Xenon MRI for Pulmonary Arterial Hypertension
(Jupiter PH Trial)
Recruiting in Palo Alto (17 mi)
Overseen bySudarshan Rajagopal, MD, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Bastiaan Driehuys
Disqualifiers: Heart disease, Cancer, Sickle cell, others
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?
This trial uses a special MRI scan with a gas to monitor lung function in patients with severe lung disease. It targets those being monitored over time to better understand and track their condition. The MRI technique provides detailed lung function measurements and is well-tolerated, allowing for thorough exploration of lung function.
Will I have to stop taking my current medications?
The trial protocol does not specify whether you need to stop taking your current medications. However, if you are in Cohort 2, you must be either treatment naïve or have started treatment within the last 3 months.
What data supports the effectiveness of the treatment 129Xe Hyperpolarized, Hyperpolarized 129Xe, 129Xe MRI/MRS for Pulmonary Arterial Hypertension?
How is the treatment 129Xe Hyperpolarized MRI different from other treatments for pulmonary arterial hypertension?
129Xe Hyperpolarized MRI is unique because it is a non-invasive imaging technique that allows doctors to see how well the lungs are working by assessing both ventilation (airflow) and gas exchange. Unlike traditional treatments that focus on managing symptoms, this method provides detailed images of lung function, which can help in diagnosing and monitoring the progression of pulmonary arterial hypertension.34567
Eligibility Criteria
This trial is for adults aged 18-75 with Pulmonary Hypertension (PH), specifically those who are newly diagnosed or have started treatment within the last three months. Participants must be able to consent and follow the study schedule, and women of childbearing age need a negative pregnancy test before MRI scans. Those awaiting lung transplants can join too, but not if they have severe liver disease, heart issues, active cancer, sickle cell anemia or conditions preventing MRI use.Inclusion Criteria
Willing and giving informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed)
Willing and able to give informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed)
I am between 18 and 75 years old.
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Exclusion Criteria
Prisoners and pregnant women will not be approached for the study
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
I have sickle cell anemia.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo 129Xe MRI scans and standard-of-care assessments including labs, echocardiography, and six-minute walk distance
24 months
Follow-up
Participants are monitored for safety and effectiveness after treatment, with 6-month follow-up appointments
5 years
Treatment Details
Interventions
- 129Xe Hyperpolarized (Gas)
Trial OverviewThe trial is testing how a type of imaging called Xenon 129 Magnetic Resonance Imaging (MRI) can show changes in lung function and blood flow in patients with different types of Pulmonary Hypertension. It aims to understand how these images change with disease progression or after starting treatment.
Participant Groups
2Treatment groups
Experimental Treatment
Group I: following pulmonary arterial hypertension subjectsExperimental Treatment1 Intervention
Following pulmonary arterial hypertension subjects upto 24 months
Group II: end-stage pulmonary hypertension .Experimental Treatment1 Intervention
subjects with end-stage PH that currently on the waitlist for lung transplant
129Xe Hyperpolarized is already approved in United States for the following indications:
🇺🇸 Approved in United States as Hyperpolarized 129Xe for:
- Pulmonary hypertension (investigational)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Duke University Medical CenterDurham, NC
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Who Is Running the Clinical Trial?
Bastiaan DriehuysLead Sponsor
References
Abnormalities in hyperpolarized (129)Xe magnetic resonance imaging and spectroscopy in two patients with pulmonary vascular disease. [2023]The diagnosis of pulmonary vascular disease (PVD) is usually based on hemodynamic and/or clinical criteria. Noninvasive imaging of the heart and proximal vasculature can also provide useful information. An alternate approach to such criteria in the diagnosis of PVD is to image the vascular abnormalities in the lungs themselves. Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) is a novel technique for assessing abnormalities in ventilation and gas exchange in the lungs. We applied this technique to two patients for whom there was clinical suspicion of PVD. Two patients who had significant hypoxemia and dyspnea with no significant abnormalities on computed tomography imaging or ventilation-perfusion scan and only mild or borderline pulmonary arterial hypertension at catheterization were evaluated. They underwent HP (129)Xe imaging and subsequently had tissue diagnosis obtained from lung pathology. In both patients, HP (129)Xe imaging demonstrated normal ventilation but markedly decreased gas transfer to red blood cells with focal defects on imaging, a pattern distinct from those previously described for idiopathic pulmonary fibrosis or obstructive lung disease. Pathology on both patients later demonstrated severe PVD. These findings suggest that HP (129)Xe MRI may be useful in the diagnosis of PVD and monitoring response to therapy. Further studies are required to determine its sensitivity and specificity in these settings.
In vivo MR imaging of pulmonary perfusion and gas exchange in rats via continuous extracorporeal infusion of hyperpolarized 129Xe. [2021]Hyperpolarized (HP) (129)Xe magnetic resonance imaging (MRI) permits high resolution, regional visualization of pulmonary ventilation. Additionally, its reasonably high solubility (>10%) and large chemical shift range (>200 ppm) in tissues allow HP (129)Xe to serve as a regional probe of pulmonary perfusion and gas transport, when introduced directly into the vasculature. In earlier work, vascular delivery was accomplished in rats by first dissolving HP (129)Xe in a biologically compatible carrier solution, injecting the solution into the vasculature, and then detecting HP (129)Xe as it emerged into the alveolar airspaces. Although easily implemented, this approach was constrained by the tolerable injection volume and the duration of the HP (129)Xe signal.
