Active clinical trials for "Pulmonary Alveolar Proteinosis"

Clinical trial for subjects with autoimmune pulmonary alveolar proteinosis (aPAP) who have completed the IMPALA trial (NCT02702180). At the Baseline visit, eligible subjects may continue or re-start treatment with 300 µg inhaled molgramostim (recombinant human Granulocyte-Macrophage Colony Stimulating Factor; GM-CSF) administered intermittently in cycles of seven days molgramostim, administered once daily, and seven days off treatment. Subject will be treated with inhaled molgramostim for up to 36 months. During the trial, whole lung lavage will be applied as rescue therapy.

The purpose of this study is to determine the safety and tolerance of an oral administration of methionine in the treatment of pulmonary alveolar proteinosis due to the double mutation Ala393Thr / Ser567Leu in the MARS gene. This disease is very severe and especially leads to chronic respiratory insufficiency. There is no curative treatment for this disease. The MARS gene encodes the methionine tRNA synthetase (MetRS). Mutations in this gene leads to a defect in MetRS function. In cultured mutated yeast, addition of methionine in culture medium restores MetRS function. Therefore, the investigators hypothesized that treatment of patients with methionine could have beneficial effects on the disease.

This study evaluates inhaled molgramostim (recombinant human granulocyte macrophage-colony stimulating factor [rhGM-CSF]) in the treatment of autoimmune pulmonary alveolar proteinosis (aPAP) patients. A third of the patients will receive inhaled molgramostim once daily for 24 weeks, a third will receive inhaled molgramostim intermittently (7 days on, 7 days off) for 24 weeks and a third will receive inhaled matching placebo for 24 weeks.

Background: Healthy people have white blood cells that protect them against bacteria, viruses, and fungi. However, some people have diseases which cause the body to make white blood cells that do not work properly. These white blood cells can attack the body s own proteins. These types of diseases are called anti-cytokine autoantibody-associated diseases. They can cause severe illnesses and even death. They are also difficult to treat with standard drugs. Rituximab is a drug used to treat rheumatoid arthritis. It attacks white blood cells that do not work properly. Currently, it is not approved for treating anti-cytokine autoantibody-associated diseases. However, researchers think that it may be able to help treat people with these immune diseases. Objectives: - To see if rituximab is a safe and effective treatment for anti-cytokine autoantibody-associated diseases. Eligibility: Individuals at least 18 years of age who have anti-cytokine autoantibody-associated diseases. Participants must also be enrolled in a related immune disorder study at the National Institutes of Health. Design: The study will last 24 months. Participants will take rituximab for 6 months and have follow-up visits for the remaining 18 months. Participants will be screened with a physical exam and medical history. Blood and urine samples will be collected. Other samples will be collected as needed if participants currently have an infection. Participants will enter the hospital for 1 week at the start of treatment. They will have four doses of rituximab given 2 days apart. This first treatment will be monitored with frequent blood tests. Over the next 6 months, participants will have four more doses of rituximab given about 1 month apart. Treatment will be monitored with frequent blood tests and sample collections as needed. There will be four follow-up study visits at 3, 6, 12, and 18 months after the last dose of rituximab.

The purpose of this study is to evaluate the therapeutic efficacy of inhaled recombinant human GM-CSF in individuals with hereditary Pulmonary Alveolar Proteinosis (PAP) due to partial dysfunction of the GM-CSF receptor.

The purpose of this study is to determine whether the use of rituximab is effective in treating pulmonary alveolar proteinosis by leading to an improvement in lung function and disease status.

This is a prospective, randomized, open-label, long-term, phase 2 study of inhaled granulocyte/macrophage-colony stimulating factor following whole lung lavage therapy in patients with autoimmune pulmonary alveolar proteinosis.

This is a randomized, double-blind, placebo-controlled, single ascending (SAD), and multiple ascending dose (MAD) study conducted at a single clinical site within the UK. Healthy male and female subjects (on non-child bearing potential) will be enrolled to investigate single inhaled doses of molgramostim at 3 dose levels (Part 1) and multiple inhaled doses at 2 dose levels (Part 2). The 2 doses in the multiple ascending dose regimens will be administered once daily (QD) for 6 consecutive days. The clinical indication for inhaled molgramostim is the treatment of respiratory diseases such as aPAP, bronchiectasis and cystic fibrosis. The Clinical trial will involve 42 healthy participants. The trial is expected to last approximately 4 months.

Objective: Evaluate Pharmacokinetics and determine the safety of GM-CSF single dose inhalation. Study Design: Pharmacokinetic open study

Pulmonary alveolar proteinosis (PAP) is a syndrome of surfactant accumulation, respiratory failure, and innate immune deficiency for which therapy remains limited to whole lung lavage (WLL), an invasive physical procedure to remove surfactant unavailable at most medical centers. While PAP occurs in multiple diseases affecting men, women, and children of all ages and ethnic origins, in 85% of patients, it occurs as an idiopathic disease associated with neutralizing GM-CSF autoantibodies. Basic science and translational research has shown that idiopathic PAP is an autoimmune disease in which disruption of GM-CSF signaling impairs the ability of alveolar macrophages to clear surfactant and perform host defense functions. Recently, it has been shown that cholesterol toxicity drives pathogenesis in alveolar macrophages from GM-CSF deficient (Csf2-/-) mice and patients with autoimmune PAP. Loss of GM-CSF signaling reduces PU.1/CEBP-mediated expression of PPARγ and its downstream target ABCG1 (a cholesterol exporter important in macrophages). The cell responds by esterifying and storing cholesterol in vesicles to reduce toxicity. Eventually, vesicles fill the cell, impair intracellular transport and reduce uptake and clearance of surfactant from the lung surface resulting in disease manifestations. Recent data indicates that pioglitazone, a PPARγ agonist currently approved by the FDA for human use, increases cholesterol/surfactant clearance by alveolar macrophages from autoimmune PAP patients and Csf2-/- mice. Importantly, pioglitazone significantly reduced the severity of PAP lung disease in Csf2-/- mice after several months of therapy. Together, these observations suggest pioglitazone could be 'repurposed' as pharmacologic therapy for PAP.