[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100655448":3},{"organization":4,"outcomesModule":7,"designInfo":72,"detailedDescription":75,"studyPopulation":76,"armGroups":77,"interventions":92,"overallOfficials":111,"centralContacts":121,"locations":131,"responsibleParty":157,"collaborators":160,"id":166,"slug":167,"hasResults":168,"nctId":169,"briefTitle":170,"officialTitle":171,"acronym":172,"eligibilityCriteria":173,"healthyVolunteers":174,"sex":175,"minAge":176,"maxAge":71,"enrollmentInfo":177,"targetDuration":71,"studyType":180,"phases":71,"briefSummary":181,"conditions":182,"keywords":186,"overallStatus":193,"whyStopped":71,"lastUpdateSubmitDate":194,"lastUpdatePostDateStruct":195,"startDateStruct":198,"completionDateStruct":200,"leadSponsor":202,"locationsCount":203},{"fullName":5,"class":6},"University of Copenhagen","OTHER",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":71},[9],{"measure":10,"description":11,"timeFrame":12},"Incidence of Thyroid Eye Disease (TED) within 12 months","Proportion of participants with newly diagnosed Graves' Disease (GD) who develop TED of any grade during the 12-month follow-up period. TED status is determined by standardized clinical and ophthalmological assessments using the established European Group on Graves' Orbitopathy (EUGOGO) criteria. Reported as a percentage (%) of participants.","Baseline to 12 months",[14,18,21,24,27,30,33,36,39,42,45,48,52,55,59,62,65,68],{"measure":15,"description":16,"timeFrame":17},"Prevalence of TED at baseline assessment","Percentage of participants with newly diagnosed GD who present with TED of any severity at the initial baseline assessment. TED status is determined by standardized clinical and ophthalmological assessments using the established EUGOGO criteria. Reported as a percentage (%) of participants.","Baseline",{"measure":19,"description":20,"timeFrame":12},"Area Under the Receiver Operating Characteristic curve (AUROC) of the multivariable TED prediction model","The AUROC and Harrell's C's Index will be used to evaluate the discriminatory performance of a multivariable model to predict TED within 12 months. These baseline predictors include: 1) Demographics\u002Fclinical findings: age (years), sex, symptom duration (months), smoking status (categorized as current, former, or never-smoker, including tobacco type and habits), and BMI (calculated as weight in kilograms divided by height in meters squared \\[kg\u002Fm²\\]). 2) Thyroid status: TSH, Free T4, T3, TRAb, and functional stimulating\u002Fblocking activity. 3) Standard laboratory panels: biochemistry, hematology, lipids, and liver function markers. 4) Tear-fluid biomarkers and ocular microbiome diversity. The final model performance will be expressed as a probability score on a scale from 0.5 (chance performance) to 1.0 (perfect discrimination).",{"measure":22,"description":23,"timeFrame":12},"Change from baseline in Clinical Activity Score (CAS points)","Change in the CAS between baseline and 12 months. The score ranges from 0 to 7 scale, with higher scores indicating greater inflammatory activity.",{"measure":25,"description":26,"timeFrame":12},"Change from baseline in proptosis","Change in eye protrusion for each eye between baseline and 12 months, measured in milimeter (mm) using Hertel exophthalmometry",{"measure":28,"description":29,"timeFrame":12},"Change from baseline in Gorman Diplopia Score","Change in diplopia from baseline to 12 months, assessed using the Gorman diplopia score. The score ranges from 0 to 3, with higher scores indicating more frequent diplopia.Change in diplopia between baseline and 12 months, assessed using the Gorman diplopia score. The score ranges from 0 to 3, with higher scores indicating more frequent diplopia. Includes evaluation of both pre-existing and new-onset diplopia",{"measure":31,"description":32,"timeFrame":12},"Baseline serum TRAb concentration according to TED status at 12 months","Measurement of baseline total serum TSH receptor antibody (TRAb) concentration using assay-specific units. The concentration will be compared between participants who develop TED and those who remain TED-free at 12 months. Reported in International Units per liter (IU\u002FL).",{"measure":34,"description":35,"timeFrame":12},"Baseline TSH receptor-stimulating antibody activity according to TED status at 12 months","Measurement of baseline TSH receptor-stimulating antibody activity using assay-specific units. The antibody activity will be compared between participants who develop TED within 12 months and those who remain TED-free. Reported as a percentage Specimen-to-Reference Ratio (% SRR) or assay-specific unit.",{"measure":37,"description":38,"timeFrame":12},"Baseline TSH receptor-blocking antibody activity according to TED status at 12 