Endothelial Function in Patients With Pulmonary Arterial Hypertension
- Conditions
- Pulmonary Arterial HypertensionGeneticsHypertension, PulmonaryPathophysiology
- Interventions
- Device: EndoPAT measurementBiological: Blood Test
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 90
- 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
- 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
- Arm && Interventions
Group Intervention Description Therapy-naive EndoPAT measurement This group consists of patients with a newly diagnosed PH (Class I or IV). First blood sampling takes place before initiation of PH therapy (0 months), the following measurements will be performed after 3, 6, 9 and 12 months under specific therapy. Initiation of standard therapy is performed directly after baseline visit / study inclusion. No special study medication will be used. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Test Under therapy Blood Test This group consists of patients under ERA monotherapy at timepoint of inclusion. Observation period is one year to detect intraindividual changes in endothelial dysfunction measured by L-arginine/NO-metabolites after 0, 3, 6, 9 and 12 months under investigation. Specific PAH therapy has been started prior to the study for medical reasons and will be continued throughout. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Healthy controls EndoPAT measurement This group consists of healthy individuals. Sex and age matching is intended. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Under therapy EndoPAT measurement This group consists of patients under ERA monotherapy at timepoint of inclusion. Observation period is one year to detect intraindividual changes in endothelial dysfunction measured by L-arginine/NO-metabolites after 0, 3, 6, 9 and 12 months under investigation. Specific PAH therapy has been started prior to the study for medical reasons and will be continued throughout. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Healthy controls Blood Test This group consists of healthy individuals. Sex and age matching is intended. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Therapy-naive Blood Test This group consists of patients with a newly diagnosed PH (Class I or IV). First blood sampling takes place before initiation of PH therapy (0 months), the following measurements will be performed after 3, 6, 9 and 12 months under specific therapy. Initiation of standard therapy is performed directly after baseline visit / study inclusion. No special study medication will be used. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood Test
- 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