Endothelial Function in Patients With Pulmonary Arterial Hypertension

Not Applicable

Completed

• Conditions: Pulmonary Arterial Hypertension; Genetics; Hypertension, Pulmonary; Pathophysiology

• Registration Number: NCT01317134
• Lead Sponsor: Universitätsklinikum Hamburg-Eppendorf

Brief 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.

Detailed 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.

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2011-03-15
• Study First Submitted QC: 2011-03-15
• Study First Posted: 2011-03-17
• Primary Completion: 2014-12
• Study Completion: 2016-07
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-08
• Last Update Posted: 2022-08-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Differences of endothelial function regarding disease class and severity	0, 3, 6, 9 and 12 months	1. Quantification of L-arginine metabolites in whole blood; 2. PAT-Ratio as non-invasively assessed endothelial function by EndoPAT2000-Device (Itamar Medical Ltd., Caesarea, Israel); 0 months = Time of Inclusion

Secondary Outcome Measures

Name	Time	Method
Correlation of endothelial function with changes in pulmonary hemodynamics	0,3,6,9 and 12 months	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.
Correlation of L-arginine metabolites with pulmonary vascular signaling	0 months	In vitro evaluation of human pulmonary vasculature cells signaling and proliferation by altered L-arginine metabolite levels.
Correlation of polymorphisms in L-arginine metabolism genes with disease severity	0 months
Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)	0 months
Correlation of endothelial function with established prognostic factors	0,3,6,9 and 12 months	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.
Correlation of endothelial function with possible prognostic factors	0,3,6,9 and 12 months	L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of various enzymes as well as lung function.

Trial Locations

Locations (1)

Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf; 🇩🇪 Hamburg, Germany