Quantitative 129Xe MRI detects early impairment of gas-exchange in a rat model of pulmonary hypertension. [2021]Hyperpolarized 129Xe magnetic resonance imaging (MRI) is capable of regional mapping of pulmonary gas-exchange and has found application in a wide range of pulmonary disorders in humans and animal model analogs. This study is the first application of 129Xe MRI to the monocrotaline rat model of pulmonary hypertension. Such models of preclinical pulmonary hypertension, a disease of the pulmonary vasculature that results in right heart failure and death, are usually assessed with invasive procedures such as right heart catheterization and histopathology. The work here adapted from protocols from clinical 129Xe MRI to enable preclinical imaging of rat models of pulmonary hypertension on a Bruker 7 T scanner. 129Xe spectroscopy and gas-exchange imaging showed reduced 129Xe uptake by red blood cells early in the progression of the disease, and at a later time point was accompanied by increased uptake by barrier tissues, edema, and ventilation defects-all of which are salient characteristics of the monocrotaline model. Imaging results were validated by H&E histology, which showed evidence of remodeling of arterioles. This proof-of-concept study has demonstrated that hyperpolarized 129Xe MRI has strong potential to be used to non-invasively monitor the progression of pulmonary hypertension in preclinical models and potentially to also assess response to therapy.
Functional airway obstruction observed with hyperpolarized 129 Xenon-MRI. [2022]Hyperpolarized 129 Xenon-MRI (HP 129 Xe MRI) is an emerging imaging modality that allows assessment of both ventilation and gas transfer. Most research to date has focused on non-malignant pulmonary diseases. However, the capability of evaluating the two primary physiological processes of the lung (ventilation and gas transfer) makes HP 129 Xe MRI a promising imaging modality in the management of patients with lung cancer.
Brain Imaging Using Hyperpolarized 129Xe Magnetic Resonance Imaging. [2019]Hyperpolarized (HP) 129Xe magnetic resonance imaging (MRI) is a novel iteration of traditional MRI that relies on detecting the spins of 1H. Since 129Xe is a gaseous signal source, it can be used for lung imaging. Additionally, 129Xe dissolves in the blood stream and can therefore be detectable in the brain parenchyma and vasculature. In this work, we provide detailed information on the protocols that we have developed to image 129Xe within the brains of both rodents and human subjects.
Development of hyperpolarized noble gas MRI. [2019]Magnetic resonance imaging using the MR signal from hyperpolarized noble gases 129Xe and 3He may become an important new diagnostic technique. Alex Pines (adapting the hyperpolarization technique pioneered by William Happer) presented MR spectroscopy studies using hyperpolarized 129Xe. The current authors recognized that the enormous enhancement in the delectability of 129Xe, promised by hyperpolarization, would solve the daunting SNR problems impeding their attempts to use 129Xe as an in vivo MR probe, especially in order to study the action of general anesthetics. It was hoped that hyperpolarized 129Xe MRI would yield resolutions equivalent to that achievable with conventional 1H2O MRI, and that xenon's solubility in lipids would facilitate investigations of lipid-rich tissues that had as yet been hard to image. The publication of hyperpolarized 129Xe images of excised mouse lungs heralded the emergence of hyperpolarized noble-gas MRI. Using hyperpolarized 3He, researchers have obtained images of the lung gas space of guinea pigs and of humans. Lung gas images from patients with pulmonary disease have recently been reported. 3He is easier to hyperpolarize than 129Xe, and it yields a stronger MR signal, but its extremely low solubility in blood precludes its use for the imaging of tissue. Xenon, however, readily dissolves in blood, and the T1, of dissolved 129Xe is long enough for sufficient polarization to be carried by the circulation to distal tissues. Hyperpolarized 129Xe dissolved-phase tissue spectra from the thorax and head of rodents and humans have been obtained, as have chemical shift 129 Xe images from the head of rats. Lung gas 129Xe images of rodents, and more recently of humans, have been reported. Hyperpolarized 129Xe MRI (HypX-MRI) may elucidate the link between the structure of the lung and its function. The technique may also be useful in identifying ventilation-perfusion mismatch in patients with pulmonary embolism, in staging and tracking the success of therapeutic approaches in patients with chronic obstructive airway diseases, and in identifying candidates for lung transplantation or reduction surgery. The high lipophilicity of xenon may allow MR investigations of the integrity and function of excitable lipid membranes. Eventually, HypX-MRI may permit better imaging of the lipid-rich structures of the brain. Cortical brain function is one perfusion-dependent phenomena that may be explored with hyperpolarized 129Xe MR. This leads to the exciting possibility of conducting hyperpolarized 129Xe functional MRI (HypX-fMRI) studies.
Repeatability of regional pulmonary functional metrics of Hyperpolarized 129 Xe dissolved-phase MRI. [2020]Label="BACKGROUND">MRI of hyperpolarized 129 Xenon (HP 129 Xe) is increasingly utilized for investigating pulmonary function. The solubility of HP 129 Xe in lung tissue, blood plasma (Barrier), and red blood cells (RBC), with unique chemical shifts, enables spectroscopic imaging of potential imaging biomarkers of gas exchange and microstructural pulmonary physiology.