Developing Hyperpolarized Gas MRI Signatures to Detect and Manage Acute Cellular Rejection

NCT07046910 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 20987-3R01HL173369-01
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Lung transplantation (LT) is the only definitive therapy for many patients with end-stage lung diseases. The supply of donors' lungs is the biggest bottleneck to performing a lung transplant, and many patients die while waiting. Acute Cellular Rejection (ACR) is a significant risk factor for developing chronic allograft failure, a primary reason for death in this patient population. These observations highlight the importance of early diagnosis and management of ACR to prevent chronic graft failure. The preliminary results support the idea that Hyperpolarized Gas Magnetic Resonance Imaging has excellent potential to address this clinical gap. This study hypothesizes that optimized hyperpolarized gas magnetic resonance imaging (HGMRI) signatures can detect early pathophysiologic derangements in lung allografts consistent with ACR. This study also hypothesizes that the optimized HGMRI signatures will correlate with single-cell transcriptomic signatures that reflect dysregulated immune responses associated with ACR.

Conditions

Lung Transplant Rejection

Keywords

lung transplant; hyperpolarized xenon-129 MRI; bronchoscopy

Outcome Measures

Primary Outcomes (4)

• Measurement of Ventilation Defect Percent by MRI (continuous variable %VDP)

  The outcome of Airway abnormalities suggestive of acute rejection

  6 or 12 months then 24 months after the date of lung transplant surgery

• Measurement of Lung gas exchange capacity by MRI (continuous variable of red blood cell gas exchange function called RBC/Gas)

  The outcome of Lung parenchymal gas exchange abnormalities suggestive of acute rejection

  6 or 12 months then 24 months after the date of lung transplant surgery

• Measurement of the Single-cell RNA-sequencing of the bronchoalveolar lavage cells (Top 25 gene signatures over-expressed in lung area with acute rejection)

  What the Single-cell transcriptomic signatures being suggestive of acute rejection

  6 or 12 months then 24 months after the date of last HXe MRI

• Measurement of Pulmonary function test (Spirometry)

  Determining what the Clinical pulmonary function test suggestive of acute rejection

  6 or 12 months then 24 months after the date of last HXe MRI

Study Arms (1)

Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy

EXPERIMENTAL

* blood * urine * Two navigational bronchoscopies and two MRIs for tissue

Diagnostic Test: Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy; Drug: Hyperpolarized Xenon129

Interventions

Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy DIAGNOSTIC_TEST

Hyperpolarized Xenon-129 MRI twice with navigational bronchoscopy twice

Also known as: Lung transplant recipient without HXe MRI prior to navigational bronchoscopy

Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy

Hyperpolarized Xenon129 DRUG

Lung transplant recipient with hyperpolarized Xe129 in MRI as an inhalation contrast agent

Also known as: MRI

Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All subjects must be willing to participate and undergo the procedure, and be managed as outpatients
• All patients who successfully underwent a lung transplant at the University of Virginia
• Followed by the medical lung transplant team for the post-lung transplant rejection surveillance program at the University of Virginia
• a clinical diagnosis of lung transplant within the past 12 months
• absence of any significant allograft dysfunction/rejection at the time of the 12-month surveillance bronchoscopy
• the ability to understand a written informed consent form and comply with the requirements of the study.
• have an acceptable pre-bronchoscopy pulmonary function test: FEV1\>45% before use of any bronchodilator
• Must have acceptable pre-procedural screening studies.
• Complete Blood Count: normal WBC, Hgb, and PLT
• PT: Normal \< 1.2
• Basic Metabolic Panel: Normal
• Scenario 1 (two visits): Standard bronchoscopy with Normal MRI results and without a diagnosis of acute rejection after bronchoscopy.
• Scenario 2 (two visits): Navigational bronchoscopy with abnormal MRI result but without a diagnosis of acute rejection after bronchoscopy by clinical pathology.
• Scenario 3 (three or four visits): Navigational bronchoscopy with abnormal MRI result and a diagnosis of acute rejection after bronchoscopy by clinical pathology at the first visit, the second visit, or both visits.
• Scenario 4 (one visit): Subjects who previously signed Part 2 Substudy corresponding to the First HXe MRI visit of the Part 3 Substudy (6 or 12 month evaluation). They will be asked to join the Part 3 Substudy to undergo a 24-month follow-up evaluation, including MRI and bronchoscopy, as described for Scenarios 1, 2, or 3.

You may not qualify if:

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• Unable to Consent
• Continuous oxygen use at home.
• Blood oxygen saturation of less than 92% as measured by pulse oximetry on the day of imaging.
• FEV1 percent predicted less than 25%.
• Pregnancy or lactation.
• Claustrophobia, inner ear implants, aneurysms or other surgical clips, metal foreign bodies in the eye, pacemakers, or other contraindications to MR scanning. Subjects with any implanted device that cannot be verified as MRI compliant will be excluded.
• Chest circumference greater than that of the xenon MR and/or helium coil. The circumference of the coil is approximately 42 inches.
• History of congenital cardiac disease, chronic renal failure, or cirrhosis.
• Inability to understand simple instructions or to hold still for approximately 10 seconds.
• History of respiratory infection within 2 weeks prior to the MR scan
• History of MI, stroke, and/or poorly controlled hypertension.
• Failure to complete study-related procedures
• Unavailability of a reliable communication network and contacts for follow-up with the second in-house backup contact
• Patient actively smokes.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• University of Virginia: lead

Study Sites (1)

University of Virginia

Charlottesville, Virginia, 22908, United States

RECRUITING

Study Officials

• Yun M Shim, MD

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Carol Bampoe, BS

CONTACT

434.243.9634; cb3ff@uvahealth.org

Roselove Asare, MA

CONTACT

434.243.6074; rnn3b@uvahealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pulmonary and Critical Care Medicine

Model Details: Part 3 Substudy: Testing the diagnostic performance of tissue pathology from blood, urine, and BAL from clinical bronchoscopy with vs. without hyperpolarized Xenon MRI. Determining the HXe MRI responses between before and after ACR treatment. Testing the correlation between HGMRI and scRNA-sequence from areas with vs. without ACR.Testing the correlation between HGMRI and scRNA-sequence and testing the agreement between the diagnoses by HXe MRI vs. tissue pathology from clinical navigational bronchoscopy

Study Record Dates

• First Submitted: June 14, 2025
• First Posted: July 2, 2025
• Study Start: April 1, 2019
• Primary Completion (Estimated): March 30, 2029
• Study Completion (Estimated): March 31, 2029
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: Either at the time of data publication or after the study completion.
• Access Criteria: The access request must meet minimal criteria, such as being a qualified researcher with an approved data-sharing agreement with a research analysis plan. The basic policy is referred to NIH data-sharing policy (funding agency)

Locations

US (1)