I27.0
Conditions
Interventions
Group 1: As part of routine examinations and laboratory tests, all patients additionally have EDTA blood and PAXgene tubes (for RNA preservation) collected. The blood samples are analyzed for the expr
Sponsors
Thoraxklinik am Universitätsklinikum Heidelberg, Sektion Pulmonale Hypertonie
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: General: - Capacity to provide informed consent - Written informed consent after appropriate explanation PAH Patients: - Diagnosis of PAH according to current guidelines (mPAP > 20 mmHg, PVR > 2 Wood Units, PAWP = 15 mmHg) - PAH patients who either fit into one of the four study arms based on their current or planned medication regimen, or who do not undergo therapy modification and serve as a control group Healthy BMPR2 Mutation Carriers: - Presence of a confirmed hereditary PAH (HPAH) diagnosis in a close relative - Documented pathogenic BMPR2 variant associated with PAH predisposition - No evidence of pulmonary hypertension based on clinical screening, including echocardiography Healthy Controls: - Age- and sex-matched to the PAH patients receiving activin ligand trap therapy - No significant cardiovascular disease - Blood sample provided after informed consent or Participants of the Lung Biobank Heidelberg, Section of Translational Research, Thorax Clinic Heidelberg, and the Biobanking & Data Management Platform of the German Center for Lung Research (DZL)
Exclusion criteria
Exclusion criteria: - Pregnancy, breastfeeding - Acute infection - Significant pulmonary disease: COPD with FEV1 < 50% predicted, interstitial pulmonary fibrosis with FVC < 60% predicted - Active malignant disease - Comorbidities potentially associated with TGF-ß signaling pathway alterations: brachydactyly, short stature, hemochromatosis (BMPR1B, BMP9); microphthalmia (BMP4); Myhre syndrome, juvenile polyposis (SMAD4); craniosynostosis, radio-ulnar synostosis (SMAD6); proximal symphalangism / multiple synostosis syndrome (Noggin); sclerosteosis (sclerostin), Loeys-Dietz syndrome (SMAD3
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in BMPR2 mRNA expression before and after escalation of background PAH therapy with an activin ligand trap | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Change in BMPR2 mRNA expression in the remaining observation groups 2. Comparison of differences in BMPR2 mRNA expression between all PAH patient groups with and without therapy modification 3. Comparison of baseline BMPR2 mRNA expression across all groups, healthy BMPR2 mutation carriers, and healthy controls 4. Secondary endpoints 1–3 applied to gene/protein expression of additional TGF-ß pathway components, such as Activin A, Activin B, Inhibin a, Inhibin ß, BMP9, and BMP10 5. Additional parameters from routine clinical examinations for characterization of the patient cohort | — |
Countries
Germany
Contacts
Public ContactChristina A. Eichstaedt
Thoraxklinik am Universitätsklinikum Heidelberg, Sektion Pulmonale Hypertonie
Outcome results
None listed