Defining a Noninvasive Signature for Pulmonary Vascular Remodeling in Group 3 PH

Bastiaan Driehuys2 个研究点分布在 1 个国家目标入组 30 人开始时间: 2023年11月8日最近更新: 2026年2月24日

适应症

干预措施

试验速览

阶段: 2 期
状态: 招募中
发起方
入组人数: 30
试验地点: 2
主要终点: a pathology-based 129Xe MRI noninvasive signature of pulmonary vascular remodeling that could be validated in a larger cohort of Group 3 PH patients

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The main goal of this study is to develop a noninvasive signature for pulmonary vascular remodeling in Group 3 PH patients, using hyperpolarized 129Xe magnetic resonance imaging (129Xe MRI). Such a signature may identify Group 3 PH responders to PAH-specific therapies. PAH's unique 129Xe MRI signature has been shown in previous studies. Past studies have lacked a pathologic "ground truth" correlate of these signatures, which could be provided by comparing them with the pathology of lung explant tissue from patients who have undergone a lung transplant. This signature could be validated in a cohort of patients with Group 3 PH in future studies.

详细描述

The objective of this study is to identify a 129Xe MRI signature associated with PAH-like pulmonary vascular remodeling, consisting of plexiform arteriopathy, smooth muscle cell proliferation, and vascular fibrosis, in IPF and COPD that could be used to identify potential responders vs non-responders to PAH-specific therapies. The central hypothesis is that similar mechanisms and pathways underlie pulmonary vascular remodeling in IPF-PH, COPD-PH, and PAH. However, only a subset of Group 3 PH patients display remodeling consistent with PAH, resulting in responder vs. non-responder phenotypes when treated with PAH-specific therapies. In preliminary studies of subjects treated with Tyvaso, The study team has observed distinct 129Xe MRI signatures at baseline and with therapy depending on patients' underlying lung function. Consistent with this, recent studies using single-cell RNA sequencing (scRNAseq) of the pulmonary vasculature in IPF have demonstrated changes consistent with vascular remodeling.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Diagnostic
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Age ≥ 18 years' old
•Be on the lung transplant waiting list at Duke University Medical Center.
•PH as defined by RHC - mPAP > 20 mmHg, PVR > 3 WU, PCWP < 15 mmHg
•Groups defined as:
•PAH: Clinical diagnosis of PAH (Group 1 PH) in the absence of severe chronic lung disease, left heart disease, chronic thromboembolism, sarcoidosis, sickle cell disease, or other causes of non-Group 1 PH.
•COPD-noPH: Clinical diagnosis of COPD in the absence of precapillary PH.
•COPD-PH: Clinical diagnosis of COPD with precapillary PH.
•IPF-noPH: Clinical diagnosis of IPF in the absence of precapillary PH.
•IPF-PH: Clinical diagnosis of IPF with precapillary PH.
•Willing and able to give informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed).

排除标准

•Moderate to severe heart disease (LVEF < 45% or severe LV Hypertrophy).
•Sarcoidosis.
•Active cancer.
•Sickle cell anemia.
•Liver disease (Childs-Pugh class C).
•Prisoners and pregnant women will not be approached for the study.
•Inability to obtain consent.
•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

PAH:

Experimental

Clinical diagnosis of PAH (Group 1 PH) in the absence of severe chronic lung disease, left heart disease, chronic thromboembolism, sarcoidosis, sickle cell disease or other causes of non-Group 1 PH.