Endothelial Function in Patients With Pulmonary Arterial Hypertension - Full Text View

Purpose

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.

Condition	Intervention
Hypertension, Pulmonary Pulmonary Arterial Hypertension Functional Disorder Genetics	Device: EndoPAT measurement Biological: Blood Test

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Diagnostic
Official Title:	Serological and Non-invasive Evaluation of Endothelial Function in Patients With Pulmonary Arterial Hypertension

Resource links provided by NLM:

Genetics Home Reference related topics: pulmonary arterial hypertension

MedlinePlus related topics: High Blood Pressure Pulmonary Hypertension

U.S. FDA Resources

Further study details as provided by Universitätsklinikum Hamburg-Eppendorf:

Primary Outcome Measures:

Differences of endothelial function regarding disease class and severity [ Time Frame: 0, 3, 6, 9 and 12 months ] [ Designated as safety issue: No ]
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:

Correlation of endothelial function with changes in pulmonary hemodynamics [ Time Frame: 0,3,6,9 and 12 months ] [ Designated as safety issue: No ]
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 endothelial function with established prognostic factors [ Time Frame: 0,3,6,9 and 12 months ] [ Designated as safety issue: No ]
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 [ Time Frame: 0,3,6,9 and 12 months ] [ Designated as safety issue: No ]
L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of various enzymes as well as lung function.
Correlation of L-arginine metabolites with pulmonary vascular signaling [ Time Frame: 0 months ] [ Designated as safety issue: No ]
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 [ Time Frame: 0 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	90
Study Start Date:	July 2010
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Therapy-naive 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.	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.
Active Comparator: Under therapy 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.	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.
Active Comparator: Healthy controls This group consists of healthy individuals. Sex and age matching is intended.	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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01317134

Contacts

Contact: Hans FE Klose, MD	+4940 7410 ext 57395	klose@uke.uni-hamburg.de
Contact: Jan K Hennigs, MD	+4940 7410 ext 57395	j.hennigs@uke.uni-hamburg.de

Locations

Germany
Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf	Recruiting
Hamburg, Germany, 20246
Contact: Hans FE Klose, MD +4940 7410 ext 57395 klose@uke.uni-hamburg.de
Contact: Jan K Hennigs, MD +4940 7410 ext 57395 j.hennigs@uke.uni-hamburg.de
Principal Investigator: Nicole Burhenne, PhD
Sub-Investigator: Hans Jörg Baumann, MD
Sub-Investigator: Jan Heyckendorf, MD
Sub-Investigator: Stephan Baldus, MD, PhD
Sub-Investigator: Rainer H Böger, MD, PhD

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Pfizer

Actelion

Investigators

Study Director:	Hans FE Klose, MD	Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf
Principal Investigator:	Jan K Hennigs, MD	Department of Respiratory Medicine, University Medical Center Hamburg - Eppendorf

More Information

No publications provided

Responsible Party:	Dr. Hans F.E. Klose, MD, Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:	NCT01317134 History of Changes
Other Study ID Numbers:	PNEU-PV3334/2009/UKE
Study First Received:	March 15, 2011
Last Updated:	March 15, 2011
Health Authority:	Germany: Local Ethics Committee, Ärztekammer Hamburg

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:

Pulmonary Arterial Hypertension
Prognostic factors
Signal transduction
Genetics

Additional relevant MeSH terms:

Hypertension, Pulmonary
Hypertension
Lung Diseases

Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on May 19, 2013