[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT00001352":3,"trial-entities:NCT00001352":143,"trial-summary:NCT00001352":148},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":9,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":23,"study_type":28,"primary_purpose":9,"phases":29,"enrollment_info":30,"interventions":33,"primary_outcomes":34,"secondary_outcomes":38,"sex":45,"minimum_age":46,"maximum_age":47,"healthy_volunteers":48,"eligibility_criteria":49,"std_ages":61,"locations":64,"central_contacts":84,"overall_officials":89,"references":92,"see_also_links":139},"NCT00001352","930106","Fungal Infection Susceptibility","Cryptococcosis in Previously Healthy Adults","RECRUITING",null,"2026-06-03","2026-08-04","1993-04-01","National Institute of Allergy and Infectious Diseases (NIAID)","NIH","The protocol will be carried out in accordance with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) and the following United States Code of Federal Regulations (CFR) applicable to clinical studies: 45 CFR Part 46, 21 CFR Part 50, 21 CFR Part 56, 21 CFR Part 312, and\u002For 21 CFR Part 812.\n\nNIH-funded investigators and study site staff who are responsible for the conduct, management, or oversight of NIH-funded studies have completed Human Subjects Protection and ICH GCP Training.\n\nThe protocol, informed consent form(s), recruitment materials, and all participant materials will be submitted to the Institutional Review Board (IRB) for review and approval. Approval of both the protocol and the consent form must be obtained before any participant is enrolled. Any amendment to the protocol will require review and approval by the IRB before the changes are implemented to the study. In addition, all changes to the consent form will be approved by the IRB; an IRB determination will be made regarding whether a new consent needs to be obtained from participants who provided consent, using a previously approved consent form.\n\n...","Cryptococcus is a fungus that causes infections most commonly in immunocompromised patients, such as those with AIDS and solid organ transplant recipients, particularly renal transplant recipients (1-3). However, approximately one-third of cases fall outside these groups and, overall, 12.9 percent to 17.9 percent have no readily identifiable immune defect (4, 5). The genetic factors, which may predispose to cryptococcosis and the immune response in these patients, have not been extensively studied.\n\nThis protocol is designed to examine the immune deficits that predispose to cryptococcosis as well as the clinical and immune responses among previously healthy adults. The patients included will have an unknown predisposing condition and cryptococcosis. Patients will undergo various sampling procedures, including saliva, blood, eyebrow hair, CSF, and nail clipping collection. Throughout the study, patients will be provided with standard medical care and will be seen as often as necessary to manage their condition. Patients in whom microbiologic control of the infection has occurred but in whom inflammation is causing neurologic damage may be treated with corticosteroids or other immunosuppressive agents. Genetically related family members of patients will also be screened for clinical, in vitro, immune, and genetic correlates of immune abnormalities. Healthy adult volunteers, as a comparison group, will be enrolled as a source of blood samples, saliva samples, CSF samples, and eyebrow hair samples for research testing. Moreover, with respect to cryptococcosis, patients with isolated non-central nervous system (CNS) disease (e.g., pulmonary) may serve as a subset comparator to those with CNS involvement-a major tissue tropism for Cryptococcus.\n\nGenetic and immunologic testing will be performed on all subjects (patients, relatives, and healthy volunteers) to evaluate for possible immunogenetic factors that lead to susceptibility to cryptococcosis. Among the aims of this protocol are to better understand the pathophysiology and genetic factors that lead to defects in host defense and to use modern and evolving methods in molecular and cellular biology to elucidate the pathogenesis of this particular susceptibility. A better understanding of the underlying pathophysiology of immune defects and genetic susceptibility to fungal infections could allow for the rational development of novel therapies for such diseases and to benefit future patients.",[18,19,20,21,22],"Cryptococcal