Endothelial Function in Patients With Pulmonary Arterial Hypertension

NCT01317134 | Completed

• 1 other identifier: PNEU-PV3334/2009/UKE
• Study Type: interventional
• Target: 90
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Pathophysiology; Genetics

Keywords

Pulmonary Arterial Hypertension; Prognostic factors; Signal transduction; Genetics

Outcome Measures

Primary Outcomes (1)

• Differences of endothelial function regarding disease class and severity

  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

  0, 3, 6, 9 and 12 months

Secondary Outcomes (6)

• Correlation of endothelial function with changes in pulmonary hemodynamics

  0,3,6,9 and 12 months

• Correlation of endothelial function with established prognostic factors

  0,3,6,9 and 12 months

• Correlation of endothelial function with possible prognostic factors

  0,3,6,9 and 12 months

• Correlation of L-arginine metabolites with pulmonary vascular signaling

  0 months

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

  0 months

Study Arms (3)

Therapy-naive

ACTIVE COMPARATOR

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

Device: EndoPAT measurement; Biological: Blood Test

Under therapy

ACTIVE COMPARATOR

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

Device: EndoPAT measurement; Biological: Blood Test

Healthy controls

ACTIVE COMPARATOR

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

Device: EndoPAT measurement; Biological: Blood Test

Interventions

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.

Healthy controls; Therapy-naive; Under therapy

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.

Healthy controls; Therapy-naive; Under therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Universitätsklinikum Hamburg-Eppendorf: lead
• Pfizer: collaborator
• Actelion: collaborator

Study Sites (1)

Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Related Links

• Link to Publication of Study Results

MeSH Terms

Conditions

Hypertension, Pulmonary; Pulmonary Arterial Hypertension

Interventions

Hematologic Tests

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Hans FE Klose, MD

  Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf

  STUDY DIRECTOR

• Jan K Hennigs, MD

  Department of Respiratory Medicine, University Medical Center Hamburg - Eppendorf

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2011
• First Posted: March 17, 2011
• Study Start: October 1, 2010
• Primary Completion: December 1, 2014
• Study Completion: July 1, 2016
• Last Updated: August 11, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)