Pulmonary Vascular DiseasePhase 2XenonMRINCT03078192
Non-Invasive Diagnosis of Pulmonary Vascular Disease Using Inhaled 129Xe Magnetic Resonance Imaging
A Phase 2 study testing GE-141, Hyperpolarized 129Xenon gas and MRI in people with Pulmonary Vascular Disease, run by Bastiaan Driehuys at 1 site in United States.
Trial summary
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI technqiues for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Vascular Disease
- What is being tested?
- GE-141, Hyperpolarized 129Xenon gas and MRI
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2017to 22 Oct 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Outpatients of either gender, age > 18
- Willing and able to give informed consent and adhere to visit/protocol schedules. (Consent must be given before any study procedures are performed)
- Women of childbearing potential must have a negative urine pregnancy test. This will be confirmed before participation in this investigational protocol.
- Either has a diagnosis of PAH, isolated left heart disease or lung disease (chronic obstructive pulmonary disease or interstitial lung disease) or CTEPH using established clinical criteria.
- Patients undergoing right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease for MRI scans
Who cannot join
- Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
- Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI technqiues for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan. In addition, to characterize perfusion and vascular dimensions directly, patients will undergo a gadolinium-enhanced perfusion scan.
Read the detailed description
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI technqiues for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan. In addition, to characterize perfusion and vascular dimensions directly, patients will undergo a gadolinium-enhanced perfusion scan. The overall aims of the study are as follows:
Aim 1. Perform 129Xe MRI scans in cohorts of patients with PVD, isolated left sided heart failure and isolated lung disease:
1.1 Deploy and optimize 129Xe gas exchange MR spectroscopy and imaging, 129Xe ventilation MRI, structural 1H UTE MRI, and breath-hold 1H perfusion MRI.
1.2 Conduct comprehensive 1H-129Xe MRI in 10 patients with pure pulmonary arterial hypertension (PAH) 1.3 Conduct comprehensive MRI in 10 patients with pure left heart failure 1.4 Conduct comprehensive MRI in 10 patients with pure lung disease but no pulmonary hypertension 1.5 Conduct comprehensive MRI in 5 patients with Chronic thromboembolic pulmonary hypertension (CTEPH) pre and post PTE surgery.
Aim 2. Develop diagnostic criteria for optimizing the sensitivity and specificity of 129Xe MRI for the diagnosis of PVD:
2.1 Develop quantification/scoring methods based on PAH, left heart disease, and lung disease MRI 2.2 Develop reader training materials and train 3 expert readers 2.3 Begin prospective recruitment of 92 patients being evaluated for PAH for MRI scans. These patients may be asked to return for a second scan in the study, at a time no earlier than 48hr after their last xenon dose.
Aim 3. Perform a larger, single-blind study testing the diagnostic accuracy of 129Xe MRI for diagnosis of PVD:
3.1 Trained readers will evaluate 129Xe MRI, while blinded to the subject's disease state and will determine the presence and severity of PVD 3.2 Diagnostic accuracy of 129Xe MRI will be compared to the gold standard of hemodynamic and clinical criteria of PAH
- For this PFTs are not necessary, so they are ancillary
- However, they are a standard way to characterize patients for publications, etc, so we would like to get them if we can. Getting them from the medical record is perfectly adequate for this pur-pose.
- If PFTs are not available from the medical record, they are not so critical as to pre-vent us from enrolling the subject. In publications we will simply acknowledge the realities of COVID for this missing data.
This will be an single-blinded, open-label study enrolling volunteers and patients with pure PAH (10 subjects), pure left heart disease (10 subjects) and pure lung disease (10 subjects) [Aim 1] followed by a larger cohort of 92 subjects being evaluated for PAH [Aim 2]. The investigators plan to consent to 127 subjects.
The sample size calculation is based on testing whether the proposed diagnostic test based on Xe MRI has accuracy comparable to imaging diagnostic procedures in clinical practice, such as mammography. To this end, the investigator proposes to test the hypotheses H0: AUC = 0.72 vs. H1: AUC > 0.85, where area under the curve (AUC) is a summary measure of diagnostic accuracy obtained as the the area under the receiver operating characteristic (ROC) curve which displays the tradeoff between sensitivity and specificity for our proposed Xe MRI based diagnostic test. Here AUC = 0.72 represents a moderately accurate test while AUC = 0.85 represents accuracy comparable to clinical mammography. Based on a one sided, one sample test with variances approximated using the binormal model, the investigator estimates a minimum sample size of 46 normals and 46 with disease will be required to test the above hypotheses at a significance level of 5% with 80% power.
