Idiopathic Pulmonary Arterial HypertensionNCT05462574
Right Ventricle Lipid in Pulmonary Arterial Hypertension (PAH)
An observational study of Idiopathic Pulmonary Arterial Hypertension and Heritable Pulmonary Arterial Hypertension, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
- How many people
- 75 participants
- Where
- 1 siteUnited States
- Study dates
- 17 Jan 2023to 30 Sep 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with PAH will be recruited from the Center for Pulmonary Vascular Disease (CPVD) at Vanderbilt University Medical Center.
Who may be able to join
- ≥ 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Clinical and Mechanistic Understanding of Right Ventricular Steatosis 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.
Read the 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.
- Conditions
- Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
- Being tested
- No Intervention
- Medical subject headings
- Familial Primary Pulmonary Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
No InterventionOther
No Intervention
| Study group | Role | What they receive |
|---|---|---|
| Participants with Pulmonary Arterial Hypertension (PAH) | Participants with heritable, idiopathic, and scleroderma associated PAH. Receives: Other: No Intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Right Ventricular (RV) Ejection Fraction
Change in RV ejection fraction will be measured by cardiac MRI.
Measured: Baseline to 36 months
Change in Right Ventricular (RV) Lipid Content
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.
Measured: Baseline to 36 months
Identification of metabolic markers (dihyroxybutyrate, acetylputriscene, hydroxystearate and glucuronate) in the peripheral circulation and coronary sinus.
Metabolite markers will be measured by ultrahigh performance liquid chromatography and mass spectrometry.
Measured: Baseline to 36 months
Ratio of BMPR2 isoform B/A.
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.
Measured: Baseline to 36 months
Change in skeletal muscle lipid content.
Change in skeletal muscle lipid content will be measured by skeletal muscle proton MRS. Lipid content is expressed as percent triglyceride (%TG)
Measured: Baseline to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jul 2022
- Study start17 Jan 2023
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Sep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Pulmonary Arterial HypertensionStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 75 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Evan Brittain, Vanderbilt University Medical Center
- Investigators
- Evan Brittain, MD, MSCI, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05462574
- Sponsor's protocol ID
- 221138
- Other IDs
- HL155278
- Status last verified
- May 2026
- First submitted
- 14 Jul 2022
- Last updated
- 29 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Clinical and Mechanistic Understanding of Right Ventricular Steatosis in Pulmonary Arterial Hypertension (PAH)
- ClinicalTrials.gov ID
- NCT05462574
- Acronym / sponsor ID
- 221138
- Conditions
- Idiopathic Pulmonary Arterial Hypertension, Heritable Pulmonary Arterial Hypertension, Pulmonary Arterial Hypertension Associated With Connective Tissue Disease
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 75 participants (estimated)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- 17 Jan 2023 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 18 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Participants with Pulmonary Arterial Hypertension (PAH) | – | Other: No InterventionParticipants with heritable, idiopathic, and scleroderma associated PAH. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with PAH will be recruited from the Center for Pulmonary Vascular Disease (CPVD) at Vanderbilt University Medical Center.
Key inclusion criteria (6 listed)
- ≥ 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
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| No InterventionNo Intervention | Other | Participants with Pulmonary Arterial Hypertension (PAH) |
Primary outcome
Change in Right Ventricular (RV) Ejection Fraction
Time frame: Baseline to 36 months
Change in RV ejection fraction will be measured by cardiac MRI.
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.
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.
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.
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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Evan Brittain, MD, MSCI principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Idiopathic Pulmonary Arterial Hypertension and Heritable Pulmonary Arterial Hypertension, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Natasha Billard ((434) 851-3306, natasha.billard.1@vumc.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Right Ventricular (RV) Ejection Fraction (time frame: Baseline to 36 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.