Xenon MRI in Pulmonary Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- pulmonary vascular remodeling
研究概览
简要总结
The overall objective outlined in this study is to determine how pulmonary vascular remodeling in PAH at a cellular and pathological level is associated with changes in gas exchange physiology and hemodynamics (monitored with 129Xe MRI/MRS) and how these signals change with disease progression or treatment.
详细描述
In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the team will hypothesize are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects
In aim 3, The study team will test whether directly monitoring lung pathology with 129Xe MRI will provide additional prognostic information to standard-of-care clinical monitoring in 45 subjects (cohort 2). At 6-month follow-up appointments, standard-of-care assessments including labs, echocardiography, and six-minute walk distance and 129Xe MRI will be collected. The study team expect that In aim 1, the study team will compare 129Xe MRI signatures to lung explant pathology, cellular identity from single-cell RNA sequencing, and cellular phenotypes in gas exchange defects to areas that are spared, which the study team hypothesizes are exposed to lower levels of hemodynamic shear stress. This will be done by performing 129Xe MRI scans in fifteen subjects (cohort 1) with PAH awaiting a lung transplant, followed by a pathologic assessment (with usual histopathology and single-cell RNA sequencing) of the subject's explanted lung after transplant. The study team expect that areas of proliferation and fibrosis will correlate with 129Xe MRI gas exchange and spectroscopic defects
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •of Cohort 1
- •Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
- •Outpatients of either gender, Age 18-75
- •Awaiting a lung transplant
- •Diagnosis of precapillary PH (right heart catheterization demonstrating hemodynamic criteria of a mean pulmonary artery pressure (mPAP) ≥ 25 mmHg, pulmonary vascular resistance ≥ 3 WU, pulmonary capillary wedge pressure ≤ 15 mmHg) in the setting of Group 1 (PAH), 3 (PH due to chronic lung disease, 4 (PH due to pulmonary artery obstructions), or 5 (PH due to miscellaneous causes)
- •Willing and giving 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 before MRI
排除标准
- •of Cohort 1
- •Subjects presenting with any of the following will not be included in the trials:
- •Moderate to severe heart disease (LVEF <45%, Severe LV hypertrophy, Moderate to severe valvular disease)
- •PH due to schistosomiasis
- •Active cancer
- •Sickle cell anemia
- •Prisoners and pregnant women will not be approached for the study
- •Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine)
- •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
- •Inclusion Criteria of Cohort 2
- •Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the trial:
- •Treatment naïve or treatment started within the last 3 months
- •Outpatients of either gender, Age 18-75
- •WHO functional class (FC) 2-3 symptoms with a diagnosis of group 1 PH (mean pulmonary artery pressures (mPAP) > 20 mmHg, pulmonary capillary wedge pressure (PCWP) ≤ 15mmHg and pulmonary vascular resistance (PVR) ≥3 WU)
- •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 before MRI
- •Exclusion Criteria of Cohort 2
- •Subjects presenting with any of the following will not be included in the trials:
- •Sarcoidosis
- •Active cancer
- •Sickle cell anemia
- •Liver disease (Childs-Pugh class C)
- •Any conditions that prevent the performance of 129Xe MRI scans.
- •Prisoners and pregnant women will not be approached for the study.
- •Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine).
- •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
研究组 & 干预措施
end-stage pulmonary hypertension .
subjects with end-stage PH that currently on the waitlist for lung transplant
干预措施: 129Xe Hyperpolarized (Drug)
following pulmonary arterial hypertension subjects
Following pulmonary arterial hypertension subjects upto 24 months
干预措施: 129Xe Hyperpolarized (Drug)
结局指标
主要结局
pulmonary vascular remodeling
时间窗: 5 years
The study team will determine whether the correlation between Red Blood Cell Signal from Xenon MRI to pathologic scoring of pulmonary vascular remodeling from histopathology is statistically significant.
Red Blood Cell Signal from Xenon MRI
时间窗: 5 years
We will determine whether the correlation between Red Blood Cell Signal from Xenon MRI to six minute walk distance, tricuspid annular plane excursion and right ventricular systolic pressure in longitudinal follow-up of PAH patients is statistically significant.
次要结局
未报告次要终点
研究者
Bastiaan Driehuys
Associate Professor of Radiology
Duke University