- Conditions
- Pulmonary Vascular Disease
- Being tested
- GE-141, Hyperpolarized 129Xenon gas, MRI
- Keywords
- right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease
- Medical subject headings
- Lung Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GE-141, Hyperpolarized 129Xenon gasDrug
Also called Xe MRI
XeMRI scans will provide 3D images of ventilation and gas exchange. Subjects will inhale HP 129Xe from the dose delivery bags. Then the subject will be moved into the scanner and they will undergo basic 1H localizer and anatomical scans. Once localization is complete, subjects will under-go several MRI scans after inhalation of HPXe
MRIDevice
Perform MRI scans with administration of GE-141, Hyperpolarized 129Xenon
| Study group | Role | What they receive |
|---|---|---|
| Training Set - PVD, Isolated Left Heart Failure, Isolated Lung Disease | Experimental | Patients with Pulmonary Vascular Disease (10 subjects), isolated left sided heart failure (10 subjects), and isolated lung disease(10 subjects) will undergo Xe MRI scans with GE-141, Hyperpolarized 129Xenon gas to develop diagnostic criteria for optimizing the sensitivity and specificity of XeMRI for the diagnosis of PVD Receives: Drug: GE-141, Hyperpolarized 129Xenon gas; Device: MRI |
| Test Set - Pulmonary Vascular Disease | Experimental | 92 subjects being evaluated for undergoing right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease for testing of diagnostic accuracy of XeMRI for diagnosis of PVD Receives: Drug: GE-141, Hyperpolarized 129Xenon gas; Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Participants Determined to be True Positives for Pulmonary Arterial Hypertension
Determine diagnostic accuracy of XeMRI compared to the gold standard of hemodynamic and clinical criteria of pulmonary arterial hypertension (Hemodynamic criteria: mean pulmonary artery pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance ≥ 3 Wood units; Clinical criteria: absence of significant systolic dysfunction (LVEF > 40%) or valvular heart disease (moderate or greater mitral or aortic valve disease); absence of significant obstructive or restrictive lung disease; absence of hypoxemic or hypercarbic respiratory failure; absence of chronic thromboembolic disease; absence of sickle cell anemia or other hemolytic anemias; absence of sarcoidosis).
We used data from Arm 1 (the training set of patients with known pulmonary vascular disease (PVD), isolated left heart disease and lung disease) to determine thresholds for precapillary pulmonary hypertension used for diagnosis in Arm 2 (the test set of pulmonary vascular disease).
Measured: up to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2017
- Study start3 May 2017
- Primary completion22 Oct 2020
- Study completion22 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pulmonary Vascular DiseaseStudies of the same condition, open and under way.
- 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
- Non-randomised
- Intervention model
- Sequential
- Model description
- This will be a single blinded open label study enrolling volunteers and patients with pure PAH (10 subjects), pure left heart disease (10 subjects) and pure lung disease (10 subjects), 5 CTEPH in Aim 1; followed by a larger cohort of 92 subjects with PAH or other cardiac or pulmonary disease for MRI scans
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bastiaan Driehuys
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Sponsor-investigator, Bastiaan Driehuys, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03078192
- Sponsor's protocol ID
- Pro00079617
- Other IDs
- HHSN268201700001C
- Acronym
- XenonMRI
- Status last verified
- Jan 2022
- First submitted
- 24 Feb 2017
- Last updated
- 22 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-Invasive Diagnosis of Pulmonary Vascular Disease Using Inhaled 129Xe Magnetic Resonance Imaging
- ClinicalTrials.gov ID
- NCT03078192
- Acronym / sponsor ID
- XenonMRI / Pro00079617
- Conditions
- Pulmonary Vascular Disease
- Keywords
- right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Bastiaan DriehuysUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 3 May 2017 (actual)
- Primary completion
- 22 Oct 2020 (actual)
- Study completion
- 22 Oct 2020 (actual)
- First posted
- 13 Mar 2017 (actual)
- Results
- Posted 22 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI technqiues for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan. In addition, to characterize perfusion and vascular dimensions directly, patients will undergo a gadolinium-enhanced perfusion scan.