Infection","Cryptococcal Pneumonia","Pulmonary Cryptococcosis","Cryptococcal Meningitis","Cryptococcosis",[24,25,26,27],"Natural History","Cryptococcus","Cryptococcus Neoformans","Cryptococcus gattii","OBSERVATIONAL",[],{"count":31,"type":32},800,"ESTIMATED",[],[35],{"measure":36,"timeFrame":37},"Characterize the full spectrum of clinical disease of Cryptococcosis in previously healthy adults without known immune predisposition.","1-5 years",[39,41,43],{"measure":40,"timeFrame":37},"Characterize the immunological and genetic mechanisms predisposing to disease acquisition.",{"measure":42,"timeFrame":37},"Understand the inflammatory response and distinguish its consequences from those directly due to fungal growth.",{"measure":44,"timeFrame":37},"Understand the natural history of disease progression or regression over time.","ALL","18 Years","99 Years",true,{"inclusion":50,"exclusion":54,"raw_text":60},[51,52,53],"histopathology showing cryptococci; or","culture of C. neoformans or C. gattii","a positive cryptococcal antigen in the serum and\u002For CSF, together with CSF cell count and chemistry consistent with cryptococcal meningitis. 2. Be over the age of 18 years old. 3. Have a primary physician outside of the NIH. 4. Agree to undergo genetic testing that will include WES and high density SNP arrays as appropriate for possible WES linkage studies. 5. Allow samples to be stored for future research. 6. Pregnant patients will not be excluded. However, research procedures greater than minimal risk including bone marrow biopsy and apheresis would not be performed on pregnant subjects. Otherwise, pregnant patients with cryptococcus would be treated with as per standard of care, minimizing teratogenic potential of drugs and ionizing radiation whenever possible.",[55,56,57,58,59],"HIV","Cancer chemotherapeutic agent(s)","An underlying malignancy could be grounds for possible exclusion of a patient if, in the opinion of the investigator, the underlying disease predisposed the patient to the infection","Monoclonal antibody therapy directed against a patient s immune system 2. Any condition that in the opinion of the investigator may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol. For example, we may exclude patients with Cushing s disease that have very high cortisol levels at the time of diagnosis of their cryptococcosis.","Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.","* INCLUSION CRITERIA:\n\nPatients\n\nPatients must:\n\n1. Have cryptococcosis as determined by information collected from their medical records, telephone interviews, or from a referring physician:\n\n   * histopathology showing cryptococci; or\n   * culture of C. neoformans or C. gattii\n   * a positive cryptococcal antigen in the serum and\u002For CSF, together with CSF cell count and chemistry consistent with cryptococcal meningitis.\n2. Be over the age of 18 years old.\n3. Have a primary physician outside of the NIH.\n4. Agree to undergo genetic testing that will include WES and high density SNP arrays as appropriate for possible WES linkage studies.\n5. Allow samples to be stored for future research.\n6. Pregnant patients will not be excluded. However, research procedures greater than minimal risk including bone marrow biopsy and apheresis would not be performed on pregnant subjects. Otherwise, pregnant patients with cryptococcus would be treated with as per standard of care, minimizing teratogenic potential of drugs and ionizing radiation whenever possible.\n\nBlood Relatives of Patients\n\nBlood relatives must:\n\n1. Be a genetic relative of a patient enrolled in this study\n2. Be over the age of 18 years old\n3. Agree to undergo genetic testing that may include WES and high density SNP analysis\n4. Allow samples to be stored for future research\n\nHealthy Volunteers\n\nHealthy volunteers must:\n\n1. Be between the ages of 18 and 70 years old\n2. Allow samples to be stored for future research\n\nEXCLUSION CRITERIA:\n\nPatients\n\nPatients will be excluded for any of the following:\n\n1. The presence of certain types of acquired abnormalities of immunity due to:\n\n   * HIV\n   * Cancer chemotherapeutic agent(s)\n   * An underlying malignancy could be grounds for possible exclusion of a patient if, in the opinion of the investigator, the underlying disease predisposed the patient to the infection\n   * Monoclonal antibody therapy directed against a patient s immune system\n2. Any condition that in the opinion of the investigator may interfere with the evaluation of a co-existing abnormality of immunity that is the subject of study under this protocol. For example, we may exclude patients with Cushing s disease that have very high cortisol levels at the time of diagnosis of their cryptococcosis.