months","Measurement of baseline TSH receptor-blocking antibody activity using assay-specific units. The antibody activity will be compared between participants who develop TED within 12 months and those who remain TED-free. Reported as a percentage inhibition (% inhibition) or assay-specific unit.",{"measure":40,"description":41,"timeFrame":12},"Baseline tear-fluid CCL2 concentration according to TED status at 12 months","Measurement of baseline C-C motif chemokine ligand 2 (CCL2) concentration in tear-fluid samples collected using Schirmer strips. The concentration will be compared between participants who develop TED and those who remain TED-free at 12 months. Reported in picograms per milliliter (pg\u002FmL) or assay-specific normalized units.",{"measure":43,"description":44,"timeFrame":12},"Baseline tear-fluid CD40L concentration according to TED status at 12 months","Measurement of baseline CD40 ligand (CD40L) concentration in tear-fluid samples collected using Schirmer strips. The concentration will be compared between participants who develop TED and those who remain TED-free at 12 months. Reported in picograms per milliliter (pg\u002FmL) or assay-specific normalized units.",{"measure":46,"description":47,"timeFrame":12},"Baseline tear-fluid IL-6 concentration according to TED status at 12 months","Measurement of baseline interleukin-6 (IL-6) concentration in tear-fluid samples collected using Schirmer strips. The concentration will be compared between participants who develop TED and those who remain TED-free at 12 months. Reported in picograms per milliliter (pg\u002FmL) or assay-specific normalized units.",{"measure":49,"description":50,"timeFrame":51},"Ocular surface microbiome diversity according to TED status","Characterization of the ocular surface microbiome diversity derived from conjunctival swab samples using 16S rRNA gene amplicon sequencing. Differences will be evaluated between participants who develop TED and those who remain TED-free. Diversity metrics include:Alpha diversity: Shannon Index (index score), Simpson Index (index score), and Observed Operational Taxonomic Units (OTUs, count).Beta diversity: Bray-Curtis and UniFrac distance matrices (dissimilarity index scores).","12 months",{"measure":53,"description":54,"timeFrame":51},"Relative abundance of specific ocular surface microbial taxa according to TED status","Comparison of the relative abundance of specific bacterial taxa at the phylum, family, and genus levels between participants who develop TED and those who remain TED-free. Results for differentially abundant taxa will be reported as a percentage (%) of total sequences to represent relative abundance, along with their corresponding log2 fold changes.",{"measure":56,"description":57,"timeFrame":58},"Change in Ocular Surface Disease Index score from baseline to 12 months","Change in ocular surface symptoms from baseline to 12 months, assessed using the Ocular Surface Disease Index. The total score ranges from 0 to 100, with higher scores indicating more severe ocular surface symptoms.","Baseline and 12 months",{"measure":60,"description":61,"timeFrame":58},"Change in Graves' Ophthalmopathy Quality of Life (GO-QoL) score from baseline to 12 months","Change in TED related quality of life from baseline to 12 months, assessed using the GO-QoL questionnaire. The questionnaire includes visual functioning and appearance subscales. Each subscale is transformed to a score ranging from 0 to 100, with higher scores indicating better quality of life.",{"measure":63,"description":64,"timeFrame":58},"Change in thyroid-related quality of life composite score using Thyroid-Specific Patient-Reported Outcome (ThyPRO-39) from baseline to 12 months","Change in thyroid-related quality of life (ThyPRO-39) from baseline to 12 months, assessed using the 39-item Thyroid-Specific Patient-Reported Outcome questionnaire. The composite score ranges from 0 to 100, with higher scores indicating a greater impact of thyroid disease and poorer quality of life.",{"measure":66,"description":67,"timeFrame":58},"Change in EQ-5D index value from baseline to 12 months","Change in general health-related quality of life from baseline to 12 months, assessed using the EQ-5D descriptive system and converted to an index value using the prespecified value set.",{"measure":69,"description":70,"timeFrame":58},"Change in EQ Visual Analogue Scale score from baseline to 12 months","Change in participant-reported overall health from baseline to 12 months, assessed using the EQ Visual Analogue Scale. The scale ranges from 0 to 100, with higher scores indicating better self-reported health.",null,{"allocation":71,"interventionModel":71,"interventionModelDescription":71,"primaryPurpose":71,"observationalModel":73,"timePerspective":74,"maskingInfo":71},"COHORT","PROSPECTIVE","Thyroid eye disease (TED), also known as Graves' orbitopathy (GO), is the most common extrathyroidal manifestation of Graves' disease (GD). Its clinical course is heterogeneous, and it remains difficult to predict, at the time of GD diagnosis, which individuals will develop clinically significant eye involvement. Established risk factors, including smoking and elevated levels of TSH receptor antibodies, do not fully explain individual disease progression. Improved early risk stratification is therefore needed to identify participants who may benefit from closer ophthalmological monitoring and timely referral.