Endothelial Function in Patients With Pulmonary Arterial Hypertension

Pulmonary Arterial Hypertension Clinical Trial

Official title:

Serological and Non-invasive Evaluation of Endothelial Function in Patients With Pulmonary Arterial Hypertension

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01317134
• Other study ID #: PNEU-PV3334/2009/UKE
• Status: Completed
• Phase: N/A
• Start date: October 2010
• Est. completion date: July 2016

Study information

• Verified date: August 2022
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The objectives of the current study are to identify and evaluate new prognostic non-invasive and serological markers in patients with pulmonary hypertension. The focus will be on L-arginine metabolism and to clarify its influence on endothelial function.

Description:

The objectives of the current study are to identify and evaluate new prognostic non-invasive and serological markers in patients with pulmonary hypertension. The focus will be on L-arginine metabolism and to clarify its influence on endothelial function. The investigators also want to evaluate differences in plasma concentrations of L-arginine/NO metabolites and non-invasively assessed endothelial function based on specific PH-therapy. Furthermore, the investigators aim to transfer the results gained from the investigators study population to in-vitro systems in order to carefully characterize the involved signal transduction pathways. Thereby the investigators hope to identify potentially new therapeutic targets in PH or patient subgroups preferably benefitting from established therapeutic options.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: July 2016
• Est. primary completion date: December 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• proven PH (by right heart catheterization, PAP >25 mmHg, within last 12 months)
• age >18 years
• Dana Point classification I or IV (all subgroups)
• declaration of consent

Exclusion Criteria:

• Pulmonary Hypertension not proven by right heart catheterization
• Eisenmenger's syndrome/reaction
• PH other than Dana Point I and IV
• alcohol or drug abuse
• non-compliance due to any cause (e.g. severe psychiatric disorder)

Related Conditions & MeSH terms

• Familial Primary Pulmonary Hypertension
• Genetics
• Hypertension
• Hypertension, Pulmonary
• Pathophysiology
• Pulmonary Arterial Hypertension

Intervention

Device:
• EndoPAT measurement
EndoPAT (Itamar Medical Ltd, Ceasarea, Isreal) quantifies the endothelium-mediated changes in vascular tone, elicited by a 5-minute occlusion of the brachial artery (using a standard blood pressure cuff). When the cuff is released, the surge of blood flow causes an endothelium-dependent Flow Mediated Dilatation (FMD). The dilatation, manifested as Reactive Hyperemia, is captured by EndoPAT as an increase in the PAT Signal amplitude. A post-occlusion to pre-occlusion ratio is calculated by the EndoPAT software, providing the EndoPAT index. EndoPAT is FDA-cleared and CE-marked.

Biological:
• Blood Test
It is hypothesized that L-arginine/NO-metabolites are altered in pulmonary hypertension depending on disease severity. Moreover, polymorphisms in L-arginine/NO-metabolism modifying factors may influence disease severity. Analysis will be performed following established/published protocols after isolation from whole blood.

Locations

Country	Name	City	State
Germany	Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf	Hamburg

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Actelion, Pfizer

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Differences of endothelial function regarding disease class and severity	Quantification of L-arginine metabolites in whole blood; PAT-Ratio as non-invasively assessed endothelial function by EndoPAT2000-Device (Itamar Medical Ltd., Caesarea, Israel); 0 months = Time of Inclusion	0, 3, 6, 9 and 12 months
Secondary	Correlation of endothelial function with changes in pulmonary hemodynamics	L-arginine metabolite concentrations and PAT-Ratio correlated with PAPm, RAP, PVR (assessed by right heart catheterization within 12 months prior to inclusion) and echocardiographical parameters RVSP, TAPSE and TEI.	0,3,6,9 and 12 months
Secondary	Correlation of endothelial function with established prognostic factors	L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of proBNP as well as capillary pCO2, 6-minute walk distance and NYHA/WHO functional class.	0,3,6,9 and 12 months
Secondary	Correlation of endothelial function with possible prognostic factors	L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of various enzymes as well as lung function.	0,3,6,9 and 12 months
Secondary	Correlation of L-arginine metabolites with pulmonary vascular signaling	In vitro evaluation of human pulmonary vasculature cells signaling and proliferation by altered L-arginine metabolite levels.	0 months
Secondary	Correlation of polymorphisms in L-arginine metabolism genes with disease severity		0 months
Secondary	Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)		0 months

External Links

•   Link to Publication of Study Results