[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100314156":3},{"organization":4,"armGroups":7,"interventions":31,"overallOfficials":41,"centralContacts":45,"locations":54,"responsibleParty":121,"collaborators":123,"id":128,"slug":129,"hasResults":130,"nctId":131,"briefTitle":132,"officialTitle":133,"acronym":134,"eligibilityCriteria":135,"healthyVolunteers":130,"sex":136,"minAge":10,"maxAge":137,"enrollmentInfo":138,"targetDuration":10,"studyType":141,"phases":10,"briefSummary":142,"conditions":143,"keywords":145,"overallStatus":91,"whyStopped":10,"lastUpdateSubmitDate":154,"lastUpdatePostDateStruct":155,"startDateStruct":158,"completionDateStruct":160,"leadSponsor":162,"locationsCount":163},{"fullName":5,"class":6},"University of Exeter","OTHER",[8,15,19,23,27],{"label":9,"type":10,"description":11,"interventionNames":12},"Study 1: Existing EET1D (Case)",null,"* Aged 0 to 70 years\n* Clinical diagnosis of diabetes \\\u003C24 months (+ evidence of WHO diabetes criteria)\n* Negative genetic test for mutations causing non-autoimmune neonatal diabetes if diagnosed \\\u003C12 months\n* Type 1 diabetes genetic risk score \\>50th centile of T1D reference group, or monogenic cause of T1D (e.g. STAT3 or FOXP3 mutation).",[13,14],"Diagnostic Test: Beta Cell Loss and Immune Function","Other: Immune Function with RNAseq",{"label":16,"type":10,"description":17,"interventionNames":18},"Study 1: T1D (Control)","* Age 0-70 years (matched to above)\n* Clinical diagnosis of T1D (diagnosed age 1-20 years)\n* Insulin treated from diagnosis.",[13,14],{"label":20,"type":10,"description":21,"interventionNames":22},"Study 2: Newly diagnosed EET1D (Case)","* Aged 0 to 24 months at recruitment\n* Clinical diagnosis of diabetes \\\u003C24 months (+ evidence of WHO diabetes criteria)\n* Negative genetic test for mutations causing non-autoimmune neonatal diabetes\n* Type 1 diabetes genetic risk score \\>50th centile of T1D reference group, or monogenic cause of T1D (e.g. STAT3 or FOXP3 mutation)",[13,14],{"label":24,"type":10,"description":25,"interventionNames":26},"Monogenic \u002F NDM (Control)","* Diagnosis of diabetes \\\u003C24 months\n* Age 0 to 24 months at recruitment\n* Diagnosis of Monogenic \u002F NDM (confirmed by Exeter Molecular Genetics Laboratory).",[13,14],{"label":28,"type":10,"description":29,"interventionNames":30},"Without diabetes (Control)","* Aged 0-6 years\n* Attending specified participating hospital sites for elective surgery, including but not limited to: inguinal hernia repair, umbilical\u002Fmidline hernia repair, orchidopexy, gastrostomy insertion\u002Fchange, hypospadias repair, cleft palate repair, excision of accessory digit, laryngoscopy, adenoidectomy, tonsillectomy, MRI under general anaesthesia, eye surgery.\n\nShould recruitment be slower than anticipated, we would recruit children with congenital non-immune thyroid disease when they attend paediatric clinic for blood draw.",[13,14],[32,37],{"type":33,"name":34,"description":35,"armGroupLabels":36,"otherNames":10},"DIAGNOSTIC_TEST","Beta Cell Loss and Immune Function","Beta cell loss (measured by serum\u002Furine C-peptide), islet-specific autoantibodies, T1D risk genes and autoreactive CD8 T cells.",[24,9,16,20,28],{"type":6,"name":38,"description":39,"armGroupLabels":40,"otherNames":10},"Immune Function with RNAseq","Immune function (measuring autoantibodies, autoreactive CD8 T cells and RNAseq of immune genes).",[24,9,16,20,28],[42],{"name":43,"affiliation":5,"role":44},"Richard Oram","PRINCIPAL_INVESTIGATOR",[46,50],{"name":43,"role":47,"phone":48,"phoneExt":10,"email":49},"CONTACT","+44 (0) 1392 408538","r.oram@exeter.ac.uk",{"name":51,"role":47,"phone":52,"phoneExt":10,"email":53},"Michelle Hudson","+44 (0) 1392 408181","m.hudson@exeter.ac.uk",[55,74,89,111],{"facility":56,"status":57,"city":58,"state":59,"zip":60,"country":61,"countryCode":62,"cosmosGeoPoint":63,"geoPoint":68,"contacts":69},"Benaroya Research Institute","NOT_YET_RECRUITING","Seattle","Washington","98101-2795","United States","US",{"type":64,"coordinates":65},"Point",[66,67],-122.33207,47.60621,{"lat":67,"lon":66},[70],{"name":71,"role":47,"phone":72,"phoneExt":10,"email":73},"Cate Speake","+1 206 342 6500","cspeake@benaroyaresearch.org",{"facility":75,"status":57,"city":76,"state":76,"zip":77,"country":78,"countryCode":79,"cosmosGeoPoint":80,"geoPoint":84,"contacts":85},"Leiden University Medical Center","Leiden","2333 ZA","Netherlands","NL",{"type":64,"coordinates":81},[82,83],4.49306,52.15833,{"lat":83,"lon":82},[86],{"name":87,"role":47,"phone":10,"phoneExt":10,"email":88},"Bart