Clinical trial NCT04778046: Pulmonary Hypertension SOLAR
Official title: Defining a Noninvasive Signature for Pulmonary Vascular Remodeling in Group 3 PH
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Interstitial Lung Disease
COPD
Pulmonary Arterial Hypertension
Keywords: Lung Transplant
Group 3 PH
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2021-03-02
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years' old
2. Be on the lung transplant waiting list at Duke University Medical Center.
3. PH as defined by RHC - mPAP \> 20 mmHg, PVR \> 3 WU, PCWP \< 15 mmHg
4. 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.
5. Willing and able to give informed consent and adhere to visit/protocol schedules (consent must be given before any study procedures are performed).

Exclusion Criteria:

1. Moderate to severe heart disease (LVEF \< 45% or severe LV Hypertrophy).
2. Sarcoidosis.
3. Active cancer.
4. Sickle cell anemia.
5. Liver disease (Childs-Pugh class C).
6. Prisoners and pregnant women will not be approached for the study.
7. Inability to obtain consent.
8. Conditions that will prohibit MRI scanning (metal in eye, claustrophobia, inability to lie supine).
9. 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

Primary outcomes:
measure: a pathology-based 129Xe MRI noninvasive signature of pulmonary vascular remodeling that could be validated in a larger cohort of Group 3 PH patients
timeFrame: Day 1
Secondary outcomes:
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: Sudarshan Rajagopal, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: