[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"cryptococcal-meningitis\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:cryptococcal-meningitis":29},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,43,72,96],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":26,"conditions":27,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":32,"startDateStruct":35,"completionDateStruct":37,"leadSponsor":39,"locationsCount":42},"100567294","phase-2-platform-trial-for-cryptococcal-meningitis-platform-cm-100567294",false,"NCT06666322","Platform Trial For Cryptococcal Meningitis (PLATFORM-CM)","Platform Trial For Cryptococcal Meningitis","PLATFORM-CM","Inclusion Criteria:\n\n* CSF cryptococcal antigen (CrAg) positive meningitis\n* Living with HIV\n* Ability and willingness to provide informed consent\n* Willing to receive protocol-specified lumbar punctures\n* Age \\>= 18 years\n* Female participants of childbearing potential who are participating in sexual activity that could lead to pregnancy must agree to use reliable forms of contraception (duration will be indicated in each Trial Appendix).\n\nExclusion Criteria:\n\n* Received 3 or more doses of antifungal therapy for meningitis within last 30 days\n* Inability to take enteral (oral or nasogastric) medicine\n* Cannot or unlikely to attend regular clinic visits\n* Receiving chemotherapy or corticosteroids\n* Receiving hemodialysis or known liver cirrhosis\n* Suspected Paradoxical immune reconstitution inflammatory syndrome (IRIS)\n* Pregnancy or breastfeeding\n* Previous administration of investigational study drug\n* Any condition for which participation would not be in the best interest of the participant or that could limit protocol specified assessments\n* Trial Appendix study-drug specific eligibility criteria","ALL","18 Years",{"count":20,"type":21},2000,"ESTIMATED","INTERVENTIONAL",[24,25],"PHASE2","PHASE3","Cryptococcal meningitis is a fungal infection that causes a severe syndrome of meningitis that is 100% fatal without antifungal therapy. Even with antifungal therapy, mortality rates remain high, especially in low and middle income countries where the ongoing HIV\u002FAIDS pandemic increases the risk of cryptococcosis among persons living with HIV infection. The combination of amphotericin and flucytosine (5-FC) has been the mainstay of therapy for the initial management of cryptococcal meningitis for 4 decades. Indeed, the effective delivery of these first line therapy in Africa can lower mortality to 25%. However, several challenges exist. First, even while 5-FC is included on the WHO list of essential medicines, the availability of 5-FC worldwide is limited. Second, liposomal amphotericin (Ambisome ®) is currently available from a single source supplier, creating risk. Third, current therapies have substantial toxicity. Lastly, with widespread agricultural fungicide use of azoles, the median fluconazole minimum inhibitory concentration (MIC50 ) for Cryptococcus has doubled since 2013. Globally, new or improved antifungals are needed for cryptococcal meningitis, particularly those which have less toxicity, greater efficacy, a prolonged half-life, and minimal drug-drug interactions. As multiple new antifungal medicines are on the horizon, this platform trial utilizes a master protocol to investigate, multiple regimens using standardized eligibility criteria, standardized study schedule of events, and standardized contemporary endpoints.",[28,29],"Hiv","Cryptococcal Meningitis","RECRUITING","2026-06-17",{"date":33,"type":34},"2026-06-22","ACTUAL",{"date":36,"type":34},"2025-05-28",{"date":38,"type":21},"2032-04-21",{"name":40,"class":41},"University of Minnesota","OTHER",2,{"id":44,"slug":45,"hasResults":11,"nctId":46,"briefTitle":47,"officialTitle":47,"acronym":4,"eligibilityCriteria":48,"healthyVolunteers":49,"sex":17,"minAge":18,"maxAge":4,"enrollmentInfo":50,"targetDuration":4,"studyType":52,"phases":4,"briefSummary":53,"conditions":54,"keywords":57,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":64,"startDateStruct":66,"completionDateStruct":4,"leadSponsor":68,"locationsCount":71},"100122933","etiology-pathogenesis-and-natural-history-of-idiopathic-cd4-lymphocytopenia-100122933","NCT00867269","Etiology, Pathogenesis, and Natural History of Idiopathic CD4+ Lymphocytopenia","* ICL PARTICPANT INCLUSION CRITERIA:\n\nTo be eligible for this study, patients must satisfy all of the following inclusion criteria:\n\n1. Age greater than or equal to 18 years\n2. Absolute CD4 count \\\u003C 300 cells\u002FmicroL or \\\u003C 20% of total T cells on at least two occasions at least 6 weeks apart\n3. Ongoing care by a referring primary care physician\n4. Willingness to allow storage of blood and tissue samples for future analysis\n\nICL PARTICPANT EXCLUSION CRITERIA:\n\nPatients will be ineligible for this study if they satisfy any of the following criteria:\n\n1. Known infection with HIV-1, HIV-2, or human T-cell lymphotropic viruses (HTLV-1 or HTLV-2) as demonstrated by enzyme-linked immunosorbent assay (ELISA) and western blot and\u002For viral load testing\n2. Known underlying immunodeficiency syndrome other than ICL\n3. Evidence of active malignancy\n4. Receipt of medications, herbal substances, or biologic agents known to diminish the CD4+ count within 30 days of when the CD4+ lymphocytopenia was detected\n5. Any condition that in the judgment of the investigators would place the subject at undue risk or compromise the results of the study.\n\nBLOOD RELATIVE INCLUSION CRITERIA:\n\nTo be eligible for study participation as a blood relative, subjects must be greater than or equal to 18 years of age and be a blood relative of an individual who meets or has met the CDC criteria for ICL.\n\nHOUSEHOLD CONTACT INCLUSION CRITERIA:\n\nTo be eligible for study participation as a household contact, subjects must be greater than or equal to18 years of age and live within the same household as an ICL subjects participating in this protocol. Blood relatives who are household contacts are eligible to participate.",true,{"count":51,"type":21},950,"OBSERVATIONAL","Background:\n\n* Idiopathic CD4+ lymphocytopenia (ICL) is a condition in which there is a decreased level of CD4+ lymphocytes (a type of white blood cell), which can lead to opportunistic infections or autoimmune disorders and diseases.\n\nObjectives:\n\n* To characterize the natural history with regard to CD4+ T cell count and onset of infection, malignancy, and autoimmunity.\n* To describe the immunological status of patients affected by ICL while providing the best possible standard therapy to eradicate opportunistic infections.\n* To establish the timeline of CD4 lymphocytopenia, with particular focus on defining subgroups of patients according to the decline, stabilization, or rise of CD4+ T cell counts over time.\n* To characterize the opportunistic infections that occur in ICL patients at microbiologic and molecular levels.\n* To characterize the immunophenotype and possible genetic immunodeficiency causes of ICL.\n* To determine whether measurable immunologic parameters correlate with the development of opportunistic infections or other comorbidities such as lymphoma in patients with ICL.\n* To determine whether there is any association between ICL and autoimmunity.\n* To determine CD4+ T cell turnover, survival, functionality, and cytokine responsiveness in ICL patients.\n\nEligibility:\n\n* Patients 2 years of age and older with an absolute CD4 count less than 300 in children 6 years or older and adults or less than 20% of T cells in children younger than 6 on two occasions at least 6 weeks apart.\n* Patients with negative results of HIV testing by ELISA, Western Blot, and viral load.\n* Patients must not have underlying immunodeficiency conditions, be receiving cytotoxic chemotherapy (anti-cancer drugs that kill cells), or have cancer.\n\nDesign:\n\n* At the initial visit to the National Institutes of Health, the following evaluations will be conducted:\n* Personal and family medical histories.\n* Physical examination, including rheumatology evaluation and other consultations as medically indicated (e.g., dermatology, pulmonology, ophthalmology, imaging studies).\n* Blood samples for analysis of red and white blood cell counts, liver function, immune hormones, and antibody and autoantibody levels, white blood cell growth and function, and DNA.\n* Urinalysis and urine pregnancy testing for female patients of childbearing age.\n* Evaluation and treatment of active infections as medically indicated, including biopsies, buccal swabs, pulmonary function tests, and imaging studies.\n* Follow-up visits will take place approximately every 12 months or more frequently if indicated, and will continue for a minimum of 4 years and a maximum of 10 years.\n* Evaluations at follow-up will include blood samples (i.e., CBC with differential, biochemical profile, HIV testing, etc.) and urinalysis and rheumatology consults.",[55,29,56],"Idiopathic CD4+ Lymphocytopenia","Warts",[58,59,60,61,62,63],"Opportunistic Infection","Immunodeficiency Syndrome","Autoimmune Disease","CD4+ Lymphocytes","Natural History","Idiopathic CD4 Lymphocytopenia",{"date":65,"type":34},"2026-06-18",{"date":67,"type":34},"2009-07-13",{"name":69,"class":70},"National Institute of Allergy and Infectious Diseases (NIAID)","NIH",1,{"id":73,"slug":74,"hasResults":11,"nctId":75,"briefTitle":76,"officialTitle":77,"acronym":4,"eligibilityCriteria":78,"healthyVolunteers":49,"sex":17,"minAge":18,"maxAge":79,"enrollmentInfo":80,"targetDuration":4,"studyType":52,"phases":4,"briefSummary":82,"conditions":83,"keywords":88,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":31,"lastUpdatePostDateStruct":92,"startDateStruct":93,"completionDateStruct":4,"leadSponsor":95,"locationsCount":71},"100054401","fungal-infection-susceptibility-100054401","NCT00001352","Fungal Infection Susceptibility","Cryptococcosis in Previously Healthy Adults","* 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.","99 Years",{"count":81,"type":21},800,"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...",[84,85,86,29,87],"Cryptococcal Infection","Cryptococcal Pneumonia","Pulmonary Cryptococcosis","Cryptococcosis",[62,89,90,91],"Cryptococcus","Cryptococcus Neoformans","Cryptococcus gattii",{"date":65,"type":34},{"date":94,"type":34},"1993-04-01",{"name":69,"class":70},{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":101,"acronym":102,"eligibilityCriteria":103,"healthyVolunteers":11,"sex":17,"minAge":104,"maxAge":4,"enrollmentInfo":105,"targetDuration":4,"studyType":22,"phases":107,"briefSummary":108,"conditions":109,"keywords":4,"overallStatus":30,"whyStopped":4,"lastUpdateSubmitDate":110,"lastUpdatePostDateStruct":111,"startDateStruct":113,"completionDateStruct":115,"leadSponsor":117,"locationsCount":71},"100358314","phase-2-single-dose-liposomal-amphotericin-for-asymptomatic-cryptococcal-antigenemia-100358314","NCT03945448","Single Dose Liposomal Amphotericin for Asymptomatic Cryptococcal Antigenemia","Evaluation of CrAg Screening With Enhanced Antifungal Therapy for Asymptomatic CrAg+ Persons","ACACIA","Inclusion Criteria:\n\n* HIV-1 infection\n* Age \\> or equal to15 years\n* Ability and willingness to give informed consent.\n* Plasma\u002FSerum cryptococcal antigen (CRAG)+ with a titer 1:160 or greater\n\nExclusion Criteria:\n\n* Cannot or unlikely to attend regular clinic visits\n* History of cryptococcal infection\n* Symptomatic meningitis (confirmed by CSF CRAG+)\n* \\>14 days of fluconazole therapy\n* Pregnancy (confirmed by urinary or serum pregnancy test)\n* Current breastfeeding\n* Known allergy to amphotericin","15 Years",{"count":106,"type":21},356,[24,25],"This will be a randomized controlled trial of asymptomatic (Cryptococcal Antigen test)CrAg positive persons in Uganda.\n\nPatients will be randomized to receive preemptive treatment with 1 dose of liposomal amphotericin (10mg\u002Fkg) in addition to standard of care fluconazole therapy.\n\nHow the enhanced antifungal therapy prevents progression to meningitis in the first 24-weeks and overall survival in those who receive the intervention compared with participants receiving fluconazole per World Health Organisation (WHO) and national standard of care therapy will be evaluated.",[29],"2026-04-27",{"date":112,"type":34},"2026-04-28",{"date":114,"type":34},"2019-06-20",{"date":116,"type":21},"2027-08",{"name":118,"class":41},"Makerere University"]