Ignite Creation Date:
2025-12-24 @ 9:43 PM
Ignite Modification Date:
2026-02-23 @ 4:35 PM
Study NCT ID:
NCT00923832
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2009-06-17
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Early Molecular Detection for the Improved Diagnosis of Invasive Pulmonary Aspergillosis and Invasive Pulmonary Zygomycosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055744', 'term': 'Invasive Pulmonary Aspergillosis'}, {'id': 'D009181', 'term': 'Mycoses'}], 'ancestors': [{'id': 'D055732', 'term': 'Pulmonary Aspergillosis'}, {'id': 'D001228', 'term': 'Aspergillosis'}, {'id': 'D001423', 'term': 'Bacterial Infections and Mycoses'}, {'id': 'D007239', 'term': 'Infections'}, {'id': 'D000072742', 'term': 'Invasive Fungal Infections'}, {'id': 'D008172', 'term': 'Lung Diseases, Fungal'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE'}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-03-30'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2009-11-23', 'completionDateStruct': {'date': '2009-11-23'}, 'lastUpdateSubmitDate': '2017-06-30', 'studyFirstSubmitDate': '2009-06-17', 'studyFirstSubmitQcDate': '2009-06-17', 'lastUpdatePostDateStruct': {'date': '2017-07-02', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2009-06-18', 'type': 'ESTIMATED'}}, 'conditionsModule': {'keywords': ['Fungal Infections', 'PCR Assays', 'Cell Wall Derived Biomarkers', 'EORTC/MSG Definitions', 'Molecular Assays', 'Lung Fungal Infection', 'Invasive Pulmonary Fungal Infection', 'Invasive Pulmonary Aspegillosis', 'Invasive Pulmonary Zycomycosis'], 'conditions': ['Immunocompromised Host', 'Invasive Pulmonary Fungal Infection', 'Invasive Pulmonary Aspergillosis', 'Invasive Pulmonary Zygomycosis']}, 'referencesModule': {'references': [{'pmid': '10747121', 'type': 'BACKGROUND', 'citation': 'Becker MJ, de Marie S, Willemse D, Verbrugh HA, Bakker-Woudenberg IA. Quantitative galactomannan detection is superior to PCR in diagnosing and monitoring invasive pulmonary aspergillosis in an experimental rat model. J Clin Microbiol. 2000 Apr;38(4):1434-8. doi: 10.1128/JCM.38.4.1434-1438.2000.'}, {'pmid': '9815229', 'type': 'BACKGROUND', 'citation': "Cenci E, Mencacci A, Fe d'Ostiani C, Del Sero G, Mosci P, Montagnoli C, Bacci A, Romani L. Cytokine- and T helper-dependent lung mucosal immunity in mice with invasive pulmonary aspergillosis. J Infect Dis. 1998 Dec;178(6):1750-60. doi: 10.1086/314493."}, {'pmid': '16552065', 'type': 'BACKGROUND', 'citation': 'Cortez KJ, Lyman CA, Kottilil S, Kim HS, Roilides E, Yang J, Fullmer B, Lempicki R, Walsh TJ. Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus. Infect Immun. 2006 Apr;74(4):2353-65. doi: 10.1128/IAI.74.4.2353-2365.2006.'}]}, 'descriptionModule': {'briefSummary': "Background:\n\n* Fungal infections of the lung (pneumonia) can be caused by molds, such as Aspergillus and Zygomycetes, but these causes are often difficult for a doctor to diagnose. Early and accurate diagnosis of these infections can help doctors to select the correct medicines for proper treatment.\n* A number of methods are used to diagnose fungal pneumonia. Ones that are commonly used in clinical practice include radiographic imaging (chest X-rays and computed tomography (CT) scans), blood tests, and cultures taken from fluid from the lungs (broncho-alveolar lavage (BAL) fluid). Other new methods may improve the diagnosis of fungal pneumonias. These methods include tests that can detect DNA from the fungal germ in blood and BAL fluid of some patients with these infections.\n\nObjectives:\n\n* To help develop better and more accurate methods of diagnosing fungal lung infections.\n* To detect fungal DNA and chemicals in the bloodstream and BAL fluid of immunocompromised patients with pneumonia.\n\nEligibility:\n\n\\- Immunocompromised patients who are currently enrolled in another NIH protocol and who have a CT scan that shows a possible fungal infection of the lung.\n\nDesign:\n\n* Researchers will review patients' existing medical records and CT scans, and current pneumonia treatment plans.\n* Patients will provide blood and BAL samples for the duration of their treatment for pneumonia, as required by researchers. Additional CT scans will not be performed, except as part of existing treatment plans.", 'detailedDescription': "Background:\n\nInvasive fungal infections are an important cause of infectious disease, morbidity and mortality in immunocompromised patients with cancer, hematopoietic stem cell transplantation, aplastic anemia, autoimmune diseases, and primary immune deficiencies.\n\nForemost among the more lethal of these infections are invasive pulmonary aspergillosis and zygomycosis. Early detection of these infections allows timely initiation of specific antifungal therapy, which may be life saving. However, early diagnosis of respiratory fungal infections is difficult, often leading to delay in therapy and inaccurate treatment.