Right Ventricular Metabolism in Pulmonary Arterial Hypertension

Completed

• Conditions: Pulmonary Arterial Hypertension; Healthy

• Registration Number: NCT02763735
• Lead Sponsor: Vanderbilt University Medical Center

Brief Summary

The purpose of this study is to use non-invasive imaging to determine the metabolic phenotype of the right ventricle in patients with pulmonary arterial hypertension across a spectrum of disease severity.

Detailed Description

Current medical therapy for pulmonary arterial hypertension (PAH) is aimed at reducing pulmonary vascular resistance (PVR) but not ameliorating right ventricular (RV) failure, the major cause of death. There are no RV-specific therapies currently available for PAH, in part because the pathophysiology of RV failure is poorly understood.

The investigators hypothesize that the RV in PAH develops a distinct metabolic pattern characterized by increased glycolysis, impaired oxidative metabolism and lipid deposition, which are associated with RV failure.

Specific Aim 1. To test the hypothesis that the RV in human PAH exhibits lipid deposition, increased glycolysis and impaired fatty acid oxidation. The investigators will measure RV oxidative metabolism and glycolysis in PAH patients and controls using positron emission tomography 11C acetate and \[18F\]fluoro-deoxy-D-glucose imaging and measure myocardial lipid accumulation using magnetic resonance spectroscopy imaging.

Specific Aim 2. To test the hypothesis that an abnormal RV metabolic profile is associated with RV dysfunction and reduced exercise capacity in PAH. PET and MRS findings will be correlated with RV function, patient exercise capacity and a blood metabolic profile.

Study Timeline

• Study Start: 2014-06
• Study First Submitted: 2016-04-28
• Study First Submitted QC: 2016-05-03
• Study First Posted: 2016-05-05
• Primary Completion: 2019-06
• Study Completion: 2019-06
• Status Verified: 2020-05
• Last Update Submitted: 2020-05-18
• Last Update Posted: 2020-05-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• Heritable or idiopathic PAH
• 18 years or older
• Able to give informed consent

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Exclusion Criteria

• Pregnancy
• Type 1 diabetes mellitus
• Prednisone use
• PAH associated with any condition other than idiopathic or heritable
• Implanted ferromagnetic material incompatible with MRI

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Right ventricular oxygen consumption divided by the rate pressure product	At time of C11 acetate PET scan	kmono divided by the rate pressure product (heart rate X systolic blood pressure)

Secondary Outcome Measures

Name	Time	Method
Right ventricular oxygen consumption (kmono)	At time of C11 acetate PET scan
Right ventricular glucose uptake (standardized uptake value)	At time of 18-FDG PET scan
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with plasma metabolic profile	Day 1
Percent myocardial triglyceride content	At time of cardiac magnetic resonance imaging	Percent of myocardial triglyceride measured in the interventricular septum
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with right ventricular function	Day 1
Correlation of kmono, kmono/RPP, FDG uptake, and myocardial triglyceride content with six minute walk distance	Day 1

Trial Locations

Locations (1)

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