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Endothelial Function in Patients With Pulmonary Arterial Hypertension

Primary Purpose

Hypertension, Pulmonary, Pulmonary Arterial Hypertension, Pathophysiology

Status
Completed
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
EndoPAT measurement
Blood Test
Sponsored by
Universitätsklinikum Hamburg-Eppendorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Hypertension, Pulmonary focused on measuring Pulmonary Arterial Hypertension, Prognostic factors, Signal transduction, Genetics

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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)

Sites / Locations

  • Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Active Comparator

Active Comparator

Arm Label

Therapy-naive

Under therapy

Healthy controls

Arm Description

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

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

This group consists of healthy individuals. Sex and age matching is intended. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood

Outcomes

Primary Outcome Measures

Differences of endothelial function regarding disease class and severity
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 Outcome Measures

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

Full Information

First Posted
March 15, 2011
Last Updated
August 8, 2022
Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Pfizer, Actelion
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1. Study Identification

Unique Protocol Identification Number
NCT01317134
Brief Title
Endothelial Function in Patients With Pulmonary Arterial Hypertension
Official Title
Serological and Non-invasive Evaluation of Endothelial Function in Patients With Pulmonary Arterial Hypertension
Study Type
Interventional

2. Study Status

Record Verification Date
August 2022
Overall Recruitment Status
Completed
Study Start Date
October 2010 (Actual)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
July 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Universitätsklinikum Hamburg-Eppendorf
Collaborators
Pfizer, Actelion

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension, Pulmonary, Pulmonary Arterial Hypertension, Pathophysiology, Genetics
Keywords
Pulmonary Arterial Hypertension, Prognostic factors, Signal transduction, Genetics

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Therapy-naive
Arm Type
Active Comparator
Arm Description
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
Arm Title
Under therapy
Arm Type
Active Comparator
Arm Description
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
Arm Title
Healthy controls
Arm Type
Active Comparator
Arm Description
This group consists of healthy individuals. Sex and age matching is intended. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood
Intervention Type
Device
Intervention Name(s)
EndoPAT measurement
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Blood Test
Intervention Description
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 Outcome Measure Information:
Title
Differences of endothelial function regarding disease class and severity
Description
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
Time Frame
0, 3, 6, 9 and 12 months
Secondary Outcome Measure Information:
Title
Correlation of endothelial function with changes in pulmonary hemodynamics
Description
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.
Time Frame
0,3,6,9 and 12 months
Title
Correlation of endothelial function with established prognostic factors
Description
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.
Time Frame
0,3,6,9 and 12 months
Title
Correlation of endothelial function with possible prognostic factors
Description
L-arginine metabolite concentrations and PAT-Ratio correlated with plasma concentration of various enzymes as well as lung function.
Time Frame
0,3,6,9 and 12 months
Title
Correlation of L-arginine metabolites with pulmonary vascular signaling
Description
In vitro evaluation of human pulmonary vasculature cells signaling and proliferation by altered L-arginine metabolite levels.
Time Frame
0 months
Title
Correlation of polymorphisms in L-arginine metabolism genes with disease severity
Time Frame
0 months
Title
Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)
Time Frame
0 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Hans FE Klose, MD
Organizational Affiliation
Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Jan K Hennigs, MD
Organizational Affiliation
Department of Respiratory Medicine, University Medical Center Hamburg - Eppendorf
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf
City
Hamburg
ZIP/Postal Code
20246
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://ediss.sub.uni-hamburg.de/handle/ediss/7300
Description
Link to Publication of Study Results

Learn more about this trial

Endothelial Function in Patients With Pulmonary Arterial Hypertension

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