Ignite Creation Date:
2024-05-06 @ 4:11 PM
Last Modification Date:
2024-10-26 @ 2:05 PM
Study NCT ID:
NCT04908397
Status:
COMPLETED
Last Update Posted:
2024-02-14
First Post:
2021-05-17
Brief Title:
Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension
Sponsor:
Vanderbilt University Medical Center
Organization:
Vanderbilt University Medical Center
Study Overview
Official Title:
Carnitine Consumption and Augmentation in Pulmonary Arterial Hypertension
Status:
COMPLETED
Status Verified Date:
2024-02
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:
In preparation for a future mechanistic study investigators now propose to test the specific hypothesis that carnitine consumption is not reduced in PAH that plasma carnitine levels are stable over time in PAH and that carnitine supplementation in PAH can increase plasma carnitine and thereby delivery of carnitine to the RV and possibly improve RV function Investigators propose three aims in humans to test this mechanistic hypothesis 1 Measure the oral consumption of carnitine in human PAH This aim will use food diaries and carnitine supplement use questionnaires in PAH patients to test the hypothesis that carnitine supplementation is uncommon in PAH and food consumption is adequate Aim 2 Measure the stability over time in plasma carnitine levels in PAH patients This aim will test the hypothesis that plasma carnitine is not affected by disease severity and is stable over time in PAH patients Investigators will measure plasma carnitine concentration and markers of fatty acid oxidation at Visit 1 and Visit 2 3 Perform a mechanistic pilot study using carnitine supplementation to enhance circulating carnitine in PAH This small pilot study will test the hypothesis that carnitine supplementation increases plasma carnitine primary endpoint and will test for physiologic effects using six minute walk testing echocardiography and plasma markers of lipid metabolism
Detailed Description:
Right ventricular RV failure is the most common cause of death in pulmonary arterial hypertension PAH No RV-specific therapies are available in part because the underlying mechanisms of RV failure are poorly understood A growing body of evidence suggests that metabolic abnormalities may underlie RV dysfunction in PAH Interventions against metabolic dysfunction in PAH may protect against RV failure Investigators in the PH research group have identified abnormalities in fatty acid FA metabolism in PAH that overlap considerably with disorders of carnitine deficiency Carnitine links to an acyl group which is required to transport FAs across the mitochondrial membrane to undergo beta-oxidation the predominate source of ATP production in the human heart Inborn errors of carnitine metabolism and acquired carnitine deficiency are associated with cardiomyopathy Acquired deficiency primarily occurs via binding of carnitine to excess circulating fatty acids or renal wasting Carnitine deficiency and PAH are both associated with insulin resistance myocardial lipotoxicity and mitochondrial oxidative stress Carnitine supplementation in humans and animal models of cardiometabolic dysfunction reverses these abnormalities but has not been studied in PAH In published work investigators found that in RV samples from humans with PAH there is a marked up to 300-fold reduction in acylcarnitines along with increased long-chain fatty acids Investigators also a found a two-fold increase in circulating fatty acids FAs in humans with PAH indicating increased delivery to the myocardium As a consequence of unchecked fatty acid accumulation investigators observed 7-fold higher RV lipid content and markers of lipotoxicity These observations suggest there is inadequate carnitine substrate to bind fatty acids and facilitate their transport across the mitochondrial membrane in the human PAH RV
The investigators overarching hypothesis is that in human PAH RV function can be improved by augmenting carnitine substrate availability to improve outcomes In preparation for a future mechanistic study Vanderbilt PAH research investigators now propose to test the specific hypothesis that carnitine consumption is not reduced in PAH that plasma carnitine levels are stable over time in PAH and that carnitine supplementation in PAH can increase plasma carnitine and thereby delivery of carnitine to the RV and possibly improve RV function Investigators propose three aims in humans to test this mechanistic hypothesis 1 Measure the oral consumption of carnitine in human PAH This aim will use food diaries and carnitine supplement use questionnaires in PAH patients to test the hypothesis that carnitine supplementation is uncommon in PAH and food consumption is adequate Aim 2 Measure the stability over time in plasma carnitine levels in PAH patients This aim will test the hypothesis that plasma carnitine is not affected by disease severity and is stable over time in PAH patients The study will measure plasma carnitine concentration and markers of fatty acid oxidation at Visit 1 and Visit 2 3 Perform a mechanistic pilot study using carnitine supplementation to enhance circulating carnitine in PAH This small pilot study will test the hypothesis that carnitine supplementation increases plasma carnitine primary endpoint and will test for physiologic effects using six minute walk testing echocardiography and plasma markers of lipid metabolism
The investigators overarching hypothesis is that in human PAH RV function can be improved by augmenting carnitine substrate availability to improve outcomes In preparation for a future mechanistic study Vanderbilt PAH research investigators now propose to test the specific hypothesis that carnitine consumption is not reduced in PAH that plasma carnitine levels are stable over time in PAH and that carnitine supplementation in PAH can increase plasma carnitine and thereby delivery of carnitine to the RV and possibly improve RV function Investigators propose three aims in humans to test this mechanistic hypothesis 1 Measure the oral consumption of carnitine in human PAH This aim will use food diaries and carnitine supplement use questionnaires in PAH patients to test the hypothesis that carnitine supplementation is uncommon in PAH and food consumption is adequate Aim 2 Measure the stability over time in plasma carnitine levels in PAH patients This aim will test the hypothesis that plasma carnitine is not affected by disease severity and is stable over time in PAH patients The study will measure plasma carnitine concentration and markers of fatty acid oxidation at Visit 1 and Visit 2 3 Perform a mechanistic pilot study using carnitine supplementation to enhance circulating carnitine in PAH This small pilot study will test the hypothesis that carnitine supplementation increases plasma carnitine primary endpoint and will test for physiologic effects using six minute walk testing echocardiography and plasma markers of lipid metabolism
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