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NCT Number: NCT05462574

Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH)

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.

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Key information

Conditions

Idiopathic Pulmonary Arterial Hypertension Familial Primary Pulmonary Hypertension Heritable Pulmonary Arterial Hypertension Hypertension, Pulmonary Lung Diseases Pulmonary Arterial Hypertension Associated With Connective Tissue Disease Respiratory Tract Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location status: Recruiting

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ≥ 18 years old
  • Diagnosed with idiopathic, heritable, connective tissue disease-associated PAH, associated pulmonary arterial hypertension (PAH), or drug-or toxin-associated PAH according to World Health Organization (WHO) consensus recommendations.
  • Stable PAH-specific medication regimen for three months prior to enrollment. Adjustments in IV prostacyclin for side effect management are allowed. Diuretic adjustments are permitted.
  • WHO Functional Class I-III
  • Ambulatory
  • Able to have an MRI/MRS, perform a 6MWD test, and cardiopulmonary exercise test

Exclusion criteria

  • Pregnancy
  • Diagnosis of PAH etiology other than idiopathic, heritable, connective tissue disease - associated PAH or associated with drugs and toxins
  • WHO Functional class IV heart failure
  • Requirement for continuous oxygen
  • Unable to have an MRI/MRS, perform a 6MWD test, or cardiopulmonary exercise test.
  • Patients with implanted/embedded ferromagnetic material that would preclude cardiac MRI

Treatment and study plan

No intervention

Other

No Intervention

Primary outcomes

  1. Change in Right Ventricular (RV) Ejection Fraction

    Time frame: Baseline to 36 months

    Change in RV ejection fraction will be measured by cardiac MRI.

  2. Change in Right Ventricular (RV) Lipid Content

    Time frame: 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.

  3. Identification of metabolic markers (dihyroxybutyrate, acetylputriscene, hydroxystearate and glucuronate) in the peripheral circulation and coronary sinus.

    Time frame: Baseline to 36 months

    Metabolite markers will be measured by ultrahigh performance liquid chromatography and mass spectrometry.

  4. Ratio of BMPR2 isoform B/A.

    Time frame: 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.

  5. Change in skeletal muscle lipid content.

    Time frame: 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)

Study contacts

Contact information is provided by the study sponsor or research team.

Evan Brittain, MD, MSCI

CONTACT

[email protected]

(615) 322-4382

Natasha Billard

CONTACT

[email protected]

(434) 851-3306

Sponsors and collaborators

Lead sponsor

Vanderbilt University Medical Center

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

Clinical and Mechanistic Understanding of Right Ventricular Steatosis in Pulmonary Arterial Hypertension (PAH)

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Jul 18, 2022
Registry last updated
May 29, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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