\n\nThe SOGO study is a prospective observational cohort study conducted in the Capital Region of Denmark. It is designed to include a consecutive cohort of participants with newly diagnosed GD who reside in or receive clinical care within the Capital Region of Denmark. The region has approximately 1.9 million inhabitants, corresponding to approximately one-third of the Danish population. Based on Danish epidemiological data, the annual incidence of GD is estimated at approximately 30.7 cases per 100,000 inhabitants, corresponding to approximately 580 newly diagnosed cases annually in the region.\n\nThe study aims to enrol approximately 350 participants with newly diagnosed GD during the inclusion period from September 1, 2026, to August 31, 2028. Based on the expected number of incident GD cases during the two-year recruitment period, this target is considered feasible. The incidence of TED within the first year after a diagnosis of GD has been reported to be approximately 20% to 30%. The planned cohort size is expected to support exploratory analyses of associations between baseline clinical characteristics, ophthalmological findings, selected biomarkers, ocular surface microbiome characteristics, and the subsequent development of TED.\n\nThe study also includes two comparison groups, each comprising approximately 40 participants. The first is an age- and sex-matched healthy control group. The second comparison group will comprise participants with moderate-to-severe TED. both groups will provide comparative data on ophthalmological findings, biomarker profiles, and ocular surface microbiome characteristics.\n\nThe study is observational and does not involve randomization, experimental treatment, or changes to standard clinical management. However, participants will undergo study-specific research procedures, including standardized ophthalmological assessments, questionnaires, blood sampling, tear-fluid collection, and conjunctival ocular surface swab sampling. Some of these procedures may also be used in routine clinical practice when indicated, but they will be performed in this study according to a standardized research protocol. Diagnosis, treatment, and clinical follow-up of GD and TED will remain the responsibility of each participant's usual treating department.\n\nParticipants with newly diagnosed GD will be followed from baseline to approximately 12 months. Healthy control participants and participants with moderate-to-severe TED will attend one study visit. Study-related assessments will comprise the collection of structured clinical information, patient-reported outcome measures, standardized ophthalmological examinations, and biological samples.\n\nThe clinical assessment will include information on the onset and duration of symptoms, thyroid disease history, smoking status, relevant comorbidities, treatment history, and ocular symptoms. Patient-reported outcome measures (PROMs) will be used to assess ocular symptoms, thyroid-related symptoms, and health-related quality of life.\n\nThe standardized ophthalmological assessment will include visual acuity testing using a Snellen chart, colour vision testing using Ishihara plates, ocular motility assessment, assessment of diplopia, proptosis, optical coherence tomography (OCT), slit-lamp examination, fundoscopy, clinical photography of the eyes and periocular region, Schirmer testing, tear break-up time assessment, and conjunctival ocular surface swab sampling. These examinations will provide standardized research data on ocular surface status, orbital involvement, visual function, and early signs of TED.\n\nBiological samples will include blood, tear fluid, and conjunctival swab samples from the ocular surface. Blood samples will be used for thyroid-related laboratory measurements and biomarker analyses, including analyses of inflammatory, metabolic, and proteomic markers. Tear fluid will be collected using Schirmer strips and analysed for biomarkers reflecting the ocular surface microenvironment. Conjunctival swab samples will be used to characterize the ocular surface microbiome, including microbial composition and diversity. The microbiome analyses are intended solely to characterize microbial material at the ocular surface. No analyses of participants' human DNA or hereditary genetic conditions will be performed.