Endothelial Function in Patients With Pulmonary Arterial Hypertension

The recruitment status of this study is unknown because the information has not been verified recently.
Verified March 2011 by Universitätsklinikum Hamburg-Eppendorf.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
Pfizer
Actelion
Information provided by:
Universitätsklinikum Hamburg-Eppendorf
ClinicalTrials.gov Identifier:
NCT01317134
First received: March 15, 2011
Last updated: NA
Last verified: March 2011
History: No changes posted
  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:


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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 20, 2014