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Completed

NCT Number: NCT01317134

Endothelial Function in Patients With Pulmonary Arterial Hypertension

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.

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Key information

Conditions

Hypertension, Pulmonary Cardiovascular Diseases Genetics Hypertension Lung Diseases Pathophysiology Pulmonary Arterial Hypertension Respiratory Tract Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

EndoPAT measurement

Device

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.

blood test

Biological

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.

Primary outcomes

  1. Differences of endothelial function regarding disease class and severity

    Time frame: 0, 3, 6, 9 and 12 months

    • 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

Secondary outcomes

  1. Correlation of endothelial function with changes in pulmonary hemodynamics

    Time frame: 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.

  2. Correlation of endothelial function with established prognostic factors

    Time frame: 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.

  3. Correlation of endothelial function with possible prognostic factors

    Time frame: 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.

  4. Correlation of L-arginine metabolites with pulmonary vascular signaling

    Time frame: 0 months

    In vitro evaluation of human pulmonary vasculature cells signaling and proliferation by altered L-arginine metabolite levels.

  5. Correlation of polymorphisms in L-arginine metabolism genes with disease severity

    Time frame: 0 months

  6. Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)

    Time frame: 0 months

Sponsors and collaborators

Lead sponsor

Universitätsklinikum Hamburg-Eppendorf

Other

Collaborators

  • Actelion
  • Pfizer

Registry information

Official study title

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

Important dates

Study start
2010
Primary completion
2014
Study completion
2016
First posted
Mar 17, 2011
Registry last updated
Aug 11, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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