Hyperpolarized Xenon-129 MRI for Electronic Cigarette Use Effects on Lungs

(e-cigarette Trial)

Overseen By Yun M Shim, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Virginia

Disqualifiers: Lung disease, CNS disease, coronary artery disease, renal failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

24 Participants Needed

Trial Summary

What is the purpose of this trial?

Over the past 10 years, electronic cigarettes (e-cigarettes, EC) have been commercialized as a "less harmful" alternative to traditional cigarettes.1,2 However, e-cigarettes are believed to cause pulmonary epithelial, endothelial and vascular dysfunction, and to cause murine phenotypes similar to those of human COPD. Recently, "spiked" vape juice has been linked to severe lung damage. Unfortunately, the effects of e-cigarettes on the human lungs are still poorly understood, especially in healthy young adults. Therefore, establishing the health effects of e-cigarettes in humans is of paramount importance to guide medical and regulatory decision making. Its widespread use and immense popularity among teenagers and young adults have caused major concern given potentially significant addictive and detrimental long-term health effects.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Hyperpolarized Xenon-129 MRI for assessing lung function?

Research shows that Hyperpolarized Xenon-129 MRI is effective in assessing lung function by providing detailed images of lung ventilation and gas transfer, which are crucial for understanding lung health. This imaging technique has been promising in managing lung diseases and offers unique insights into lung physiology. ^{1 2 3 4 5}

Is Hyperpolarized Xenon-129 MRI safe for humans?

Research on Hyperpolarized Xenon-129 MRI, used for imaging lungs and other tissues, suggests it is generally safe for humans. Studies have successfully used it in both lung and brain imaging without significant safety concerns reported. ^{2 3 4 6 7}

How does Hyperpolarized Xenon-129 MRI differ from other treatments for assessing lung effects of electronic cigarette use?

Hyperpolarized Xenon-129 MRI is unique because it uses a special form of MRI that can visualize both how well air moves through the lungs and how gases are exchanged in the blood, providing a detailed picture of lung function. Unlike traditional imaging methods, it uses a hyperpolarized gas that enhances the MRI signal, allowing for clearer images of lung ventilation and gas transfer. ^{1 2 4 5 6}

Research Team

Yun M shim, MD

Principal Investigator

University of Virginia

Eligibility Criteria

This trial is for healthy adults aged 21-30 who've used e-cigarettes for over 6 months or non-smokers with less than a 5 pack-year history. Participants must have no lung diseases, recent illnesses, or conditions that MRI can't be performed on (like pregnancy). People with a history of serious health issues like lung disease, infections, anemia, CNS diseases, liver disease, heart disease or renal failure cannot join.

Inclusion Criteria

At baseline health with no recent illnesses or medical conditions that would preclude enrollment as assessed by the Principal Investigator

Ability to understand a written informed consent form and comply with the requirements of the study.

My lung function tests are normal.

Exclusion Criteria

I do not have a history of major brain, heart, liver, or kidney diseases.

You cannot have a history of smoking illegal drugs.

I have not had any infections in the last 6 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Baseline Assessment

Initial assessments including informed consent, demographic data collection, medical history review, and baseline tests such as spirometry and hyperpolarized xenon-129 MRI

4 hours

1 visit (in-person)

Test-Retest Assessment

Assessment of test-retest variability with spirometry, physical exam, and hyperpolarized xenon-129 MRI

3 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after the main assessments

12 months

Treatment Details

Interventions

• Hyperpolarized Xenon-129 MRI

Trial Overview The study uses Hyperpolarized Xenon-129 Magnetic Resonance Imaging (MRI) to investigate the effects of electronic cigarettes on the lungs in young adults. It aims to understand if vaping causes similar damage as seen in certain lung diseases and inform medical guidelines.

Participant Groups

Group I: Visit 2 Duke University Experimental Treatment 1 Intervention

Visit 2 will last about 3 hours, and will occur within 2-12 weeks of Visit 1. The purpose of this study visit is to obtain a measure of basic test-retest variability on 6 e-cigarette users and 6 control subjects. Participants will be selected based on age and sex matching needs at the time of enrollment. During Visit 2, changes in health since Visit 1 will be assessed. In addition, the following will be done in accordance with the parent protocol: 1. The standard MR compatibility screening form will be completed. 2. Spirometry will be performed before and after MR imaging. 3. A limited physical exam 4. Female subjects who could be pregnant will take a urine pregnancy test prior to imaging. 5. Xenon MRI will be performed In addition to the above, the following will be completed: * Carbon monoxide diffusion capacity (DLCO) * Peripheral blood (20mL) and urine