\n\nThe Immunocompromised Host Section has developed a series of sensitive and highly specific PCR assays for the detection of these life-threatening infections. We also have characterized the expression of cell wall derived biomarkers, (1-3)-Beta-D-glucan and galactomannan in vitro and in vivo. Laboratory animal studies indicate that these assays may complement current diagnostic modalities and allow for more accurate and earlier detection of invasive pulmonary fungal infections in immunocompromised patients.\n\nObjectives:\n\nThe primary objective of this study is to improve the early diagnosis of invasive pulmonary aspergillosis and invasive pulmonary zygomycosis in immunocompromised patients through the addition of molecular biomarker detection methodology to the standard diagnostic systems used in clinical microbiology laboratories.\n\nThe secondary objectives are:\n\nA. To compare the diagnostic yield and analytical performance of the PCR, galactomannan and (1-3)-Beta-D-glucan to standard diagnostic systems.\n\nB. To evaluate the effect of different independent variables on expression of the aforementioned assays\n\nC. To characterize the variables that may contribute to therapeutic outcome (global response; survival)\n\nD. To characterize the use of these biomarkers in the context of EORTC/MSG definitions\n\nE. To identify genetic markers which may predispose patients to invasive fungal pulmonary infections.\n\nEligibility:\n\nImmunocompromised patients currently enrolled in any NIH IRB approved Clinical Center protocol for the evaluation and/or treatment of his/her primary disease, or patients receiving treatment at the Children's National Medical Center (CNMC) who develop a pulmonary infiltrate radiologically compatible with invasive pulmonary aspergillosis or invasive pulmonary zygomycosis, by EORTC/MSG criteria.\n\nDesign:\n\nThis is a multi-center, prospective diagnostic interventional study.\n\nPatients referred to the Clinical Center for evaluation and treatment in primary research protocols will be eligible for enrollment in this protocol at the Clinical Center. Patients meeting eligibility criteria may also be enrolled from the CNMC.\n\nPatients who have compatible radiologic signs and are at risk for development of invasive pulmonary aspergillosis and invasive pulmonary zygomycosis will have specimens of bronchoalveolar lavage (BAL) fluid supernatant and /or tissue from lung biopsy when available, obtained for the measurement of diagnostic PCR for Aspergillus and Zygomycete identification, proteomics, cytokines and for the presence of galactomannan and (1-3)-Beta-D-glucan. The BAL will be performed only if clinically indicated as part of the patient's routine care of pneumonic infiltrates.\n\nBlood will be obtained from patients meeting the eligibility requirements, regardless of whether they have had a BAL or lung tissue biopsy, to be submitted for the measurement of diagnostic PCR for Aspergillus and Zygomycete identification, proteomics, cytokines, presence of galactomannan and (1-3)-Beta-D-glucan and host genomics.\n\nDigital copies of computer tomography (CT) images, that are part of routine care will utilized to reconstruct multi-dimensional volumetric images and correlate clinical and laboratory outcomes with the extent of lung volume involvement.\n\nBackground:\n\nInvasive fungal infections are an important cause of infectious disease, morbidity and mortality in immunocompromised patients with cancer, hematopoietic stem cell transplantation, aplastic anemia, autoimmune diseases, and primary immune deficiencies.\n\nForemost among the more lethal of these infections are invasive pulmonary aspergillosis and zygomycosis. Early detection of these infections allows timely initiation of specific antifungal therapy, which may be life saving. However, early diagnosis of respiratory fungal infections is difficult, often leading to delay in therapy and inaccurate treatment.\n\nThe Immunocompromised Host Section has developed a series of sensitive and highly specific PCR assays for the detection of these life-threatening infections. We also have characterized the expression of cell wall derived biomarkers, (1-3)-Beta-D-glucan and galactomannan in vitro and in vivo. Laboratory animal studies indicate that these assays may complement current diagnostic modalities and allow for more accurate and earlier detection of invasive pulmonary fungal infections in immunocompromised patients.\n\nObjectives:\n\nThe primary objective of this study is to improve the early diagnosis of invasive pulmonary aspergillosis and invasive pulmonary zygomycosis in immunocompromised patients through the addition of molecular biomarker detection methodology to the standard diagnostic systems used in clinical microbiology laboratories.\n\nThe secondary objectives are:\n\nA. To compare the diagnostic yield and analytical performance of the PCR, galactomannan and (1-3)-Beta-D-glucan to standard diagnostic systems.