Hyperpolarized Xenon-129 MR Imaging of the Lung (e-cigarette)

• ClinicalTrials.gov Identifier: NCT04662658
• Recruitment Status: Recruiting
• First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Sponsor: University of Virginia
• Collaborator: Duke University
• Information provided by (Responsible Party): Y. Michael Shim, MD, University of Virginia

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
E-Cig Use	Drug: Hyperpolarized Xenon -129 MRI	Phase 1; Phase 2

Detailed Description:

This exploratory proposal will exploit 3D hyperpolarized xenon-129 MRI (HXeMRI), an imaging tool that our research group has pioneered, to address this urgent need. The HXeMRI technique has unique abilities to quantify regional ventilation (airflow), and gas uptake by tissue (interstitium), and blood (pulmonary vasculature) in the human lung with high spatial resolution. HXeMRI is anticipated to overcome the limitations of PFT and MDCT. Because HXeMRI images are acquired in a single breath-hold, pixel-based ratio maps can quantify xenon movement crossing from airways to tissue and finally to RBCs. The calculated ratios are closely related to important lung physiological factors: Tissue-to-Gas ratio (T/G) reflects tissue integrity and alveolar surface-to-volume ratio; RBC-to-Gas ratio (R/G) reflects overall gas exchange efficiency from the airspaces to the blood, and RBC-to-Tissue ratio (R/T) reflects capillary perfusion and gas-blood barrier functional integrity. The sensitivity and specificity of these parameters have been shown to be highly relevant in clinical arenas. For example, decreases in gas uptake by tissue and blood are consistently found in COPD and interstitial lung disease. Alteration of gas exchange measured by RBC-to-tissue ratio in COPD and asthma is associated with changes in the alveolar septal wall and capillary perfusion. Investigators have found regionally heterogeneous tissue gas uptake and impairment of gas exchange in idiopathic pulmonary fibrosis. This actively-funded NIH study has found highly heterogeneous airway obstruction and alterations of gas exchange in patients with cystic fibrosis that are routinely undetectable by clinical PFT. These results demonstrate the unique advantages of HXeMRI to quantitatively assess comprehensive regional physiology of microscopic pulmonary compartments.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to one of two groups in parallel for the duration of the study
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Hyperpolarized Xenon-129 MR Imaging of the Lung:E-cigarette Sub-study
• Actual Study Start Date: November 5, 2020
• Estimated Primary Completion Date: December 2022
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Visit 1 UVA; Visit 1 will last approximately 4 hours, and will include consenting, collection of data, questionnaires, and procedures as follows: Informed consent; Demographic data; Smoking history; Medical history review; Medication review; Limited physical exam; 6-minute walk test; St. George's Respiratory Questionnaire (SGRQ); Baseline dyspnea index (BDI); Chronic respiratory questionnaire (CRQ); PFTs including: Pre-bronchodilator spirometry/ post bronchodilator spirometry. Body plethysmography (static lung volumes) Carbon monoxide diffusion capacity (DLCO); Collection of peripheral blood (20mL), exhaled breath condensate (EBC), and urine; Hyperpolarized xenon-129 MRI (HXeMRI) if all eligibility criteria are met	Drug: Hyperpolarized Xenon -129 MRI; e-cigarette sub-study; Other Name: MRI with xenon-129 gas
Visit 2 Duke University; 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: The standard MR compatibility screening form will be completed.; Spirometry will be performed before and after MR imaging.; A limited physical exam; Female subjects who could be pregnant will take a urine pregnancy test prior to imaging.; 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	Drug: Hyperpolarized Xenon -129 MRI; e-cigarette sub-study; Other Name: MRI with xenon-129 gas

Outcome Measures

Primary Outcome Measures :

1. Hyperpolarized xenon-129 MRI of the lung: e-cig sub-study [ Time Frame: 12 months ]
   To measure the pulmonary physiologic effects of e-cigarette use in young adults with less than a 5 pack-year history of smoking traditional cigarettes.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

1. Male and female subjects 21-30 years of age
2. At baseline health with no recent illnesses or medical conditions that would preclude enrollment as assessed by the Principal Investigator
3. Ability to understand a written informed consent form and comply with the requirements of the study.
4. E-cigarette use for more than 6 months preceding the date of enrollment and less than a 5 pack year smoking history (e-cigarette users) OR less than a 5 pack year smoking history (non-smoker group).
5. No diagnosis of any lung disease (pre-bronchodilator FEV1/FVC normal on the day of screening defined by > 95thCI of NHANES III, ATS/ERS guideline)

Exclusion Criteria:

1. History of any lung disease
2. Control (non-smoking) group: History of illegal drug use by inhalation
3. History of CNS disease including stroke and dementia, end-stage liver disease, coronary artery disease, renal failure
4. Acute infection of any kind in the previous 6 weeks
5. Pregnancy or a possibility of pregnancy
6. Anemia
7. Inability to undergo MR imaging based on the standard clinical criteria for MRI

Contacts and Locations

Contacts

Contact: Roselove Asare; 434-243-6074; rnn3b@virginia.edu

Locations

United States, Virginia

Snyder Building 480 Ray C. Hunt Drive; Recruiting

Charlottesville, Virginia, United States, 22908

Contact: Roselove Asare, MA 434-243-6074 rnn3b@virginia.edu

Principal Investigator: Yun M Shim, MD

Sponsors and Collaborators

University of Virginia

Duke University

Investigators

• Principal Investigator: Yun M shim, MD; University of Virginia

More Information

• Responsible Party: Y. Michael Shim, MD, Medical Doctor, University of Virginia
• ClinicalTrials.gov Identifier: NCT04662658
• Other Study ID Numbers: 13740
• First Posted: December 10, 2020
• Last Update Posted: December 10, 2020
• Last Verified: December 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Y. Michael Shim, MD, University of Virginia:

e-cigarette use with young adults

Additional relevant MeSH terms:

Xenon; Anesthetics, Inhalation; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Physiological Effects of Drugs