Active clinical trials for "Familial Primary Pulmonary Hypertension"

To assess the correlation between pulmonary IV-OCT and pulmonary IV-US measurements and standard PAH clinical measures of disease progression and the relative sensitivity of the techniques to change.

This is a multi-centre, multinational, open-label, single-dose acute hemodynamic study followed by randomized, double-blind, parallel-group, placebo controlled study. Eligible subjects will undergo an open-label, single-dose acute hemodynamic study with ACT-293987(NS-304) and 21 weeks of double-blind treatment during which subjects will receive either ACT-293987 (NS-304) or placebo b.i.d. Subjects who have completed the double-blind study can enter the open extension study (separate protocol) and receive administration of ACT-293987 (NS-304) if the subject wishes and the Investigator considers it appropriate.

The EAGLE study is a Phase 3, open-label, multi-center, two-part, single-arm study of GeNOsyl(R) delivery system(s) to evaluate if inhaled nitric oxide-induced vasodilation predicts successful wean from parenteral prostacyclin (PGI) in subjects with World Health Organization (WHO) Group 1 pulmonary arterial hypertension (PAH) undergoing a medically necessary right heart catheterization (RHC). All subjects enrolled in the study will undergo an attempt to wean from parenteral PGI per standard of care.

Pulmonary Arterial Hypertension has gone from a disease that causes rapid death to a more chronic condition. Yet, improved survival is associated with major challenges for clinicians as most patients remain with poor quality of life and limited exercise capacity. The effects of exercise training on exercise capacity have been largely evaluated and showed an improvement in 6-minutes walking distance (6MWD), peak V'O2. It is also known that exercise program improves quality of life. Maximal volitional and nonvolitional strength of the quadriceps are reduced in patients with Pulmonary Arterial Hypertension and correlated to exercise capacity. Moreover, on the cellular level, alterations are observed in both the respiratory as well as the peripheral muscles. Muscle fiber size has been reported to be decreased in some studies or conversely unaltered in human and animal models. Reduction in type I fibers and a more anaerobic energy metabolism has also been reported, but not in all studies. Likewise, a loss in capillary density in quadriceps of patients with Pulmonary Arterial Hypertension and rats has been reported, but could not be confirmed in other studies. While the impact of exercise training on clinical outcomes such as exercise capacity or quality of life is well known, this data highlight the fact that the underlying causes of peripheral muscle weakness as well as the mechanisms underlying the clinical improvements observed with exercise programs are not completely understood. Improvement of muscle cell metabolism in part via the enhancement of oxidative cellular metabolism and decrease in intracellular lipid accumulation may play a role in improving muscle function and exercise capacity. In this study, we intend to evaluate the impact of a 12 weeks home-based rehabilitation program on peripheral muscle function and metabolism, focusing on lipid infiltration, oxidative metabolism and epigenetic factors that can be involved in metabolic syndrome, in patients with Pulmonary Arterial Hypertension.

The purpose of this study is to determine if there is a greater effect to patients with advanced pulmonary arterial hypertension (PAH) by using a combination of two drugs, Treprostinil and Riociquat versus Treprostinil alone

Under placebo control, the investigators intend to evaluate the effectiveness and safety of anti-inflammatory therapy and/or targeted drug therapy for early treatment of patients with pulmonary arterial hypertension.

The purpose of this study is to determine whether pulmonary arterial hypertension can worsen or even cause sleep apnea. It is hypothesized that if pulmonary arterial hypertension does indeed worsen or cause sleep apnea, then the treatment should first focus on the underlying pulmonary arterial hypertension instead of the sleep apnea. To determine if a person has sleep apnea, they will undergo one overnight polysomnogram (sleep study). If it is found that they have mild to moderate sleep apnea, then the subject will be invited to continue in the study and their pulmonary arterial hypertension will be treated by their managing primary physician. After the subject has had treatment for their pulmonary arterial hypertension, the study center will have them return for a follow up sleep study to learn the effects of pulmonary arterial hypertension treatment management on their sleep apnea, 12-24 weeks after the first sleep study.