Detailed description
This study seeks to deploy several forms of 129Xe MRI contrast as well as emerging conventional proton MRI technqiues for imaging lung structure and perfusion. Specifically, the 129Xe MRI scans will provide 3D images of ventilation and gas exchange, and spectroscopic indices will be evaluated to test gas exchange dynamics with high temporal resolution. The conventional 1H MRI scans will include a free-breathing ultra-short echo time (UTE) scan that provides images similar to that of a CT scan. In addition, to characterize perfusion and vascular dimensions directly, patients will undergo a gadolinium-enhanced perfusion scan. The overall aims of the study are as follows:
Aim 1. Perform 129Xe MRI scans in cohorts of patients with PVD, isolated left sided heart failure and isolated lung disease:
1.1 Deploy and optimize 129Xe gas exchange MR spectroscopy and imaging, 129Xe ventilation MRI, structural 1H UTE MRI, and breath-hold 1H perfusion MRI.
1.2 Conduct comprehensive 1H-129Xe MRI in 10 patients with pure pulmonary arterial hypertension (PAH) 1.3 Conduct comprehensive MRI in 10 patients with pure left heart failure 1.4 Conduct comprehensive MRI in 10 patients with pure lung disease but no pulmonary hypertension 1.5 Conduct comprehensive MRI in 5 patients with Chronic thromboembolic pulmonary hypertension (CTEPH) pre and post PTE surgery.
Aim 2. Develop diagnostic criteria for optimizing the sensitivity and specificity of 129Xe MRI for the diagnosis of PVD:
2.1 Develop quantification/scoring methods based on PAH, left heart disease, and lung disease MRI 2.2 Develop reader training materials and train 3 expert readers 2.3 Begin prospective recruitment of 92 patients being evaluated for PAH for MRI scans. These patients may be asked to return for a second scan in the study, at a time no earlier than 48hr after their last xenon dose.
Aim 3. Perform a larger, single-blind study testing the diagnostic accuracy of 129Xe MRI for diagnosis of PVD:
3.1 Trained readers will evaluate 129Xe MRI, while blinded to the subject's disease state and will determine the presence and severity of PVD 3.2 Diagnostic accuracy of 129Xe MRI will be compared to the gold standard of hemodynamic and clinical criteria of PAH
- For this PFTs are not necessary, so they are ancillary
- However, they are a standard way to characterize patients for publications, etc, so we would like to get them if we can. Getting them from the medical record is perfectly adequate for this pur-pose.
- If PFTs are not available from the medical record, they are not so critical as to pre-vent us from enrolling the subject. In publications we will simply acknowledge the realities of COVID for this missing data.
This will be an single-blinded, open-label study enrolling volunteers and patients with pure PAH (10 subjects), pure left heart disease (10 subjects) and pure lung disease (10 subjects) [Aim 1] followed by a larger cohort of 92 subjects being evaluated for PAH [Aim 2]. The investigators plan to consent to 127 subjects.
