Pulmonary Hypertension SOLAR (PH SOLAR)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Pulmonary Arterial Hypertension; Interstitial Lung Disease; COPD
• Intervention / Treatment: Drug: Hyperpolarized 129Xe

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.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: David Ptashnik, MS; Phone Number: 919-668-2642; Email: david.ptashnik@duke.edu

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Contact: David Ptashnik, MS; Phone Number: 919-668-2642; Email: david.ptashnik@duke.edu
      • Principal Investigator: Sudarshan Rajagopal, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Hyperpolarized 129Xe; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI
Experimental: COPD-noPH; Clinical diagnosis of COPD in the absence of precapillary PH.	Drug: Hyperpolarized 129Xe; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI
Experimental: COPD-PH; Clinical diagnosis of COPD with precapillary PH	Drug: Hyperpolarized 129Xe; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI
Experimental: IPF-noPH; Clinical diagnosis of IPF in the absence of precapillary PH	Drug: Hyperpolarized 129Xe; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI
Experimental: IPF-PH; Clinical diagnosis of IPF with precapillary PH	Drug: Hyperpolarized 129Xe; Each xenon dose will be limited to a volume less than 25% of subject lung capacity (TLC),; Other Names: Xe MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
a pathology-based 129Xe MRI noninvasive signature of pulmonary vascular remodeling that could be validated in a larger cohort of Group 3 PH patients	Such a signature could then be tested in clinical trials in Group 3 PH. These studies will have an important positive impact because they lay the foundation for a precision medicine strategy in Group 3 PH through the identification of potential responders and non-responders to PAH-specific therapies	2 yrs

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Investigators: Principal Investigator: Sudarshan Rajagopal, MD, PhD, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): November 8, 2023
• Primary Completion (Estimated): December 30, 2024
• Study Completion (Estimated): December 30, 2024

Study Registration Dates

• First Submitted: February 26, 2021
• First Submitted That Met QC Criteria: February 26, 2021
• First Posted (Actual): March 2, 2021

Study Record Updates

• Last Update Posted (Actual): January 18, 2024
• Last Update Submitted That Met QC Criteria: January 16, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Lung Transplant; Group 3 PH
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary; Hypertension; Lung Diseases; Pulmonary Arterial Hypertension; Lung Diseases, Interstitial
• Other Study ID Numbers: Pro00106221

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No