Active clinical trials for "Familial Primary Pulmonary Hypertension"

This is an open-label, multicenter, parallel, randomized (1:1 Slow Dose Titration Group; Rapid Dose Titration Group), two-group study to evaluate the safety, tolerability, pharmacokinetics and efficacy of slow and rapid dose titration regimens of subcutaneous Remodulin infusion in subjects with pulmonary arterial hypertension (PAH). The study will include about 50 subjects at up to 10 clinical trial centers in China. The treatment phase of the study will last approximately 16 weeks. Subjects who complete all required assessments will also be eligible to enter a long-term open-label, extension study (CVT-CV-004).

Pulmonary arterial hypertension (PAH) is a disorder of elevated pulmonary vascular resistance characterized by progressive remodeling and obliteration of vessels of the distal pulmonary circulation. Outcomes in PAH could be improved with earlier diagnosis, and with the early deployment of therapies before irreversible changes have occurred. This study tests the sensitivity of positron emission tomography (PET)-CT scanning with [89Zr]-bevacizumab, a radioisotope-conjugated anti-VEGF antibody for detecting pulmonary vascular remodeling in PAH disease. This test could enable non-invasive diagnosis early in the course of the disease, and potentially improve outcomes in PAH,

Pulmonary arterial hypertension (PAH) is a serious and eventually fatal disease damaging the lungs and the heart. It results from narrowing and eventual blockage of small blood vessels in the lung, due to abnormal proliferation of cells in the blood vessel (arterial). Patients with PAH suffer from fatigue, shortness of breath, low oxygen levels, blood clots and heart failure. No therapies reverse the disease process in the lung arteries, however there are three approved drugs that can temporarily dilate the vessels and improve symptoms. However, all three drugs have significant side effects and toxicities, they do not work effectively in many patients, survival remains on average only 2 to 3 years once symptoms begin, and none of these drugs prevent the underlying disease process in the small arteries of the lung. PAH is known to develop in patients with a pre-existing class of bone marrow diseases called myeloproliferative disorders (MPDs). We and others have recently shown that patients with PAH have bone marrow changes similar to those seen in patients with MPDs, even without other signs and symptoms of those bone marrow diseases such as anemia or high platelet and white blood cell counts. Compared to healthy volunteers, patients with PAH have a higher frequency of immature stem and progenitor cells able to produce blood cells and vascular wall cells in their bone marrow. They also have higher circulating numbers of these cells in the blood, and increased localization of these cells in the lung blood vessels. When immature bone marrow cells from PAH patients and normal volunteers were infused into mice, the mice receiving PAH marrow cells developed similar lung and heart problems to PAH patients, suggesting that the bone marrow problem is a primary cause of the lung problems, and that the increased numbers of immature bone marrow cells in the bone marrow and blood of PAH patients causes the lung blood vessel disease. The drug hydroxyurea is used to inhibit the abnormally high level of bone marrow cell proliferation in patients with MPDs. It has been shown to reduce the numbers of circulating immature bone marrow cells in patients with MPDs. Hydroxyurea has been available for almost fifty years, and has been used to treat patients with MPDs, sickle cell anemia, and congenital heart disease for very prolonged periods of time, up to twenty or more years in individual patients. It has an excellent long-term safety profile and few side effects and is generally well tolerated. It does not appear to result in an increased rate of leukemia even with many years of treatment. In the current protocol, we hypothesize that treating patients with PAH with hydroxyurea will decrease the level of circulating immature bone marrow cells and interrupt the abnormal narrowing and occlusion of lung arteries. We will treat patients with moderately severe primary (no known underlying cause) PAH with 6 months of hydroxyurea, carefully monitoring side effects and adjusting dosage as necessary, and measure the effect on circulating immature cells, lung blood vessel pressures, other blood markers of active PAH, and exercise tolerance.

To evaluate the effect of inhaled treprostinil compared to placebo on exercise capacity and time to clinical worsening.

This is a multicenter, randomized (2:1 oral treprostinil: placebo), double-blind, placebo-controlled study in subjects with Pulmonary Arterial Hypertension (PAH) who are currently receiving background dual therapy (ambrisentan, tadalafil) for at least 30 days at randomization for their PAH. Once randomized, subjects will return for 5 study visits up to Week 28 during the blinded period. After the Week 28 Visit, eligible subjects will transition to the open-label period of the study for up to 20 weeks.

Study to evaluate the efficacy, safety, tolerability and pharmacokinetics of JTT-251 administered for 24 weeks in participants with pulmonary arterial hypertension (PAH)

Activity-related dyspnoea appears to be the earliest and the most frequent complaint for which patients with PAH seek medical attention. This symptom progresses relentlessly with time leading invariably to avoidance of activity with consequent skeletal muscle deconditioning and an impoverished quality of life. Unfortunately, effective management of this disabling symptom awaits a better understanding of its underlying physiology. Our team has recently showed that PAH patients may exhibit reduced expiratory flows at low lung volumes at spirometry (namely instantaneous forced expiratory flows measured after 50% and 75% of the FVC has been exhaled [FEF50% and FEF75%] lower than predicted), despite a preserved forced expiratory volume in 1 second/forced vital capacity ratio (FEV1/FVC) . Several studies have shown that such a finding ("small airway disease") could be common in certain PAH cohorts, have either related it to incidental descriptions of airway wall thickening with lymphocytic infiltration in PAH or proposed several other speculative explanatory mechanisms, either biological or mechanical. Whatever its cause, reduced expiratory flows at low lung volumes imply that the operating tidal volume (VT) range becomes closer than normally to residual volume (RV) mostly through an increase in RV (elevated residual volume/total lung capacity ratio, RV/TLC). The reduced difference between forced and tidal expiratory flows promotes dynamic lung hyperinflation [i.e., a progressive increase in end-expiratory lung volume (EELV)] under conditions of increased ventilatory demand. Dynamic lung hyperinflation (DH) is well known to have serious sensory consequences, i.e., increase in dyspnoea intensity, as clearly shown in patients with chronic obstructive pulmonary disease and chronic heart failure. The aim of this study is to evaluate whether administration of inhaled BDs (β2-agonist and/or anticholinergic), as add-ons to vasodilators, would be beneficial to PAH patients by reducing and/or delaying the rate of onset of DH, thus ameliorating the exertional symptoms in patients with stable PAH undergoing high-intensity constant work-rate (CWR) cycle endurance test. This is a randomised double-blind placebo-controlled crossover study. Design: 5 visits; V1: screening, familiarization, incremental cardiopulmonary exercise testing (CPET); V2: constant work-rate (CWR-CPET); V3, V4 and V5: CWR-CPET after intervention, in a random order: Placebo (P), Ipratropium Bromide (IB), Ipratropium Bromide + Salbutamol (IB+SALB).

The primary purpose of this study is to compare the number of participants with reversible pulmonary hypertension (vasoreactivity) due to nitric oxide for inhalation and oxygen as compared to 100% oxygen.

The investigators hypothesize that baseline plasma brain natriuretic peptide (BNP) and migration inhibitory factor (MIF) levels are surrogate markers of clinical severity of PAH and that changes in plasma brain natriuretic peptide (BNP) and MIF levels pre and post exercise.

The purpose of this study is to determine if cardizem is effective in the treatment of nitric oxide non-responder pulmonary arterial hypertension.