Ignite Creation Date:
2024-05-06 @ 4:22 PM
Last Modification Date:
2024-10-26 @ 2:09 PM
Study NCT ID:
NCT04968210
Status:
RECRUITING
Last Update Posted:
2024-05-07
First Post:
2021-07-07
Brief Title:
Metabolic Remodeling in Pulmonary Arterial Hypertension PAH
Sponsor:
University of Texas Southwestern Medical Center
Organization:
University of Texas Southwestern Medical Center
Study Overview
Official Title:
Cardiac Metabolic Remodeling After Pulmonary Vasodilator Therapy in Pulmonary Arterial Hypertension A Pilot Study
Status:
RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
Detailed Description:
PAH is a silent progressive disease of the pulmonary vasculature that often presents clinically later in the course of disease Symptoms including severe shortness of breath present on average 2 years post onset as pulmonary arterial pressures rise due to elevated pulmonary vascular resistance PVR Elevated PVR causes right ventricular RV overload metabolic shifts and myocardial remodeling resulting in impaired RV contractility dysfunction and subsequent RV failure Right heart failure is a common cause of death in patients with PAH Currently all therapies for PAH target the pulmonary vasculature by improving pulmonary vasodilation and reducing vascular resistance There is limited direct effect on the myocardium although RV function generally improves with reduced afterload However despite reduction in PVR with vasodilators the resting RV dysfunction may ultimately progress in patients with PAH Thus the reason for RV failure cannot be completely attributed to the changes in pulmonary vascular hemodynamics but may also be related to metabolic shifts and failure of compensatory mechanisms in the RV A better understanding of how the RV myocardium remodels in RV failure from PAH and in response to pulmonary vasodilator therapy may allow for development of RV-targeted therapies to maintain RV function despite continually elevated afterload
Currently there are very few existing techniques to study cardiac metabolism in vivo Nuclear medicine techniques ie Positron Emission Tomography PET and Single Photon Emission Computer Tomography SPECT are limited in that they utilize radiolabeled tracers which cannot distinguish the tracer and its metabolic products and expose patients to ionizing radiation Hyperpolarized HP magnetic resonance spectroscopic imaging MRSI of 13C-labeled species enables large-scale determination of cellular metabolism linked to pathophysiological mechanisms of disease without the use of ionizing radiation and represents a unique and novel method to image real time in vivo cardiac metabolic substrate utilization coupled to cardiac function Currently the canonical HP compound utilized is 13C-pyruvate The short-lived non-radioactive HP 13C-pyruvate metabolites are biologically analogous to their endogenous analogues and can reveal enzymatic activity eg lactate dehydrogenase and pyruvate dehydrogenase before and after interventions that are not readily answered by PET or any other imaging method Importantly HP MRSI has the potential to reveal metabolic mechanisms associated with cardiac disease states understand the relationship of metabolism with contractile function and may be a biomarker for determining therapeutic efficacy These techniques will enable robust imaging of cardiac metabolism with quantitative measures derived from both the RV and LV Measurement of downstream products of pyruvate metabolism including lactate alanine and bicarbonate will allow for real time activity assessment of lactate dehydrogenase LDH alanine aminotransferase ALAT pyruvate dehydrogenase PDH respectively The measurement of these downstream products of metabolism namely bicarbonate and lactate will permit the assessment of the relative contribution of oxidative metabolism and glycolysis Since the imaging is performed on a clinical MRI system metabolism can be studied simultaneously with classic parameters of cardiac function
Currently there are very few existing techniques to study cardiac metabolism in vivo Nuclear medicine techniques ie Positron Emission Tomography PET and Single Photon Emission Computer Tomography SPECT are limited in that they utilize radiolabeled tracers which cannot distinguish the tracer and its metabolic products and expose patients to ionizing radiation Hyperpolarized HP magnetic resonance spectroscopic imaging MRSI of 13C-labeled species enables large-scale determination of cellular metabolism linked to pathophysiological mechanisms of disease without the use of ionizing radiation and represents a unique and novel method to image real time in vivo cardiac metabolic substrate utilization coupled to cardiac function Currently the canonical HP compound utilized is 13C-pyruvate The short-lived non-radioactive HP 13C-pyruvate metabolites are biologically analogous to their endogenous analogues and can reveal enzymatic activity eg lactate dehydrogenase and pyruvate dehydrogenase before and after interventions that are not readily answered by PET or any other imaging method Importantly HP MRSI has the potential to reveal metabolic mechanisms associated with cardiac disease states understand the relationship of metabolism with contractile function and may be a biomarker for determining therapeutic efficacy These techniques will enable robust imaging of cardiac metabolism with quantitative measures derived from both the RV and LV Measurement of downstream products of pyruvate metabolism including lactate alanine and bicarbonate will allow for real time activity assessment of lactate dehydrogenase LDH alanine aminotransferase ALAT pyruvate dehydrogenase PDH respectively The measurement of these downstream products of metabolism namely bicarbonate and lactate will permit the assessment of the relative contribution of oxidative metabolism and glycolysis Since the imaging is performed on a clinical MRI system metabolism can be studied simultaneously with classic parameters of cardiac function
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None