The sample size calculation is based on testing whether the proposed diagnostic test based on Xe MRI has accuracy comparable to imaging diagnostic procedures in clinical practice, such as mammography. To this end, the investigator proposes to test the hypotheses H0: AUC = 0.72 vs. H1: AUC > 0.85, where area under the curve (AUC) is a summary measure of diagnostic accuracy obtained as the the area under the receiver operating characteristic (ROC) curve which displays the tradeoff between sensitivity and specificity for our proposed Xe MRI based diagnostic test. Here AUC = 0.72 represents a moderately accurate test while AUC = 0.85 represents accuracy comparable to clinical mammography. Based on a one sided, one sample test with variances approximated using the binormal model, the investigator estimates a minimum sample size of 46 normals and 46 with disease will be required to test the above hypotheses at a significance level of 5% with 80% power.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- This will be a single blinded open label study enrolling volunteers and patients with pure PAH (10 subjects), pure left heart disease (10 subjects) and pure lung disease (10 subjects), 5 CTEPH in Aim 1; followed by a larger cohort of 92 subjects with PAH or other cardiac or pulmonary disease for MRI scans
| Arm | Type | Receives |
|---|---|---|
| Training Set - PVD, Isolated Left Heart Failure, Isolated Lung Disease | Experimental | Drug: GE-141, Hyperpolarized 129Xenon gas, Device: MRIPatients with Pulmonary Vascular Disease (10 subjects), isolated left sided heart failure (10 subjects), and isolated lung disease(10 subjects) will undergo Xe MRI scans with GE-141, Hyperpolarized 129Xenon gas to develop diagnostic criteria for optimizing the sensitivity and specificity of XeMRI for the diagnosis of PVD |
| Test Set - Pulmonary Vascular Disease | Experimental | Drug: GE-141, Hyperpolarized 129Xenon gas, Device: MRI92 subjects being evaluated for undergoing right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease for testing of diagnostic accuracy of XeMRI for diagnosis of PVD |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Outpatients of either gender, age > 18
- Willing and able to give informed consent and adhere to visit/protocol schedules. (Consent must be given before any study procedures are performed)
- Women of childbearing potential must have a negative urine pregnancy test. This will be confirmed before participation in this investigational protocol.
- Either has a diagnosis of PAH, isolated left heart disease or lung disease (chronic obstructive pulmonary disease or interstitial lung disease) or CTEPH using established clinical criteria.
- Patients undergoing right heart catheterization for evaluation of PAH or other cardiac or pulmonary disease for MRI scans
Key exclusion criteria (2 listed)
- Medical or psychological conditions which, in the opinion of the investigator, might create undue risk to the subject or interfere with the subject's ability to comply with the protocol requirements
- Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
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 |
|---|---|---|
| GE-141, Hyperpolarized 129Xenon gasAlso: Xe MRIXeMRI scans will provide 3D images of ventilation and gas exchange. Subjects will inhale HP 129Xe from the dose delivery bags. Then the subject will be moved into the scanner and they will undergo basic 1H localizer and anatomical scans. Once localization is complete, subjects will under-go several MRI scans after inhalation of HPXe | Drug | Test Set - Pulmonary Vascular Disease, Training Set - PVD, Isolated Left Heart Failure, Isolated Lung Disease |
| MRIPerform MRI scans with administration of GE-141, Hyperpolarized 129Xenon | Device | Test Set - Pulmonary Vascular Disease, Training Set - PVD, Isolated Left Heart Failure, Isolated Lung Disease |
Primary outcome
Participants Determined to be True Positives for Pulmonary Arterial Hypertension
Time frame: up to 2 weeks
Determine diagnostic accuracy of XeMRI compared to the gold standard of hemodynamic and clinical criteria of pulmonary arterial hypertension (Hemodynamic criteria: mean pulmonary artery pressure > 20 mmHg, pulmonary arterial wedge pressure ≤ 15 mmHg, and pulmonary vascular resistance ≥ 3 Wood units; Clinical criteria: absence of significant systolic dysfunction (LVEF > 40%) or valvular heart disease (moderate or greater mitral or aortic valve disease); absence of significant obstructive or restrictive lung disease; absence of hypoxemic or hypercarbic respiratory failure; absence of chronic thromboembolic disease; absence of sickle cell anemia or other hemolytic anemias; absence of sarcoidosis). We used data from Arm 1 (the training set of patients with known pulmonary vascular disease (PVD), isolated left heart disease and lung disease) to determine thresholds for precapillary pulmonary hypertension used for diagnosis in Arm 2 (the test set of pulmonary vascular disease).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
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 GE-141, Hyperpolarized 129Xenon gas and MRI in people with Pulmonary Vascular Disease, run by Bastiaan Driehuys 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 5 inclusion and 2 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: finished, as of the sponsor's last update on 22 Feb 2022. 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?
Yes. Results are posted in the registry (first posted 22 Feb 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Participants Determined to be True Positives for Pulmonary Arterial Hypertension (time frame: up to 2 weeks). 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 22 Feb 2022; AzTrials last refreshed its copy on 8 Nov 2026.