\n\nGenetic Relatives of Patients\n\nGenetic relatives will be excluded for the following:\n\n-Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.\n\nHealthy Volunteers\n\nHealthy volunteers will be excluded for any of the following:\n\n1. HIV or viral hepatitis (B or C).\n2. History of recurrent or severe infections.\n3. History of intravenous drug use.\n4. History of engaging in high-risk activities for exposure to HIV.\n5. Receiving chemotherapeutic agent(s), immunosuppressants or have underlying malignancy.\n6. Pregnancy.\n7. Have history of heart, lung, kidney disease, or bleeding disorders.\n8. Any condition that in the opinion of the investigator may interfere with evaluation of an immune system abnormality that is the subject of study under this protocol.",[62,63],"ADULT","OLDER_ADULT",[65],{"facility":66,"status":8,"city":67,"state":68,"zip":69,"country":70,"contacts":71,"geoPoint":81},"National Institutes of Health Clinical Center","Bethesda","Maryland","20892","United States",[72,77],{"name":73,"role":74,"phone":75,"email":76},"Peter Williamson, MD PhD","CONTACT","301-273-5056","peter.williamson2@nih.gov",{"name":78,"role":74,"phone":79,"email":80},"Tracey-Ann Hoeltermann","(240) 344-8127","tracey-ann.hoeltermann@nih.gov",{"lat":82,"lon":83},38.98067,-77.10026,[85],{"name":86,"role":74,"phone":87,"email":88},"Peter R Williamson, M.D.","(301) 443-8339","williamsonpr@mail.nih.gov",[90],{"name":86,"affiliation":13,"role":91},"PRINCIPAL_INVESTIGATOR",[93,97,100,103,106,109,112,115,118,121,124,127,130,133,136],{"pmid":94,"type":95,"citation":96},"23465017","BACKGROUND","Baddley JW, Forrest GN; AST Infectious Diseases Community of Practice. Cryptococcosis in solid organ transplantation. Am J Transplant. 2013 Mar;13 Suppl 4:242-9. doi: 10.1111\u002Fajt.12116. No abstract available.",{"pmid":98,"type":95,"citation":99},"19182676","Park BJ, Wannemuehler KA, Marston BJ, Govender N, Pappas PG, Chiller TM. Estimation of the current global burden of cryptococcal meningitis among persons living with HIV\u002FAIDS. AIDS. 2009 Feb 20;23(4):525-30. doi: 10.1097\u002FQAD.0b013e328322ffac.",{"pmid":101,"type":95,"citation":102},"20047480","Perfect JR, Dismukes WE, Dromer F, Goldman DL, Graybill JR, Hamill RJ, Harrison TS, Larsen RA, Lortholary O, Nguyen MH, Pappas PG, Powderly WG, Singh N, Sobel JD, Sorrell TC. Clinical practice guidelines for the management of cryptococcal disease: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2010 Feb 1;50(3):291-322. doi: 10.1086\u002F649858.",{"pmid":104,"type":95,"citation":105},"23555970","Brizendine KD, Baddley JW, Pappas PG. Predictors of mortality and differences in clinical features among patients with Cryptococcosis according to immune status. PLoS One. 2013;8(3):e60431. doi: 10.1371\u002Fjournal.pone.0060431. Epub 2013 Mar 26.",{"pmid":107,"type":95,"citation":108},"22937064","Bratton EW, El Husseini N, Chastain CA, Lee MS, Poole C, Sturmer T, Juliano JJ, Weber DJ, Perfect JR. Comparison and temporal trends of three groups with cryptococcosis: HIV-infected, solid organ transplant, and HIV-negative\u002Fnon-transplant. PLoS One. 2012;7(8):e43582. doi: 10.1371\u002Fjournal.pone.0043582. Epub 2012 Aug 24.",{"pmid":110,"type":95,"citation":111},"24141976","Gullo FP, Rossi SA, Sardi Jde C, Teodoro VL, Mendes-Giannini MJ, Fusco-Almeida AM. Cryptococcosis: epidemiology, fungal resistance, and new alternatives for treatment. Eur J Clin Microbiol Infect Dis. 2013 Nov;32(11):1377-91. doi: 10.1007\u002Fs10096-013-1915-8. Epub 2013 Jul 4.",{"pmid":113,"type":95,"citation":114},"18449582","Baddley JW, Perfect JR, Oster RA, Larsen RA, Pankey GA, Henderson H, Haas DW, Kauffman CA, Patel R, Zaas AK, Pappas PG. Pulmonary cryptococcosis in patients without HIV infection: factors associated with disseminated disease. Eur J Clin Microbiol Infect Dis. 2008 Oct;27(10):937-43. doi: 10.1007\u002Fs10096-008-0529-z. Epub 2008 May 1.",{"pmid":116,"type":95,"citation":117},"23697747","Chen SC, Korman TM, Slavin MA, Marriott D, Byth K, Bak N, Currie BJ, Hajkowicz K, Heath CH, Kidd S, McBride WJ, Meyer W, Murray R, Playford EG, Sorrell TC; Australia and New Zealand Mycoses Interest Group (ANZMIG) Cryptococcus Study. Antifungal therapy and management of complications of cryptococcosis due to Cryptococcus gattii. Clin Infect Dis. 2013 Aug;57(4):543-51. doi: 10.1093\u002Fcid\u002Fcit341. Epub 2013 May 22.",{"pmid":119,"type":95,"citation":120},"23874010","Pappas PG. Cryptococcal infections in non-HIV-infected patients. Trans Am Clin Climatol Assoc. 