[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100613077":3},{"organization":4,"outcomesModule":7,"designInfo":38,"detailedDescription":45,"studyPopulation":37,"armGroups":46,"interventions":56,"overallOfficials":62,"centralContacts":67,"locations":72,"responsibleParty":92,"collaborators":96,"id":99,"slug":37,"hasResults":100,"nctId":101,"briefTitle":102,"officialTitle":103,"acronym":104,"eligibilityCriteria":105,"healthyVolunteers":106,"sex":107,"minAge":108,"maxAge":37,"enrollmentInfo":109,"targetDuration":37,"studyType":112,"phases":113,"briefSummary":115,"conditions":116,"keywords":118,"overallStatus":75,"whyStopped":37,"lastUpdateSubmitDate":122,"lastUpdatePostDateStruct":123,"startDateStruct":126,"completionDateStruct":128,"leadSponsor":130,"locationsCount":131},{"fullName":5,"class":6},"Universitaire Ziekenhuizen KU Leuven","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":20,"otherOutcomes":37},[9,13,16],{"measure":10,"description":11,"timeFrame":12},"Change in STAT phosphorylation levels in peripheral blood mononuclear cells (PBMCs) after cytokine stimulation with and without JAK inhibitor exposure","Quantification via Median fluorescence intensity (MFI) of phosphorylated STAT1, STAT3, and STAT5 using multiparameter flow cytometry in bulk PBMCs and sorted T cells, B cells, NK cells, and monocyte subsets after standardized cytokine stimulation (e.g., IFNα, IFNγ, IL-6, IL-2) with or without JAK inhibitor exposure. Outcomes reported as fold-change relative to baseline.","From time of inclusion to 24 months",{"measure":14,"description":15,"timeFrame":12},"Change in transcriptional profiles of immune cell subsets during JAK inhibitor treatment","Differential gene expression assessed by single-cell RNA sequencing of PBMCs. Outcome is reported as the number of differentially expressed genes (adjusted p\\\u003C0.05) at different sampling timepoints (n=3)",{"measure":17,"description":18,"timeFrame":19},"Impact of ex vivo gene therapeutic correction in STAT1 gain-of-function patient-derived PBMCs","On-target editing efficiency measured as percentage of corrected alleles by targeted sequencing.","24 months from inclusion",[21,24,27,31,34],{"measure":22,"description":23,"timeFrame":12},"Mutation-specific differences in response to JAK inhibitor treatment","Comparison of cytokine-induced phosphorylation (MFI of pSTAT1, pSTAT3, pSTAT5) and transcriptional responses (differential expression and pathway enrichment) between patients harboring distinct STAT1 gain-of-function variants. Outcomes reported as half-inhibitory concentration IC50 and area under the curve AUC in comparison to baseline",{"measure":25,"description":26,"timeFrame":12},"Impact of our gene therapeutic approach on cell viability","Cell viability will be measured with MTT-assay",{"measure":28,"description":29,"timeFrame":30},"Off target events in our ex vivo gene therapeutic approach","Off-target events detected by GUIDE-seq and confirmed by amplicon sequencing.","24 months",{"measure":32,"description":33,"timeFrame":30},"Transcriptional correction of our ex vivo gene therapeutic approach","Transcriptional correction measured by single-cell RNA sequencing (fold-change of interferon pathway gene expression).",{"measure":35,"description":36,"timeFrame":30},"Functional differentiation capacity of gene therapy-corrected cells","Functional differentiation capacity of corrected cells assessed by flow cytometry (percentages of T, B, NK, and monocyte subsets).",null,{"allocation":39,"interventionModel":40,"interventionModelDescription":41,"primaryPurpose":42,"observationalModel":37,"timePerspective":37,"maskingInfo":43},"NON_RANDOMIZED","PARALLEL","This is a parallel assignment study with two arms: (1) patients diagnosed with \\[rare disease\\] who will receive \\[describe treatment\\] and have blood drawn at specific time points, and (2) healthy controls who will undergo matched blood