SUMMARY Rationale: Pulmonary arterial hypertension (PAH) can be a rapidly progressive disorder and is associated with a high mortality rate, despite medical intervention. With the availability of effective therapy, early disease detection is an important strategic objective to improve treatment outcomes. Resting echocardiography is currently the recommended screening modality for high-risk population groups. However, it is clear that abnormalities in resting hemodynamics (and symptoms) are late sequelae of the pathobiological processes that begin in the distal pulmonary arteries. Exercise stress may unmask early pulmonary vascular dysfunction, however the definition, clinical significance, and natural history of 'exercise PAH' remain undefined. However, based on clinical experience and literature the prevalence is estimated at ~ 20%.Treatment with endothelin receptor blockers has shown a beneficial influence on the clinical performance in patients with exercise induced PAH due to systemic sclerosis and primary pulmonary hypertension. Whether endothelin receptor blockers decrease pulmonary pressures and improve clinical outcome in patients with exercise induced pulmonary arterial hypertension due to congenital heart disease is unknown. Objective: Identify congenital heart disease patients with exercise-induced pulmonary arterial hypertension. Analyze changes in pulmonary arterial pressures at peak exercise in patients with exercise induced pulmonary arterial hypertension before and after treatment with bosentan, compared to placebo. Study design: Randomized placebo controlled trial with a study period of 26 weeks. Study population: Adult congenital heart disease patients with exercise induced pulmonary arterial hypertension (n=40) from the Academic Medical Centre, Amsterdam. Intervention: After randomization one group (n=20) receives a 125 mg tablet of Bosentan twice daily for 6 months. The other group (n=20) receives placebo for 6 months. Main study parameters/endpoints: To determine wether bosentan (endothelin receptor inhibitor) decreases mean pulmonary arterial pressure at peak exercise in adult congenital heart disease patients with exercise induced pulmonary arterial hypertension. Furthermore the change in cardiopulmonary exercise capacity and right ventricular function will be investigated. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All investigations, blood analysis excepted, are non-invasive and free of risk. The burden for the patients mainly consists of the time that is consumed by the investigations, namely: history taking + physical examination (15 min); Quality-of-Life- score (15 min); laboratory tests (electrolytes, creatinine, urea, albumin and neurohormones, troponin T); 12 lead electrocardiogram (10 min); exercise echocardiography (30 min); cardiovascular exercise testing (30 min). The trial medication has a potential risk of liver damage, which will be monitored regularly by laboratory testing of liver transaminases.

The main question of this study is: 'Is selective beta-blocker treatment safe and effective in reducing sympathetic overdrive, thereby improving RV function and remodeling in patients with iPAH?'. In addition to the determination of RVEF, the investigators will explore how beta-blocker therapy affects sympathetic overdrive, remodeling of the RV, single beat elastance, exercise capacity and mechanical efficiency. 30 iPAH patients will be randomized to either Bisoprolol- or placebo-treatment in a double-blinded fashion. A cross-over trial design will be used to increase the power of the study and to assess long-term effects of Bisoprolol-treatment and -withdrawal. The medication will be given in an escalating dose regimen (as described in the 'farmacotherapeutisch kompas', www.fk.cvz.nl) and treatment will be monitored along the guidelines of the American Heart Association.

Pulmonary arterial hypertension (PAH) is a disease that causes raised blood pressure in blood vessels that pick up oxygen from the lungs. It has a life expectancy similar to some cancers. There is treatment available but there is no cure. We now know that PAH is associated with weakness in the muscles in the legs, which contributes to the symptoms patients' experience. Researchers believe that certain proteins found in high levels in the blood of patients with other chronic diseases can affect muscle function and growth. One of these proteins is called growth differentiating factor (GDF) 8, high levels of which are associated with muscle weakness in chronic obstructive pulmonary disease(COPD) and heart failure (HF). Interestingly there are drugs available which block the actions of GDF-8 on muscle cells which has been shown in animals to result in increased muscle size. A related protein called GDF-15 is found in elevated levels in patients PAH, and is linked to prognosis. Our preliminary data suggests that GDF-15 can also directly influence muscle size in a number of situations. We aim to investigate the role of GDF-15 and related molecules in the development of muscle weakness in patients with PAH. We will do this by measuring certain markers of muscle weakness and taking blood and muscle samples in patients and controls. We will then compare the levels of GDF-15 in these tissues in those with and without muscle wasting. We hope this work will lead to a greater understanding of the role of GDF-15 in the development of muscle weakness in patients with PAH. GDF-15 levels may be important in allowing us to define which patients have muscle weakness. In the future we aim to perform a clinical trial of drugs which block the actions of GDF-15.