Clinical Trial: Physiopathology of Pulmonary Arterial Hypertension: Mechanistic Studies

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Physiopathology of Pulmonary Arterial Hypertension: Mechanistic Studies

Brief Summary: The current aims to combine analysis of different inflammatory biomarkers and BMPR2 mutations, which are currently analyzed in each patient diagnosed with idiopathic or familial PAH, to establish an earlier diagnosis and consequently better orientate the therapeutic strategy in PAH.

Detailed Summary:

BACKGROUND

Pulmonary hypertension is a severe disorder defined by an elevated mean pulmonary arterial pressure (mPAP) as >25 mmHg at rest. A classification of the different types of pulmonary hypertension has been established according to shared pathologic and clinical features as well as similar therapeutic options and recently updated. Five major categories have been defined including 1) pulmonary arterial hypertension (PAH), 2) PH owing to left heart diseases, 3) PH owing to lung diseases and/or hypoxia, 4) chronic thromboembolic PH (CTEPH) and 5) PH with unclear multifactorial mechanisms.

PAH commonly defined by an elevated PAP (>25 mmHg at rest) and a normal pulmonary arterial wedge pressure (<15 mmHg), is characterized by a pre-capillary arteriopathy with the presence of vascular remodeling and formation of plexiform lesions, an increased pulmonary vascular resistance (PVR), which may result in right heart failure. PAH may be idiopathic (IPAH), heritable (HPAH) or associated with drug/toxin exposure or other medical conditions including connective tissue diseases, congenital heart diseases, human immunodeficiency virus or portal hypertension. Familial cases were already reported in the early fifties and, in 2000, bone morphogenic protein receptor type 2 gene (BMPR2) was identified as the gene responsible for more than 70% of HPAH and about 20% of IPAH. BMPR2 belongs to a superfamily of growth factor receptors, including bone morphogenic protein (BMPs) and transforming growth factor beta (TGF-β) and consequently controls cellular functions such as proliferation, migration, differentiation or apoptosis. BMPR2 mutations may favor activation of p38MAPK-dependent pro-proliferative pathways, which is also ; a key player in cytokine-induced inflammatory signaling pathways. Although BMPR2 mutation carriers deve
Sponsor: Universitaire Ziekenhuizen Leuven

Current Primary Outcome: Circulating Inflammatory Biomarkers: CRP, total cholesterol, HDL-cholesterol, triglycerides, albumin, Lp-PLA2 activity, Thrombin Activatable Fibrinolysis Inhibitor (TAFI), vitamin D [ Time Frame: Changes from baseline in circulating inflammatory biomarkers will be evaluated at 6 months, 12 months and 24 months whenever a right heart catheterization will be performed after starting a treatment ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

Original Secondary Outcome:

Information By: Universitaire Ziekenhuizen Leuven

Dates:
Date Received: April 23, 2015
Date Started: January 2015
Date Completion: December 2020
Last Updated: November 8, 2016
Last Verified: November 2016