sampling for comparative analysis. Healthy controls will not receive the intervention.","TREATMENT",{"masking":44,"maskingDescription":37,"whoMasked":37},"NONE","The investigators want to study ex vivo the effect of JAK-inhibitors on the transcriptional profile and immune cell landscape in patients with inborn errors of the JAK-STAT pathway and the ex vivo evaluation of the feasibility of a gene therapeutic approach for STAT1 GOF. Following aspects will be compared:\n\n* To study pSTAT, transcriptional profile and cytokine production on bulk and sorted peripheral blood cell populations following stimulation in the presence or absence of different jakinibs\n* To evaluate to what extent jakinibs can normalize the transcriptional in different cell types (or not and identify blind spots of this treatment strategy)\n* To evaluate ex vivo the impact of a gene therapeutic approach for STAT1 GOF.",[47,52],{"label":48,"type":6,"description":49,"interventionNames":50},"Patients with a monogenic IEI with an hyperactive JAK-STAT pathway","Adult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway.",[51],"Diagnostic Test: blood sampling",{"label":53,"type":6,"description":54,"interventionNames":55},"Healthy controls","Healthy controls (without immune-mediated disease)",[51],[57],{"type":58,"name":59,"description":60,"armGroupLabels":61,"otherNames":37},"DIAGNOSTIC_TEST","blood sampling","Blood\u002Fserum samples will be collected during routine clinical visits at the time of planned peripheral venous blood sampling. Samples will be processed and either used immediately (flow cytometry-based cell sorting, gDNA extraction, in vitro functional assays, primary cell culture or single-cell applications) or stored for later analysis.",[53,48],[63],{"name":64,"affiliation":65,"role":66},"Rik Schrijvers, MD, PhD","UZ Leuven","PRINCIPAL_INVESTIGATOR",[68],{"name":64,"role":69,"phone":70,"phoneExt":37,"email":71},"CONTACT","+3216342985","rik.schrijvers@uzleuven.be",[73],{"facility":74,"status":75,"city":76,"state":77,"zip":78,"country":79,"countryCode":80,"cosmosGeoPoint":81,"geoPoint":86,"contacts":87},"University Hospitals Leuven,","RECRUITING","Leuven","Vlaams-Brabant","3000","Belgium","BE",{"type":82,"coordinates":83},"Point",[84,85],4.70093,50.87959,{"lat":85,"lon":84},[88],{"name":89,"role":69,"phone":37,"phoneExt":90,"email":91},"Cecilia Iglesias Herrero, MPharm","+34695118905","cecilia.iglesiasherrero@kuleuven.be",{"type":93,"investigatorFullName":94,"investigatorTitle":95,"investigatorAffiliation":5,"oldNameTitle":37,"oldOrganization":37},"SPONSOR_INVESTIGATOR","prof. dr. Rik Schrijvers","Prof. dr.",[97],{"name":98,"class":6},"Research Foundation - Flanders (Fonds Wetenschappelijk Onderzoek)","100613077",false,"NCT07261891","Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders","Ex Vivo Evaluation of JAK-inhibitor and Gene Therapeutical Approach in JAK-STAT Related Disorders (JAKarta Study)","JAKarta","Inclusion Criteria:\n\n* Cases (A): adult patients presenting with a genetically confirmed or highly suspected disorder leading to an exagerated JAK-STAT pathway.\n* Controls (B): participants eligible for inclusion in this study must fall in one of the following categories:\n* Healthy controls (without immune-mediated disease)\n\nExclusion Criteria:\n\n* Children (\\\u003C 18 years at time of recruitment)\n* Persons unable or unwilling to give informed consent",true,"ALL","18 Years",{"count":110,"type":111},20,"ESTIMATED","INTERVENTIONAL",[114],"NA","The investigators want to study the JAK-inhibitors and their impact on the immune system and evaluate the potential of a gene-therapeutic strategy",[117],"Primary Immunodeficiency Diseases (PID)",[119,120,121],"JAK inhibitors","STAT1 gain-of-function","gene therapy","2025-11-28",{"date":124,"type":125},"2025-12-03","ACTUAL",{"date":127,"type":125},"2024-11-21",{"date":129,"type":111},"2030-12-01",{"name":94,"class":6},1]