Pulmonary Hypertension SOLAR (PH SOLAR)

• ClinicalTrials.gov Identifier: NCT04778046
• Recruitment Status: Recruiting
• First Posted: March 2, 2021
• Last Update Posted: April 11, 2023
• Sponsor: Bastiaan Driehuys
• Information provided by (Responsible Party): Bastiaan Driehuys, Duke University

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Interstitial Lung Disease; COPD; Pulmonary Arterial Hypertension	Drug: Hyperpolarized 129Xe	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Defining a Noninvasive Signature for Pulmonary Vascular Remodeling in Group 3 PH
• Estimated Study Start Date: May 15, 2023
• Estimated Primary Completion Date: August 30, 2023
• Estimated Study Completion Date: August 30, 2023

Arms and Interventions

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 Name: 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 Name: 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 Name: 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 Name: 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 Name: Xe MRI

Outcome Measures

Primary Outcome Measures :

1. a pathology-based 129Xe MRI noninvasive signature of pulmonary vascular remodeling that could be validated in a larger cohort of Group 3 PH patients [ Time Frame: 2 yrs ]
   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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: David Ptashnik, MS; 919-668-2642; david.ptashnik@duke.edu

Locations

United States, North Carolina

Duke University Medical Center; Recruiting

Durham, North Carolina, United States, 27710

Contact: David Ptashnik, MS 919-668-2642 david.ptashnik@duke.edu

Principal Investigator: Sudarshan Rajagopal, MD, PhD

Sponsors and Collaborators

Bastiaan Driehuys

Investigators

• Principal Investigator: Sudarshan Rajagopal, MD, PhD; Duke University

More Information

• Responsible Party: Bastiaan Driehuys, Associate Professor of Radiology, Duke University
• ClinicalTrials.gov Identifier: NCT04778046
• Other Study ID Numbers: Pro00106221
• First Posted: March 2, 2021
• Last Update Posted: April 11, 2023
• Last Verified: April 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Bastiaan Driehuys, Duke University:

Lung Transplant; Group 3 PH

Additional relevant MeSH terms:

Lung Diseases; Pulmonary Arterial Hypertension; Lung Diseases, Interstitial; Hypertension; Vascular Diseases; Cardiovascular Diseases; Respiratory Tract Diseases; Hypertension, Pulmonary