Lung Transplant RejectionPhase 2NCT07046910
Developing Hyperpolarized Gas MRI Signatures to Detect and Manage Acute Cellular Rejection
A Phase 2 study testing Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy and Hyperpolarized Xenon129 in people with Lung Transplant Rejection, run by University of Virginia at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Lung Transplant Rejection
- What is being tested?
- Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy and Hyperpolarized Xenon129
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2019to 31 Mar 2029
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- All subjects must be willing to participate and undergo the procedure, and be managed as outpatients
- HXe MRI-specific Inclusion
- 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
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- 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.
Who cannot join
- <!-- -->
- 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.
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- 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.
- Before 48 hours, any event being considered to be too risky to preclude surveillance bronchoscopy: SaO2 <90%, >16 puffs/24 hours of short-acting β-agonist (SABA), worsening symptoms prompting the use of any inhalers, FEV1 < 45% before using a bronchodilator.
- acute or chronic renal failure
- uncontrolled coronary artery disease or congestive heart failure; uncontrolled diabetes mellitus; uncontrolled hypertension, liver disease; history of neurologic diseases, including stroke, any disease concerning fibrotic processes.
- Pregnant females will be excluded
- Claustrophobic or too large to fit into the available MR chest RF coils.
- -
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Virginia
Charlottesville, Virginia, 22908
Roselove Asare, MA, 434-243-6074, rnn3b@uvahealth.org
Carol Bampoe, BA, 434.243.9634, cb3ff@uvahealth.org
About this study
Official title: Advanced Immunoclinical Phenotyping of Rejection in Lung Transplant
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.
Read the detailed description
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.
- Conditions
- Lung Transplant Rejection
- Being tested
- Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy, Hyperpolarized Xenon129
- Keywords
- lung transplant, hyperpolarized xenon-129 MRI, bronchoscopy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sub study (Active): Two Lung MRI study with two navigational BronchoscopyDiagnostic test
Also called Lung transplant recipient without HXe MRI prior to navigational bronchoscopy
Hyperpolarized Xenon-129 MRI twice with navigational bronchoscopy twice
Hyperpolarized Xenon129Drug
Also called MRI
Lung transplant recipient with hyperpolarized Xe129 in MRI as an inhalation contrast agent
| Study group | Role | What they receive |
|---|---|---|
| Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy | Experimental | * blood
* urine
* Two navigational bronchoscopies and two MRIs for tissue Receives: Diagnostic Test: Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy; Drug: Hyperpolarized Xenon129 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measurement of Ventilation Defect Percent by MRI (continuous variable %VDP)
The outcome of Airway abnormalities suggestive of acute rejection
Measured: 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
Measured: 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
Measured: 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
Measured: 6 or 12 months then 24 months after the date of last HXe MRI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Jul 2025
- Study start1 Apr 2019
- Primary completion30 Mar 2029 (estimated)
- Study completion31 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung Transplant RejectionStudies of the same condition, open and under way.
- More trials run by University of VirginiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Virginia
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Y. Michael Shim, MD, University of Virginia
- Investigators
- Yun M Shim, MD, Principal investigator, University of Virginia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07046910
- Sponsor's protocol ID
- 20987-3
- Other IDs
- R01HL173369-01
- Status last verified
- Mar 2026
- First submitted
- 14 Jun 2025
- Last updated
- 17 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- 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).
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Advanced Immunoclinical Phenotyping of Rejection in Lung Transplant
- ClinicalTrials.gov ID
- NCT07046910
- Acronym / sponsor ID
- 20987-3
- Conditions
- Lung Transplant Rejection
- Keywords
- lung transplant, hyperpolarized xenon-129 MRI, bronchoscopy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of VirginiaUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- 30 Mar 2029 (estimated)
- Study completion
- 31 Mar 2029 (estimated)
- First posted
- 2 Jul 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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
| Arm | Type | Receives |
|---|---|---|
| Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy | Experimental | Diagnostic Test: Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy, Drug: Hyperpolarized Xenon129* blood * urine * Two navigational bronchoscopies and two MRIs for tissue |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- All subjects must be willing to participate and undergo the procedure, and be managed as outpatients
- HXe MRI-specific Inclusion
- 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
Key exclusion criteria (21 listed)
- <!-- -->
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sub study (Active): Two Lung MRI study with two navigational BronchoscopyAlso: Lung transplant recipient without HXe MRI prior to navigational bronchoscopyHyperpolarized Xenon-129 MRI twice with navigational bronchoscopy twice | Diagnostic test | Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy |
| Hyperpolarized Xenon129Also: MRILung transplant recipient with hyperpolarized Xe129 in MRI as an inhalation contrast agent | Drug | Substudy(Active): Two Longitudinal Lung MRI study with two navigational Bronchoscopy |
Primary outcome
Measurement of Ventilation Defect Percent by MRI (continuous variable %VDP)
Time frame: 6 or 12 months then 24 months after the date of lung transplant surgery
The outcome of Airway abnormalities suggestive of acute rejection
Measurement of Lung gas exchange capacity by MRI (continuous variable of red blood cell gas exchange function called RBC/Gas)
Time frame: 6 or 12 months then 24 months after the date of lung transplant surgery
The outcome of Lung parenchymal gas exchange abnormalities suggestive of acute rejection
Measurement of the Single-cell RNA-sequencing of the bronchoalveolar lavage cells (Top 25 gene signatures over-expressed in lung area with acute rejection)
Time frame: 6 or 12 months then 24 months after the date of last HXe MRI
What the Single-cell transcriptomic signatures being suggestive of acute rejection
Measurement of Pulmonary function test (Spirometry)
Time frame: 6 or 12 months then 24 months after the date of last HXe MRI
Determining what the Clinical pulmonary function test suggestive of acute rejection
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2026.
- Individual participant dataSharing planned: 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).
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A Study to Test How Effective Belumosudil Tablets Are for Treating Adult Participants With Chronic Lung Allograft Dysfunction
Lung Transplant Rejection
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A Phase 1 Clinical Trial of Siltuximab for the Treatment of Antibody-Mediated Rejection After Lung Transplantation
Antibody Mediated Rejection of Lung Transplant
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Belumosudil to Block Chronic Lung Allograft Dysfunction (CLAD) in High Risk Lung Transplant Recipients
Lung Transplant
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Prospective Multicenter Research on Donor and Recipient Management Strategies to Improve Lung Transplant Outcomes
Lung Transplant; Complications, Lung Transplant; Infection or Inflammation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yun M Shim, MD principal investigator
University of Virginia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sub study (Active): Two Lung MRI study with two navigational Bronchoscopy and Hyperpolarized Xenon129 in people with Lung Transplant Rejection, run by University of Virginia at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Carol Bampoe, BS (434.243.9634, cb3ff@uvahealth.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Measurement of Ventilation Defect Percent by MRI (continuous variable %VDP) (time frame: 6 or 12 months then 24 months after the date of lung transplant surgery). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Mar 2026.