Group II: Visit 1 UVA Experimental Treatment 1 Intervention

Visit 1 will last approximately 4 hours, and will include consenting, collection of data, questionnaires, and procedures as follows: 1. Informed consent 2. Demographic data 3. Smoking history 4. Medical history review 5. Medication review 6. Limited physical exam 7. 6-minute walk test 8. St. George's Respiratory Questionnaire (SGRQ) 9. Baseline dyspnea index (BDI) 10. Chronic respiratory questionnaire (CRQ) 11. PFTs including: 1. Pre-bronchodilator spirometry/ post bronchodilator spirometry. 2. Body plethysmography (static lung volumes) 3. Carbon monoxide diffusion capacity (DLCO) 12. Collection of peripheral blood (20mL), exhaled breath condensate (EBC), and urine 13. Hyperpolarized xenon-129 MRI (HXeMRI) if all eligibility criteria are met

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Duke University

Collaborator

Trials

2,495

Recruited

5,912,000+

Findings from Research

Hyperpolarized (HP) noble gas MRI, particularly using 129Xe, has shown promising results in assessing lung ventilation and regional lung physiology, making it a potential game-changer in pulmonary medicine.

Despite being limited to select academic institutions currently, advancements in polarizer technology suggest that HP 129Xe MRI could soon become more widely available for clinical use, enhancing the diagnostic capabilities for lung conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. Ebner, L., Kammerman, J., Driehuys, B., et al.[2018]

Hyperpolarized 129Xe MRI (HypX-MRI) shows great promise as a new diagnostic tool, enhancing the detectability of lung structures and potentially allowing for better imaging of lipid-rich tissues, which has been challenging with traditional methods.

This technique could help identify issues like ventilation-perfusion mismatch in pulmonary diseases and may also be used for functional MRI studies of the brain, opening new avenues for understanding lung function and brain perfusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. Albert, MS., Balamore, D.[2019]

Hyperpolarized noble gas MRI using helium-3 or xenon-129 enhances MRI signal, making it a promising method for imaging lung function and ventilation.

While there are safety considerations and challenges in clinical application, this technology holds potential for better understanding lung microstructure and function in various pulmonary diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pulmonary hyperpolarized noble gas MRI: recent advances and perspectives in clinical application. Liu, Z., Araki, T., Okajima, Y., et al.[2017]

Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is a new imaging technique that can assess both how well air moves in and out of the lungs (ventilation) and how effectively gases are transferred in the lungs.

While most studies have focused on non-cancer lung diseases, HP 129 Xe MRI shows great potential for improving the management and understanding of lung cancer by evaluating these key lung functions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. Song, EJ., Kelsey, CR., Driehuys, B., et al.[2022]

A new continuous-flow system for producing hyperpolarized xenon (129Xe) has been developed, achieving production rates of 0.3 liters per hour with 64% polarization, significantly improving the availability of this imaging agent for lung MRI studies.

This technology allows for the production of multiliter quantities of hyperpolarized xenon several times daily, enabling more extensive human lung imaging studies that were previously limited by the availability of hyperpolarized gas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. Hersman, FW., Ruset, IC., Ketel, S., et al.[2022]

Hyperpolarized 129Xe MRI is a new imaging technique that allows for detailed lung imaging and can also detect 129Xe in the brain, providing insights into brain parenchyma and blood vessels.

The study outlines specific protocols for using 129Xe MRI in both rodents and humans, highlighting its potential for advanced medical imaging applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. Chahal, S., Prete, BRJ., Wade, A., et al.[2019]

The continuous flow-type hyperpolarizing (CF-HP) system allows for effective lung imaging using hyperpolarized (129)Xe MRI at very low concentrations of xenon, minimizing the anesthetic effects and reducing xenon consumption.

Using a 70% xenon gas mixture resulted in better signal-to-noise ratios for both gas and dissolved-phase images compared to a 3% mixture, although the apparent diffusion coefficient (ADC) was higher with the 3% mixture, indicating a complex relationship between concentration and imaging quality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. Wakayama, T., Kitamoto, M., Ueyama, T., et al.[2015]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

The role of hyperpolarized 129xenon in MR imaging of pulmonary function. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Development of hyperpolarized noble gas MRI. [2019]

3. Ireland pubmed.ncbi.nlm.nih.gov

Pulmonary hyperpolarized noble gas MRI: recent advances and perspectives in clinical application. [2017]

4. Australia pubmed.ncbi.nlm.nih.gov

Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Large production system for hyperpolarized 129Xe for human lung imaging studies. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Hyperpolarized 129 Xe MRI of the mouse lung at a low xenon concentration using a continuous flow-type hyperpolarizing system. [2015]