Metabolic Remodeling in Pulmonary Arterial Hypertension (PAH)

NCT04968210 | Completed

• 1 other identifier: STU-2020-1351
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Pulmonary arterial hypertension (PAH) is a progressive disease in which clinically relevant symptoms present a few years after the onset in rise of pulmonary arterial pressure. Increased PA pressure presents an overload on the right ventricle (RV), with RV failure being a common cause of mortality in PAH. Current therapeutic targets help reduce vascular resistance and RV afterload, however, RV dysfunction may continue to progress. Therefore, the reason for RV failure in PAH cannot be contributed to altered vascular hemodynamics alone but may be related to metabolic alterations and failure of adaptive mechanisms in the RV. Providing a better understanding of metabolic remodeling in RV failure may permit the development of RV-targeted pharmacological agents to maintain RV function despite increased pulmonary vascular pressures. This study will evaluate how cardiac metabolism changes in response to pulmonary vasodilator therapy in patients with pulmonary arterial hypertension.

Conditions

Pulmonary Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• Change in ratio of oxidative metabolism to glycolysis

  Ratio of bicarbonate to lactate area under the curve, as a measure of oxidative metabolism relative to glycolysis, respectively. The ratio will be compared before and after 6 months of standard of care pulmonary vasodilator therapy in PAH patients.

  Baseline, 6 months

Study Arms (1)

Pulmonary arterial hypertension (PAH)

Patients that have been clinically diagnosed with pulmonary arterial hypertension and fall under the category of WHO group 1 PAH.

Drug: Hyperpolarized 13C-pyruvate

Interventions

Hyperpolarized 13C-pyruvate DRUG

Use of hyperpolarized 13C-pyruvate to assess metabolic remodeling in PAH

Pulmonary arterial hypertension (PAH)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

WHO group 1 PAH, characterized by mean pulmonary artery pressure ≥25 mmHg, PVR \>3 Woods units, and pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≤15 mmHg. Participants must be further classified as idiopathic PAH (IPAH) or connective tissue disease associated PAH (CTD-PAH).

You may qualify if:

• WHO group 1 PAH, characterized by mean pulmonary artery pressure ≥25 mmHg, PVR \>3 Woods units, and pulmonary capillary wedge pressure or left ventricular end diastolic pressure ≤15 mmHg. Participants must be further classified as idiopathic PAH (IPAH) or connective tissue disease associated PAH (CTD-PAH).
• New York Heart Association (NYHA) classification I - III criteria of heart failure.
• Vasodilator therapy naïve, with the intent to initiate pulmonary vasodilator therapy.
• Age 18 - 75.
• English speaking and able to provide informed consent.

You may not qualify if:

• Recent syncope.
• Baseline 6MWD \< 400 feet or NYHA class IV heart failure.
• Metabolic disorders such as uncontrolled diabetes (A1c \> 8%) that may alter cardiac metabolism.
• Baseline use of oral steroids.
• FEV1/FVC \<60%
• Contraindications to MRI, including those noted on the UTSW MRI Screening Form such as implants contraindicated at 3T, pacemakers, Implantable Cardioverter Defibrillators (ICD), or significant claustrophobia.
• Weight \>210 lbs (exceeds current IND weight-based dosing guidelines) 8 . Women who are pregnant, lactating or planning on becoming pregnant during the study.
• \. Not suitable for study participation due to other reasons at the discretion of the investigators

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Pulmonary Arterial Hypertension

Condition Hierarchy (Ancestors)

Hypertension, Pulmonary; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Kara Goss, MD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine and Pediatrics

Study Record Dates

• First Submitted: July 7, 2021
• First Posted: July 20, 2021
• Study Start: May 27, 2022
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: January 13, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)