use on pulmonary gas exchange capacity in interstitial tissues and capillaries using hyperpolarized xenon-129 MRI.; Other Names: 129HxeMRI
Experimental: eCig user; Young, otherwise healthy subjects who have used electronic cigarettes for at least 6 months past year.	Diagnostic test: Cardiopulmonary Stress Test; Exercise stress test to evaluate cardiac and pulmonary fitness.; Other Names: CPET; Diagnostic test: Pulmonary Function Test; Standard clinic pulmonary function test to evaluate lung function; Other Names: PFT; Diagnostic test: Chest CT; Clinical standard chest computer tomography to evaluate any lung tissue scars or air movement.; Drug: Hyperpolarized xenon 129; Determine the impact of e-cigarette use on pulmonary gas exchange capacity in interstitial tissues and capillaries using hyperpolarized xenon-129 MRI.; Other Names: 129HxeMRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute effects of e-cig in e-cig users before and after using one usual dose at baseline and 12 months follow-up	Cardiopulmonary stress test maximum oxygen uptake	baseline and 12 months follow-up
Acute effects of e-cig in e-cig users before and after using one usual dose at baseline and 12 months follow-up	Pulmonary Function Test with 6 minute walk test	Baseline and 12 months follow up
Comparison between e-cig user vs. healthy participants at baseline and 12 month later	Hyperpolarized MRI (ventilation defect, RBC/Gas, Membrane/Gas, and RBC/membrane numbers) capillaries using HXeMRI, and corroborate the HXeMRI signatures with the CPET for 40 healthy participants and 40 e-cigarette users use at an initial visit (V1) and a follow-up visit 12-months later (V2).	baseline and 12 month follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Effects of eCig use at baseline and 12 months follow-up	blood levels of 32 chemical toxins	baseline and 12 months follow-up

Collaborators and Investigators

• Sponsor: Y. Michael Shim, MD
• Collaborators: Duke University; George Mason University
• Investigators: Principal Investigator: Yun M Shim, MD, University of Virginia

Study record dates

Study Major Dates

• Study Start (Actual): December 19, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: November 15, 2024
• First Submitted That Met QC Criteria: February 25, 2025
• First Posted (Actual): March 4, 2025

Study Record Updates

• Last Update Posted (Actual): March 17, 2026
• Last Update Submitted That Met QC Criteria: March 14, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: vaping; lung damage; hyperpolarized xenon-129 MRI; cardiopulmonary stress test; healthy young adult
• Additional Relevant MeSH Terms: Behavior; Smoking; Vaping; Investigative Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Respiratory System; Diagnostic Techniques, Cardiovascular; Heart Function Tests; Ergometry; Respiratory Function Tests; Exercise Test
• Other Study ID Numbers: 230348; Pro00116167 (Other Identifier: Duke University IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: As a part of publications.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No