129 Xenon MRI as a Biomarker for Diagnosis and Response to Therapy in Pulmonary Arterial Hypertension (PAH) (Xenon PAH Bio)

The overall study objectives outlined in this study are to derive 129Xe MRI pulmonary vascular biomarker signatures that differentiate common subtypes of PAH and to determine the ability of 129Xe MRI to longitudinally monitor disease progression and response to therapy in PAH, with the aid of additional assessments, such as labs, echocardiography, and six-minute walk distance (6MWD).

Study Overview

• Status: Not yet recruiting
• Conditions: Connective Tissue Diseases; Pulmonary Arterial Hypertension; Idiopathic Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension Associated With Connective Tissue Disease (Disorder)
• Intervention / Treatment: Drug: 129Xe Hyperpolarized

Detailed Description

Subject Enrollment This study will consent and enroll 20 subjects total.

• For Arm 1, 10 subjects with Idiopathic Pulmonary Arterial Hypertension (IPAH) will be consented and enrolled. For Arm 2, 10 subjects with Connective Tissue Disease Associated Pulmonary Arterial Hypertension (PAH-CTD) will be consented and enrolled.

Study Design This study will be observational. Subjects in both arms of the trial will undergo a 129Xe MRI/MRS at timepoints of baseline, 3 months, 6 months, and 12 months. In addition to the this, data from standard of care assessments, such as labs, echocardiography, and six-minute walk distance (6MWD), will also collected at these timepoints.

Primary Study Endpoints The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months

Secondary Study Endpoints

There will be several secondary endpoints for this trial:

• Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months
• Change in 6MWD from baseline to 12 months
• Change in NTproBNP from baseline to 12 months
• Change in WHO FC from baseline to 12 months

Primary Safety Endpoints

There will be several primary safety endpoints for this trial:

• Frequency of Adverse Events (AE) and/or Serious Adverse Events (SAE)
• Withdrawals due to adverse event or death
• Incidence of Adverse Events of Significant Interest (AESI):
• Electrocardiogram and any findings
• Physical examination and vital signs

• Study Type: Interventional
• Enrollment (Estimated): 20
• 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
      • Duke University Medical Center
      • Contact: David Ptashnik; Phone Number: 919-668-2642; Email: david.ptashnik@duke.edu
      • Principal Investigator: Fawaz A Alenezi, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Arm 1 -IPAH

• Age: 18-75 years
• WHO functional class 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 Wood Units (WU)
• No other cause identified for PAH

Arm 2 -PAH-CTD

• Age: 18-75 years
• WHO functional class (FC) 2 or 3
• Mean pulmonary artery pressures > 20 mmHg
• Pulmonary capillary wedge pressure ≤15 mmHg
• Pulmonary vascular resistance > 2 WU
• Diagnosis of connective tissue disease

Exclusion Criteria:

• PH other than Idiopathic PAH or PAH associated with CTD; any conditions that prevent the performance of 129Xe MRI scans will be excluded from the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Idiopathic Pulmonary Arterial Hypertension; Arm 1... patients with IPAH	Drug: 129Xe Hyperpolarized; Each xenon dose will be limited to a volume less than 25% of a subject's total lung capacity (TLC), as is the case for all protocols currently carried out under IND 109490
Other: Pulmonary Arterial Hypertension Associated with Connective Tissue Disease; Arm 2... patients with CTD-PAH	Drug: 129Xe Hyperpolarized; Each xenon dose will be limited to a volume less than 25% of a subject's total lung capacity (TLC), as is the case for all protocols currently carried out under IND 109490

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Vascular Remodeling	The primary endpoint for this trial will be the change in defect + low percentage of RBC signal on hyperpolarized 129Xe MRI from baseline to 12 months	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RBC Oscillation Amplitude	• Change in regional and global RBC Oscillation Amplitudes on hyperpolarized 129Xe MR spectroscopy from baseline to 12 months	1 year
6 Minute Walk Distance	Change in 6MWD from baseline to month 12	1 Year
NTproBNP	Change in NTproBNP from baseline to month 12	1 year
World Health Organization (WHO) Functional Class (FC)	Change in WHO FC from baseline to month 12	1 year

Collaborators and Investigators

• Sponsor: Bastiaan Driehuys
• Collaborators: American Heart Association
• Investigators: Principal Investigator: Fawaz Alenezi, MD, Duke Univeristy

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2024
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): March 31, 2026

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 20, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Hypertension; Disease; Pulmonary Arterial Hypertension; Familial Primary Pulmonary Hypertension; Connective Tissue Diseases
• Other Study ID Numbers: Pro00113893

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