Active clinical trials for "Familial Primary Pulmonary Hypertension"

Previous studies suggest that combinations of existing therapies may be effective for pulmonary arterial hypertension (PAH). However, all of these studies are sequential combination therapy, for example, by adding sildenafil to previously prescribed bosentan. This kind of therapy model is not enough for PAH patients, especially those with New York Heart Association (NYHA) class Ⅲ and Ⅳ. In this randomized, multicenter study, the investigators evaluate the safety and efficacy of combining inhaled iloprost, a prostacyclin analog, with the endothelin receptor antagonist bosentan in treatment naive patients with PAH by comparing with bosentan monotherapy. Efficacy endpoints include change from baseline in 6-min-walk distance (6-MWD), modified (NYHA) functional class, hemodynamic parameters, and time to clinical worsening.

Patients with idiopathic pulmonary arterial hypertension (IPAH) and iron deficiency were previously shown to have a decreased six-minute walking distance. Therefore the investigators hypothesized that intravenous iron administration would improve exercise capacity in iron deficient IPAH patients. 30 patients will be recruited for iron infusions. At baseline and after 12 weeks (endpoint)exercise test will be performed.

To determine the prevalence of myelofibrosis in patients with primary pulmonary hypertension, and to discover if the fibrosis in these patients is primary (AMM) or secondary.

Pulmonary arterial hypertension is a disease characterised by pathological changes in the pulmonary arteries leading to a progressive increase in pulmonary vascular resistance and pulmonary artery pressure. Right ventricular failure is the main cause of death in patients with pulmonary arterial hypertension, and the ability of the right ventricle to adapt to the progressive increase in pulmonary vascular resistance associated with changes to the pulmonary vasculature in pulmonary arterial hypertension is the main determinant of a patient's functional capacity and survival. Right ventricular dyssynchrony was present in a substantial proportion of patients with pulmonary arterial hypertension and this dyssynchrony adversely affected right ventricular function.

Patients suffering from pulmonary arterial hypertension (PAH) frequently remain symptomatic despite medical therapy. Symptoms include breathlessness, poor exercise capacity and reduced quality of life. In many other serious heart or lung diseases it has been shown that physical rehabilitation improves patient's fitness and quality of life. In PAH there are no clear guidelines and in general physical activity has traditionally been discouraged, although evidence for this advice is lacking. Interesting research project in Germany showed significant benefit for in-patient rehabilitation in PAH patients. In this study we will perform a controlled clinical study of out-patient rehabilitation of patients with PAH. We hypothesize that physical training of patients will result in increased exercise capacity and improved quality of life.

Pulmonary artery hypertension (PAH) is a rare, severe disease, characterized by a progressive increase in pulmonary vascular resistance ultimately leading to right ventricular (RV) failure and premature death. PAH may be idiopathic (IPAH) or may be also related to various conditions like portal hypertension, HIV infection, left to right shunt, connective tissue diseases such as scleroderma (PAHSSc). Symptoms include dyspnea and fatigue resulting in restricted exercise capacity and poor quality of life. The therapies currently approved have been shown to improve survival. Indeed, recent studies described a three year survival higher than 80%. This improved survival is associated with major challenges for clinicians as most patients remain with limited exercise capacity and poor quality of life. A clear understanding of exercise physiopathology is thus mandatory to specifically address mechanisms responsible for this exercise limitation and eventually improve patients' management. In order to better characterize the exercise physiopathology in PAH, the general objective of this research is to systematically examine blood flow distribution and limb muscles microcirculation at rest and during submaximal exercise in PAH.

The purpose of this study is to determine the clinical, functional and hemodynamic response after six months of sildenafil 50 mg TID 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.

The overall objective of this study is to fulfill the Pilot study (miRNA and Myokines Acutely-expressed During Exercise) goal to Investigate the excretion of skeletal muscle-derived miRNA and myokines in patients with pulmonary arterial hypertension during acute exercise that are biologically active and modulate skeletal muscle function during exercise. Pulmonary arterial hypertension (PAH), is characterized by the proliferation of endothelial and smooth muscle cells within the precapillary pulmonary vasculature, if untreated results in increased pulmonary vascular resistance and death. The hallmark perivascular infiltrates in PAH contain inflammatory macrophages and lymphocytes resulting in endothelial dysfunction and involves the dysregulation of distinct inflammatory mechanisms. Idiopathic PAH (iPAH) and scleroderma-associated PAH (SSc-PAH), are related by similar clinical and pathophysiologic features. Patients with PAH experience a central cardiovascular limitation to exercise. Despite effective treatment with pulmonary vasodilators, many resting PAH (rPAH) patients continue to experience exercise intolerance. PAH is increasingly acknowledged as a systemic disease, beyond abnormalities of the pulmonary vasculature. Although other contributions to exercise intolerance in PAH exist, skeletal muscle dysfunction significantly impacts exercise tolerance. The molecular mechanisms behind skeletal muscle dysfunction in PAH remain unclear. Provocative testing with invasive cardiopulmonary exercise testing challenges the cardio-pulmonary-vascular and skeletal muscle systems and elicits a cascade of physiologic events not measurable at rest. Myokines are circulating mediators released from skeletal muscle in an endocrine-like fashion in disease and health influencing many factors but not limited to systemic inflammation, immunity and endothelial function. Myokines have not been well described in PAH. Preliminary data indicate that myokines play important, yet still undescribed, roles in this disease. MicroRNAs (miRNAs) are small non-coding RNA molecules, which negatively regulate gene expression via repressing translation and degrading messenger RNAs through sequence-specific binding. There is a growing literature regarding the biological activity of extracellular miRNAs in PAH and in aerobic exercise. miR-126 has been implicated in skeletal muscle dysfunction in PAH, while miR-133 is skeletal muscle-specific but unlike miR-126 it is not yet implicated in skeletal muscle dysfunction in PAH.

Treatment of PAH includes exercise limitation, non specific agents (anticoagulants, diuretics and supplemental oxygen), pulmonary specific vasodilators and antiproliferative agents. Recent data obtained by our group, within rat PAH models, showed that the antihyperglycemic drug metformin, used in France since 1959 in diabetic type II patients, significantly acts at the pulmonary arteries level. According to these results, and knowing that metformin is a widely used drug, with a favorable safety profile, the investigators decided to set up a pilot study, in order to evaluate the activity of metformin in PAH treatment. In parallel, the investigators will focus on metformin mechanism of action.