Hypertension, PulmonaryNCT01317134
Endothelial Function in Patients With Pulmonary Arterial Hypertension
A study testing EndoPAT measurement and Blood Test in people with Hypertension, Pulmonary and Pulmonary Arterial Hypertension, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension, Pathophysiology
- What is being tested?
- EndoPAT measurement and Blood Test
- Type of treatment
- Vaccines, Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 90 participants
- Where
- 1 siteGermany
- Study dates
- Oct 2010to Jul 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Trial locations and contacts
1 site in 1 country.
Germany1 site
Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf
Hamburg, 20246
About this study
Official title: Serological and Non-invasive Evaluation of 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.
Read the 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.
- Being tested
- EndoPAT measurement, Blood Test
- Keywords
- Pulmonary Arterial Hypertension, Prognostic factors, Signal transduction, Genetics
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EndoPAT measurementDevice
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 TestBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: Device: EndoPAT measurement; Biological: Blood Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 0, 3, 6, 9 and 12 months
Secondary outcomes (6)
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.
Measured: 0,3,6,9 and 12 months
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.
Measured: 0,3,6,9 and 12 months
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.
Measured: 0,3,6,9 and 12 months
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.
Measured: 0 months
Correlation of polymorphisms in L-arginine metabolism genes with disease severity
Measured: 0 months
Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)
Measured: 0 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Mar 2011 (estimated)
- Study startOct 2010
- Primary completionDec 2014
- Study completionJul 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 90 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer, Actelion
- Responsible party
- Sponsor
- Investigators
- Hans FE Klose, MD, Study director, Department of Respiratory Medicine, University Medical Center Hamburg-EppendorfJan K Hennigs, MD, Principal investigator, Department of Respiratory Medicine, University Medical Center Hamburg - Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01317134
- Sponsor's protocol ID
- PNEU-PV3334/2009/UKE
- Status last verified
- Aug 2022
- First submitted
- 15 Mar 2011
- Last updated
- 11 Aug 2022
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serological and Non-invasive Evaluation of Endothelial Function in Patients With Pulmonary Arterial Hypertension
- ClinicalTrials.gov ID
- NCT01317134
- Acronym / sponsor ID
- PNEU-PV3334/2009/UKE
- Keywords
- Pulmonary Arterial Hypertension, Prognostic factors, Signal transduction, Genetics
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 90 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Collaborators
- Pfizer, Actelion
- Study start
- Oct 2010 (actual)
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jul 2016 (actual)
- First posted
- 17 Mar 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Therapy-naive | Active comparator | Device: EndoPAT measurement, Biological: Blood TestThis 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 |
| Under therapy | Active comparator | Device: EndoPAT measurement, Biological: Blood TestThis 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 |
| Healthy controls | Active comparator | Device: EndoPAT measurement, Biological: Blood TestThis group consists of healthy individuals. Sex and age matching is intended. Intervention: a) Device: EndoPAT measurement and b) Biological/Vaccine: Blood |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EndoPAT measurementEndoPAT (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. | Device | Healthy controls, Therapy-naive, Under therapy |
| Blood TestIt 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. | Biological | Healthy controls, Therapy-naive, Under therapy |
Primary outcome
Differences of endothelial function regarding disease class and severity
Time frame: 0, 3, 6, 9 and 12 months
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
6 secondary outcomes
Correlation of endothelial function with changes in pulmonary hemodynamics
Time frame: 0,3,6,9 and 12 months
Correlation of endothelial function with established prognostic factors
Time frame: 0,3,6,9 and 12 months
Correlation of endothelial function with possible prognostic factors
Time frame: 0,3,6,9 and 12 months
Correlation of L-arginine metabolites with pulmonary vascular signaling
Time frame: 0 months
Correlation of polymorphisms in L-arginine metabolism genes with disease severity
Time frame: 0 months
Correlation of endothelial function with possible novel diagnostic or prognostic factors (e.g., inflammatory markers, intermediary metabolites)
Time frame: 0 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2022.
- Link to Publication of Study ResultsLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Hypertension, Pulmonary
RecruitingObservational study
Asthma and Primary Arterial Hypertension: an Inflammatory Link?
Asthma Bronchial
RecruitingPhase 1/2
HS235 Study in Overweight and Obese Participants With Combined Pre and Post-Capillary Pulmonary Hypertension Due to Heart Failure With Preserved Ejection Fraction
Pulmonary Hypertension, Heart Failure With Preserved Ejection Fraction
RecruitingPhase 2
Spironolactone for Pulmonary Arterial Hypertension
Pulmonary Arterial Hypertension
RecruitingPhase 1/2
A Study of HS235 for Treatment of Pulmonary Arterial Hypertension (PAH) in Adults
Pulmonary Arterial Hypertension
Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
Pulmonary Arterial Hypertension PAH
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hans FE Klose, MD study director
Department of Respiratory Medicine, University Medical Center Hamburg-Eppendorf
Jan K Hennigs, MD principal investigator
Department of Respiratory Medicine, University Medical Center Hamburg - Eppendorf
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing EndoPAT measurement and Blood Test in people with Hypertension, Pulmonary and Pulmonary Arterial Hypertension, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Differences of endothelial function regarding disease class and severity (time frame: 0, 3, 6, 9 and 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2022.