Prospective Open-Label Trial of Rituximab for Primary Pulmonary Alveolar Proteinosis Investigator-Initiated Study
UMCIRB#: 05-354
Supported by: Genentech, Incorporated
PI: Mary Jane Thomassen, Ph.D.
Sub-Investigator(s): Mani S. Kavuru, MD
Study Coordinator: Irene Marshall, PA-C, CCRC
Contact: (252) 744-5888 (p), (252) 744-4887 (f)
Email: ECU_PAP_REGISTRY@ecu.edu
The goal of this study is to conduct a prospective, open-label 6-month trial of rituximab in patients who present with symptomatic primary or idiopathic PAP. A total of 10 subjects with primary PAP will be evaluated over 12 months at East Carolina University. Patients over age 18 with a clinical diagnosis of moderate symptomatic idiopathic PAP, established by appropriate clinical history, radiographic and physiologic findings, presence of circulating anti-GM-CSF antibody, and confirmatory findings on bronchoscopy with bronchoalveolar lavage and/or open-lung biopsy will be recruited. Patients with newly diagnosed PAP or established disease may be considered for this study.
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Studies in Lung Biology Collection of Material for Tissue Banking
UMCIRB#: 05-354
Supported by: Genentech, Incorporated
PI: Mary Jane Thomassen, Ph.D.
Sub-Investigator(s): Mani S. Kavuru, MD
Study Coordinator: Irene Marshall, PA-C, CCRC
Contact: (252) 744-5888 (p), (252) 744-4887 (f)
Email: ECU_SARCOID_REGISTRY@ecu.edu
At East Carolina University, there is a research effort to understand the biological circumstances that lead to lung disease. As a result, there are several studies being performed that involve different groups of investigators. This is due to the fact that lung diseases are associated with many biological factors which require a “team” approach for investigation. Since several studies involve the use of blood and lung cells obtained during bronchoscopy and residual tissue from lung surgery, we are establishing a “tissue bank” of these specimens. Subjects for these studies will be: 1) patients who come to our Pulmonary Outpatient Clinic for diagnosis and treatment of lung disease 2) patients who undergo surgery for lung disease and 3) healthy volunteers (controls) who are recruited for this study through advertisement. The subjects may be cigarette smokers. Normal volunteers should be free of acute or chronic respiratory symptoms.
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In Vitro Generation of GM-CSF Monoclonal Neutralizing Antibodies
UMCIRB#: 05-354
Supported by: Genentech, Incorporated
PI: Mary Jane Thomassen, Ph.D.
Sub-Investigator(s): Mani S. Kavuru, MD
Study Coordinator: Irene Marshall, PA-C, CCRC
Contact: (252) 744-5888 (p), (252) 744-4887 (f)
The objective of this study is to generate proof-of-principle fully human antibodies (HuMabs) specific to GM-CSF that can be optimized for affinity or production using Morphotek’s technology. Patients with Pulmonary Alveolar Proteinosis (PAP) have high levels of circulating anti-GM-CSF autoantibodies that are believed to mediate this lung disorder. This study will utilize lymphocytes from the peripheral blood of 15 patients with PAP to help develop humanized monoclonal antibodies directed at GM-CSF in the laboratory. Only subjects with a confirmed diagnosis of pulmonary alveolar proteinosis and an anti GM-CSF titer are eligible for this study.
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Cytokine Dysregulation in GM-CSF Autoimmunity
UMCIRB#: 05-354
Supported by: Genentech, Incorporated
PI: Mary Jane Thomassen, Ph.D.
Sub-Investigator(s): Mani S. Kavuru, MD
Study Coordinator: Irene Marshall, PA-C, CCRC
Contact: (252) 744-5888 (p), (252) 744-4887 (f)
The long-term objective of this study is to delineate the relationships among immune cells, cytokines and anti-GM-CSF autoantibody in PAP pathophysiology. This study will use banked blood samples and banked tissue from bronchoscopy and, therefore, allow the study of lung fluids and cells, as well as systemic cells and mediators from blood. This protocol will enroll 10 patients with PAP being treated with Rituximab under the protocol “Prospective Open-Label Trial for Primary Pulmonary Alveolar Proteinosis,” 20 untreated healthy controls for a single bronchoscopy, and 70 untreated healthy controls for a single venous blood draw. The 10 PAP patients will be 18 years of age or older from throughout the United States who have been diagnosed with primary PAP (PAP that develops for unknown reasons).
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PPARg Dysfunction in Sarcoidosis
UMCIRB#: 05-0631
Supported by: National Institutes of Health
PI: Mary Jane Thomassen, Ph.D.
Sub-Investigator(s): Mani S. Kavuru, MD
Study Coordinator: Irene Marshall, PA-C, CCRC
Contact: (252) 744-5888 (p), (252) 744-4887 (f)
The specific aims of this study are to: (1) Evaluate intrinsic PPARg mRNA (by real time RT-PCR) and protein expression (by immunoblotting and immunocytochemistry) in pulmonary granuloma tissue and bronchoalveolar lavage (BAL) cells; (2) Investigate in vitro PPARg responses of BAL and peripheral blood cells to challenge with positive (interleukin 4 [IL-4], granulocyte-macrophage colony stimulating factor [GM-CSF]), phorbol myristate acetate [PMA]); and negative (PPARg ligands, IFNg) regulators of PPARg; and (3) Determine by sequence analysis whether PPARg polymorphisms are associated with sarcoidosis. The study will use a combination of specimens from sarcoidosis patients vs healthy controls to characterize the status of PPARg in sarcoidosis.
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