Roep","b.o.roep@lumc.nl",{"facility":90,"status":91,"city":92,"state":93,"zip":94,"country":95,"countryCode":96,"cosmosGeoPoint":97,"geoPoint":101,"contacts":102},"Royal Devon & Exeter NHS Foundation Trust","RECRUITING","Exeter","Devon","EX2 5DW","United Kingdom","UK",{"type":64,"coordinates":98},[99,100],-3.52751,50.7236,{"lat":100,"lon":99},[103,104,106,109],{"name":43,"role":47,"phone":48,"phoneExt":10,"email":49},{"name":51,"role":47,"phone":105,"phoneExt":10,"email":53},"+44 (0) 1392 408183",{"name":107,"role":108,"phone":10,"phoneExt":10,"email":10},"Andrew T Hattersley","SUB_INVESTIGATOR",{"name":110,"role":108,"phone":10,"phoneExt":10,"email":10},"Timothy McDonald",{"facility":112,"status":113,"city":114,"state":10,"zip":115,"country":95,"countryCode":96,"cosmosGeoPoint":116,"geoPoint":120,"contacts":10},"King's College London","ACTIVE_NOT_RECRUITING","London","SE1 9RT",{"type":64,"coordinates":117},[118,119],-0.12574,51.50853,{"lat":119,"lon":118},{"type":122,"investigatorFullName":10,"investigatorTitle":10,"investigatorAffiliation":10,"oldNameTitle":10,"oldOrganization":10},"SPONSOR",[124,126,127],{"name":125,"class":6},"Royal Devon and Exeter NHS Foundation Trust",{"name":112,"class":6},{"name":56,"class":6},"100314156","extremely-early-onset-type-1-diabetes-extremely-early-onset-type-1-diabetes-a-musketeers-memorandum-study-100314156",false,"NCT03369821","EXtremely Early-onset Type 1 Diabetes EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)","Understanding Beta-cell Destruction Through the Study of EXtremely Early-onset Type 1 Diabetes (A Musketeers' Memorandum Study)","EXE-T1D","Inclusion Criteria:\n\nStudy 1:\n\nEET1D\n\n* Aged 0 to 70 years\n* Clinical diagnosis of diabetes \\\u003C24 months (+ evidence of WHO diabetes criteria)\n* Negative genetic test for mutations causing non-autoimmune neonatal diabetes if diagnosed \\\u003C12 months\n* Type 1 diabetes genetic risk score \\>50th centile of T1D reference group, or monogenic cause of T1D.\n\nT1D Controls\n\n* Age 0-70 years (matched to above)\n* Clinical diagnosis of T1D (diagnosed age 1-20 years)\n* Insulin treated from diagnosis.\n\nMonogenic \u002F NDM controls\n\n* Diagnosis of diabetes \\\u003C12 months\n* Diagnosis of monogenic \u002F NDM (confirmed by Exeter Molecular Genetics Laboratory).\n\nStudy 2:\n\nEET1D\n\n* Aged 0 to 24 months at recruitment\n* Clinical diagnosis of diabetes \\\u003C24 months (+ evidence of WHO diabetes criteria)\n* Negative genetic test for mutations causing non-autoimmune neonatal diabetes\n* Type 1 diabetes genetic risk score \\>50th centile of T1D reference group, or monogenic cause of T1D.\n\nMonogenic\u002FNDM controls\n\n* Diagnosis of diabetes \\\u003C24 months\n* Age 0 to 18 months at recruitment\n* Diagnosis of monogenic\u002FNDM (confirmed by Exeter Molecular Genetics Laboratory).\n\nNon-diabetic controls\n\n* Aged 0-6 years\n* Attending specified participating hospital sites for elective surgery, including but not limited to: inguinal hernia repair, umbilical\u002Fmidline hernia repair, orchidopexy, gastrostomy insertion\u002Fchange, hypospadias repair, cleft palate repair, excision of accessory digit, laryngoscopy, adenoidectomy, tonsillectomy, MRI under general anaesthesia, eye surgery.\n\nExclusion Criteria:\n\nStudy 1:\n\n* Aged \\>70 years\n* No diagnosis of diabetes\n* MODY (e.g. caused by HNF1A\u002FHNF4A\u002FHNF1B\u002FGCK mutations), type 2 diabetes or diabetes related to pancreatic insufficiency or syndromic diabetes\n* Intercurrent illness at time of sampling for PBMCs (see below).\n\nStudy 2:\n\n* Aged \\>24 months\n* Clinical diagnosis of diabetes \\>24 months\n* Intercurrent illness at time of sampling for PBMCs or RNA (see below).\n\nNon-diabetic controls:\n\n* Aged \\>6 years\n* Diagnosis of diabetes or other autoimmune condition\n* Known immunological disorder\n* On immunosuppressive medication\n* Ongoing infections\u002Fsepsis\n* Major congenital abnormality or significant systemic illness that may affect the immune system, e.g. metabolic disease, 22q deletion syndrome\n* Recent (within two weeks) febrile illness\n* Renal failure.\n\nFor PBMC and RNA sampling: Exclusion for factors that may alter T cell function and RNAseq\n\nReview the following exclusion criteria carefully at time of appointment as some details may have changed since initial contact:\n\n* Recreational drug use (excluding cannabis use more than 1 week prior to blood sampling) - drug abuse may alter T cell function\n* Alcohol related illness (excessive alcohol consumption may alter T cell function)\n* Renal failure: Creatinine \\>200 (as may alter T cell function)\n* Any other medical condition which, in the opinion of the investigator, would affect the safety of the subject's participation.