Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH)

Recruiting

• Conditions: Idiopathic Pulmonary Arterial Hypertension; Heritable Pulmonary Arterial Hypertension; Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
• Interventions: Other: No Intervention

• Registration Number: NCT05462574
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The investigators propose to study the relationship between right ventricle (RV) steatosis and RV function, exercise capacity, and outcomes in humans with pulmonary arterial hypertension (PAH) and to identify potential drivers of lipid accumulation.

Detailed Description

The investigators propose to test the hypothesis that abnormal lipid metabolism in PAH leads to delivery of fatty acids in excess of RV oxidative capacity, resulting in steatosis and lipotoxicity. The objectives of the study are to: 1) Define the relationships between RV steatosis, RV function, and exercise capacity; 2) Identify mechanistic drivers of RV steatosis including BMPR2 expression and lipid metabolism; 3) Examine lipid metabolism in PAH skeletal muscle as a potential driver of reduced functional capacity.

In Aim 1 (clinical relevance) the investigators will measure RV and left ventricle (LV) lipid in participants with heritable, idiopathic, and scleroderma- associated PAH. Participants will undergo the 6-minute walk test, cardiopulmonary exercise testing, and will be followed for clinical events. A subgroup will undergo repeat MRS at four timepoints over three years to determine the natural history of steatosis.

In Aim 2 (mechanism), the investigators will perform metabolomic/lipidomic profiling of peripheral and coronary sinus plasma and measure BMPR2 expression to identify potential drivers of steatosis.

In Aim 3 (specificity), the investigators will perform MRS on skeletal muscle in Aim 1 participants and matched healthy controls to clarify the systemic effects of lipid metabolic defects in PAH.

Study Timeline

• Study First Submitted: 2022-07-14
• Study First Submitted QC: 2022-07-14
• Study First Posted: 2022-07-18
• Study Start: 2023-01-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-13
• Last Update Posted: 2025-05-16
• Primary Completion: 2027-09-30
• Study Completion: 2027-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 75

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Participants with Pulmonary Arterial Hypertension (PAH)	No Intervention	Participants with heritable, idiopathic, and scleroderma associated PAH.

Primary Outcome Measures

Name	Time	Method
Change in Right Ventricular (RV) Ejection Fraction	Baseline to 36 months	Change in RV ejection fraction will be measured by cardiac MRI.
Change in Right Ventricular (RV) Lipid Content	Baseline to 36 months	Change in RV lipid content will be measured by cardiac proton magnetic resonance spectroscopy (MRS). Lipid content is expressed as a percent of the voxel occupied by lipid.
Ratio of BMPR2 isoform B/A.	Baseline to 36 months	BMPR2 isoforms A and B and wild type gene expression will be measured by real-time polymerase chain reaction (PCR) and validated by measuring protein content using Western blot test.
Change in skeletal muscle lipid content.	Baseline to 36 months	Change in skeletal muscle lipid content will be measured by skeletal muscle proton MRS. Lipid content is expressed as percent triglyceride (%TG)
Identification of metabolic markers (dihyroxybutyrate, acetylputriscene, hydroxystearate and glucuronate) in the peripheral circulation and coronary sinus.	Baseline to 36 months	Metabolite markers will be measured by ultrahigh performance liquid chromatography and mass spectrometry.

Trial Locations

Locations (1)

Vanderbilt University Medical Center; 🇺🇸 Nashville, Tennessee, United States