\n\nB. To evaluate the effect of different independent variables on expression of the aforementioned assays\n\nC. To characterize the variables that may contribute to therapeutic outcome (global response; survival)\n\nD. To characterize the use of these biomarkers in the context of EORTC/MSG definitions\n\nE. To identify genetic markers which may predispose patients to invasive fungal pulmonary infections.\n\nEligibility:\n\nImmunocompromised patients currently enrolled in any NIH IRB approved Clinical Center protocol for the evaluation and/or treatment of his/her primary disease, or patients receiving treatment at the Children's National Medical Center (CNMC) who develop a pulmonary infiltrate radiologically compatible with invasive pulmonary aspergillosis or invasive pulmonary zygomycosis, by EORTS/MSG criteria.\n\nDesign:\n\nThis is a multi-center, prospective diagnostic interventional study.\n\nPatients referred to the Clinical Center for evaluation and treatment in primary research protocols will be eligible for enrollment in this protocol at the Clinical Center. Patients meeting eligibility criteria may also be enrolled from the CNMC.\n\nPatients who have compatible radiologic signs and are at risk for development of invasive pulmonary aspergillosis and invasive pulmonary zygomycosis will have specimens of bronchoalveolar lavage (BAL) fluid supernatant and /or tissue from lung biopsy when available, obtained for the measurement of diagnostic PCR for Aspergillus and Zygomycete identification, proteomics, cytokines and for the presence of galactomannan and (1-3)-Beta-D-glucan. The BAL will be performed only if clinically indicated as part of the patient's routine care of pneumonic infiltrates.\n\nBlood will be obtained from patients meeting the eligibility requirements, regardless of whether they have had a BAL or lung tissue biopsy, to be submitted for the measurement of diagnostic PCR for Aspergillus and Zygomycete identification, proteomics, cytokines, presence of galactomannan and (1-3)-Beta-D-glucan and host genomics.\n\nDigital copies of computer tomography (CT) images, that are part of routine care will be utilized to reconstruct multi-dimensional volumetric images and correlate clinical and laboratory outcomes with the extent of lung volume involvement."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT', 'OLDER_ADULT'], 'maximumAge': '99 Years', 'minimumAge': '1 Year', 'healthyVolunteers': False, 'eligibilityCriteria': "* INCLUSION CRITERIA:\n\nPatients currently enrolled in any NIH IRB approved Clinical Center protocol or under treatment at the CNMC who are undergoing bronchoscopy or lung biopsy for diagnosis of possible invasive pulmonary aspergillosis or invasive pulmonary zygomycosis.\n\nInformed consent of the patient or the patient's legally authorized representative.\n\nFulfillment of one or more of the following EORTC/MSG host criteria:\n\n* History of neutropenia (ANC \\< 500/mm(3)) within the past 3 months temporally related to the onset of radiographic changes\n* Receipt of an allogeneic HSCT\n* Receipt of solid organ transplantation\n* Prolonged use of corticosteroids at an average minimum dose of 0.3 mg/kg/day prednisone equivalent for \\> 3 weeks\n* Treatment with other recognized T-cell immune suppressants such as cyclosporine, TNF alpha blockers, specific monoclonal antibodies such as alemtuzumab, nucleoside analogues during the past 90 days\n* Myelodysplastic syndrome\n* Severe aplastic anemia\n* Cushing's disease\n* HIV/AIDS\n* Primary immunodeficiencies (such as chronic granulomatous disease, severe combined immunodeficiency)\n\nThe presence of one or more of the following signs on chest CT or radiograph:\n\n* Dense well circumscribed lesions with or without a halo sign\n* Air crescent sign\n* Cavity\n* Focal, segmental or lobar infiltrates\n\nEXCLUSION CRITERIA:\n\nInterstitial or diffuse infiltrates on chest CT or radiograph\n\nInability to provide informed consent\n\nChildren weighing less than 10 kg\n\nAny other concomitant condition, which in the opinion of the investigator would place the patient at risk by participating in the study"}, 'identificationModule': {'nctId': 'NCT00923832', 'briefTitle': 'Early Molecular Detection for the Improved Diagnosis of Invasive Pulmonary Aspergillosis and Invasive Pulmonary Zygomycosis', 'organization': {'class': 'NIH', 'fullName': 'National Institutes of Health Clinical Center (CC)'}, 'officialTitle': 'Early Molecular Detection for the Improved Diagnosis of Invasive Pulmonary Aspergillosis and Invasive Pulmonary Zygomycosis', 'orgStudyIdInfo': {'id': '090109'}, 'secondaryIdInfos': [{'id': '09-C-0109'}]}, 'contactsLocationsModule': {'locations': [{'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Childrens National Medical Center', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '20892', 'city': 'Bethesda', 'state': 'Maryland', 'country': 'United States', 'facility': 'National Institutes of Health Clinical Center, 9000 Rockville Pike', 'geoPoint': {'lat': 38.98067, 'lon': -77.10026}}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'National Cancer Institute (NCI)', 'class': 'NIH'}}}}