2013;124:61-79.",{"pmid":122,"type":95,"citation":123},"17710620","Meletiadis J, Walsh TJ, Choi EH, Pappas PG, Ennis D, Douglas J, Pankey GA, Larsen RA, Hamill RJ, Chanock S. Study of common functional genetic polymorphisms of FCGR2A, 3A and 3B genes and the risk for cryptococcosis in HIV-uninfected patients. Med Mycol. 2007 Sep;45(6):513-8. doi: 10.1080\u002F13693780701390140.",{"pmid":125,"type":95,"citation":126},"7935577","Schepelmann K, Muller F, Dichgans J. Cryptococcal meningitis with severe visual and hearing loss and radiculopathy in a patient without immunodeficiency. Mycoses. 1993 Nov-Dec;36(11-12):429-32. doi: 10.1111\u002Fj.1439-0507.1993.tb00734.x.",{"pmid":128,"type":95,"citation":129},"23509356","Rosen LB, Freeman AF, Yang LM, Jutivorakool K, Olivier KN, Angkasekwinai N, Suputtamongkol Y, Bennett JE, Pyrgos V, Williamson PR, Ding L, Holland SM, Browne SK. Anti-GM-CSF autoantibodies in patients with cryptococcal meningitis. J Immunol. 2013 Apr 15;190(8):3959-66. doi: 10.4049\u002Fjimmunol.1202526. Epub 2013 Mar 18.",{"pmid":131,"type":95,"citation":132},"24196381","Rabbani B, Tekin M, Mahdieh N. The promise of whole-exome sequencing in medical genetics. J Hum Genet. 2014 Jan;59(1):5-15. doi: 10.1038\u002Fjhg.2013.114. Epub 2013 Nov 7.",{"pmid":134,"type":95,"citation":135},"20858594","Mullaney JM, Mills RE, Pittard WS, Devine SE. Small insertions and deletions (INDELs) in human genomes. Hum Mol Genet. 2010 Oct 15;19(R2):R131-6. doi: 10.1093\u002Fhmg\u002Fddq400. Epub 2010 Sep 21.",{"pmid":137,"type":95,"citation":138},"18462102","De Pauw B, Walsh TJ, Donnelly JP, Stevens DA, Edwards JE, Calandra T, Pappas PG, Maertens J, Lortholary O, Kauffman CA, Denning DW, Patterson TF, Maschmeyer G, Bille J, Dismukes WE, Herbrecht R, Hope WW, Kibbler CC, Kullberg BJ, Marr KA, Munoz P, Odds FC, Perfect JR, Restrepo A, Ruhnke M, Segal BH, Sobel JD, Sorrell TC, Viscoli C, Wingard JR, Zaoutis T, Bennett JE; European Organization for Research and Treatment of Cancer\u002FInvasive Fungal Infections Cooperative Group; National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\u002FMSG) Consensus Group. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer\u002FInvasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC\u002FMSG) Consensus Group. Clin Infect Dis. 2008 Jun 15;46(12):1813-21. doi: 10.1086\u002F588660.",[140],{"label":141,"url":142},"NIH Clinical Center Detailed Web Page","https:\u002F\u002Fclinicalstudies.info.nih.gov\u002Fcgi\u002Fdetail.cgi?A_1993-I-0106.html",{"nct_id":4,"conditions":144,"biomarkers":146},[18,21,19,22,145],"Cryptococcus gattii infection",[147],"Cryptococcal Antigen",{"nct_id":4,"found":48,"summary":149,"prompt_version":159},{"design":150,"status":151,"heading":152,"summary":153,"follow_up":154,"word_count":155,"commitments":156,"compensation":157,"drugs_mentioned":158},"This is an observational study, meaning researchers will watch and learn from participants without giving them specific treatments. It plans to include 800 participants.","completed","Observational Study on Fungal Infection Susceptibility (Cryptococcosis)","This observational study is looking into why some healthy adults get cryptococcosis, a fungal infection, even without known immune problems. Researchers want to understand the full range of how this infection affects people and what might make them more likely to get it. You could join if you are an adult (18-99 years old) who has cryptococcosis, confirmed by tests like tissue samples, cultures, or a positive antigen test. The study aims to characterize the clinical disease over 1 to 5 years. There are no specific interventions or drugs being tested in this study; it's about observing and understanding the condition. The study is currently unclear on its status and plans to enroll 800 participants.","The study aims to characterize the clinical disease of cryptococcosis over 1 to 5 years.",115,"You would undergo various sample collections, including saliva, blood, eyebrow hair, spinal fluid (CSF), and nail clippings. You will receive standard medical care for your condition.","Not stated in the trial record.",[],"v2"]