\n\nFactors that if temporary would lead to rearrangement of study visit but if long duration, may lead to exclusion subject to the CI's discretion:\n\n* Pregnant or lactating (as this may limit blood sampling and affect T cell function)\n* Any infectious illness within the last 2 weeks if it was a febrile illness, or within 2-3 days if it was non-febrile (as this may activate T cells non-specifically)\n* Taking steroids or other immunosuppressive medications (as these may alter T cell function)\n* Received any immunoglobulin treatments or blood products in the last 3 months (as these may alter T cell function).","ALL","70 Years",{"count":139,"type":140},300,"ESTIMATED","OBSERVATIONAL","Type 1 diabetes (T1D) results from destruction of insulin-producing beta cells in the pancreas by the body's own immune system (autoimmunity). It is not fully understood what causes this type of diabetes and why there is variation in age of onset and severity between people who develop the disease. The aim of this work is to study very unusual people who develop T1D extremely young, as babies under 2 years of age (EET1D). The investigators think that, for the condition to have developed that early, they must have an unusual or extreme form of autoimmunity.\n\nStudying people with EET1D will enable us to look at exactly what goes wrong with the immune system because they have one of the most extreme forms of the disease. Much may be learned about the disease from a small number of rare individuals. The investigators aim to confirm that they have autoimmune type 1 diabetes and then try to understand how they have developed diabetes so young by studying their immune system genes, the function of their immune system, and environmental factors (such as maternal genetics) that may play a role in their development of the disease.\n\nPeople with diabetes diagnosed under 12 months are very rare, live all over the world. and are usually referred to Exeter for genetic testing. Individuals will be contacted via their clinician to ask for more information about their diabetes and their family history. Samples will be collected to study whether they still make any of their own insulin and whether they make specific antibodies against their beta cells in the pancreas. Separately, their immune system will be studied in depth using immune cells isolated from a blood sample. These cells will undergo cutting edge techniques by Dr Tim Tree at King's College London, by Professor Bart Roep at Leiden University Medical Center, Netherlands, and Dr Cate Speake, Benaroya Research Institute, Seattle (USA). Some of these tests have never been used in people of young ages around the world, so an aim of this project will be to develop methods that can be used to study people even if they live far away.\n\nAdditional funding extended the study for a further 3 years (Phase 2) to include recruitment of infants without diabetes, aged 0-6 years, as controls to enable assessment of how the abnormalities found in autoimmune and non-autoimmune diabetes compare to normal early life development of the immune system.\n\nAn additional funding award extended the study (Phase 3) until November 2028, to advance the EXE-T1D program into its third phase, building on major discoveries from phases 1 and 2 to identify, validate, and target immune pathways that drive extremely early-onset type 1 diabetes (eeT1D) and are likely relevant to T1D across all ages. eeT1D cases, diagnosed within the first two years of life, represent particularly aggressive onset of beta-cell autoimmunity. They offer a unique lens to uncover mechanisms of immune dysregulation, informed by both polygenic and monogenic causes. The central aim is to move from pathway discovery to demonstration of novel druggable targets with potential to delay or prevent T1D onset across all ages.",[144],"Type1 Diabetes Mellitus",[146,147,148,149,150,151,152,153],"type 1 diabetes","monogenic diabetes","autoimmune diabetes","early-onset autoimmune diabetes","beta cell (β-cell) destruction","type 1 diabetes genetic risk","extremely early-onset Type 1 diabetes","neonatal diabetes","2025-12-12",{"date":156,"type":157},"2025-12-19","ACTUAL",{"date":159,"type":157},"2017-09-19",{"date":161,"type":140},"2028-11-30",{"name":5,"class":6},4]