A Phase 2 interventional study of Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy and Hyperpolarized Xenon129 in Lung Transplant Rejection, sponsored by University of Virginia. Recruiting at 1 site in United States. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-03-17.
Sponsored by University of Virginia · Phase 2, Interventional, and Diagnostic
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.
Lung transplantation (LT) is the only definitive therapy for subjects 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. Many lung transplant recipients experience at least one acute rejection episode after transplantation. 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 (HGMRI) signatures have excellent potential to address this clinical gap. In lung transplant patients without suspicion of ACR, HGMRI detected subtle, regional abnormalities in pulmonary physiology that were not detected by pulmonary function tests (PFTs) or high-resolution chest computer tomography (HRCT). Biopsy-proven regions of ACR in these subjects exhibited worse airflow and gas exchange HGMRI signatures, which corroborated well with the tissue pathology diagnosis of ACR. This data demonstrates the potential of HGMRI signatures to detect ACR even when existing clinical tools cannot. By merging anatomic CT and physiologic HGMRI readouts, the previous study developed a method to identify the airways that led to the allograft segments with abnormal HGMRI signatures. Then, a method to sample these areas of allografts is enabled during routine surveillance bronchoscopy by mapping the airways leading to dysfunctional allograft regions to enhance the diagnostic accuracy of clinical bronchoscopy. The primary molecular driver of ACR is the exaggerated host immune response to the donor's lungs. The anticipated results are that within the same subject, the single-cell transcriptome of cells from lung regions with abnormal HGMRI signatures would be more immunologically abnormal than those with normal HGMRI signatures. The hypothesis is that optimized HGMRI signatures can detect early pathophysiologic derangements in lung allografts consistent with ACR. The second hypothesis is that the optimized HGMRI signatures correlate with single-cell transcriptomic signatures reflecting the dysregulated immune responses underlying ACR. This study proposes: Aim 1: Determine the optimized HGMRI signatures to detect early regional allograft dysfunction consistent with ACR in lung allografts at the baseline Visit 1 (V1); Aim 2: Determine how the within-subject longitudinal changes in regional HGMRI signatures over a 1-year follow-up Visit 2 (V2) correlate with a clinical diagnosis of ACR.
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Of its 60 completed or terminated interventional studies of FDA-regulated products, 41 (68%) have results posted.
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Basic Metabolic Panel: Normal
Exclusion Criteria:
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Claustrophobic or too large to fit into the available MR chest RF coils.
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* 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
Hyperpolarized Xenon-129 MRI twice with navigational bronchoscopy twice
Also known as: Lung transplant recipient without HXe MRI prior to navigational bronchoscopy
Lung transplant recipient with hyperpolarized Xe129 in MRI as an inhalation contrast agent
Also known as: MRI
Measurement of Ventilation Defect Percent by MRI (continuous variable %VDP)
The outcome of Airway abnormalities suggestive of acute rejection
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 6 or 12 months then 24 months after the date of last HXe MRI
Plan to share: Yes — Deidentified individual-level data will be made available at publication or at the time of study completion per the funding agency's policy (NIH/NHLBI).
Supporting information: Csr
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