\n\nStudy data will be collected and managed using REDCap. Access to directly identifiable information will be restricted to authorized study personnel. Data will be pseudonymized before analysis, and direct identifiers will be stored and managed separately from the research datasets. Data quality will be supported by standardized data collection procedures, predefined variables, range and consistency checks where appropriate, and systematic review of key variables before statistical analysis.\n\nStatistical analyses will be performed using standard statistical software. Descriptive statistics will be used to summarize baseline characteristics. Continuous variables will be presented as medians with interquartile ranges, while categorical variables will be presented as numbers and percentages. Between-group comparisons will be conducted using appropriate statistical methods. These may include the Mann-Whitney U test for continuous variables and the chi-square test or Fisher's exact test for categorical variables, as appropriate.\n\nAssociations between baseline clinical characteristics, biomarkers, microbiome characteristics, and incident TED will be evaluated using regression-based methods. Multivariable logistic regression will be used to evaluate TED status at approximately 12 months. Time-to-event analyses using Cox proportional hazards models may be conducted if the timing and number of events allow this approach. Analyses will account for relevant clinical covariates, including age, sex, smoking status, body mass index, thyroid biochemistry, and serum TRAb levels.\n\nReceiver operating characteristic analyses may be used to evaluate the discriminatory performance of individual biomarkers or multivariable models. Exploratory biomarker and microbiome analyses will include appropriate measures of microbial diversity, composition, and relative abundance. Statistical planning, modelling, and interpretation of the biomarker and microbiome analyses will be conducted in collaboration with an experienced biostatistician.\n\nThe overall aim of the SOGO study is to generate clinically relevant knowledge that may support the earlier identification of people with newly diagnosed GD who are at increased risk of developing TED. In the longer term, the study may contribute to the development of clinically applicable risk prediction models and more individualized follow-up strategies for people with GD.","Newly diagnosed GD cohort: Potential participants will be identified through approved recruitment reports based on EPIC\u002FSundhedsplatformen and laboratory data. Reports will identify adults referred to endocrinology outpatient clinics in the Capital Region of Denmark with first-time TRAb \\>1.5 IU\u002FL and TSH \\\u003C0.01 mU\u002FL, and no previous TRAb \\>1.5 IU\u002FL. Participants may also be recruited through public announcements.\n\nModerate-to-severe TED group: Participants will be identified among patients followed at the Endocrinology Outpatient Clinic, Herlev Hospital, and approached during a scheduled visit.\n\nHealthy control group: Participants will be recruited through staff advertisements at Herlev and Gentofte Hospital and public announcements.",[78,84,88],{"label":79,"type":71,"description":80,"interventionNames":81},"Newly Diagnosed Graves' Disease Cohort","Adults with newly diagnosed Graves' disease with residence in and\u002For clinical management within the Capital Region of Denmark. Participants will be followed from baseline to approximately 12 months to assess the development of thyroid eye disease and associated clinical, ophthalmological, and biological markers. Standard clinical and ophthalmological evaluations, including fundoscopy, Optical Coherence Tomography (OCT), and Clinical Activity Score (CAS) assessment, are performed at baseline to characterize the cohort.",[82,83],"Other: Study-related ophthalmological assessment and biospecimen collection","Other: Blood biomarkers and standardized blood samples including thyroid function status",{"label":85,"type":71,"description":86,"interventionNames":87},"Healthy Control Group","40 healthy control participants without known Graves' disease or thyroid dysfunction. Participants will undergo one study visit for comparison of ophthalmological findings, biomarker profiles, and ocular surface microbiome characteristics.",[82],{"label":89,"type":71,"description":90,"interventionNames":91},"Moderate-to-Severe Thyroid Eye Disease Group","40 age- and sex-matched control group consisting of patients with moderate-to-severe thyroid eye disease requiring advanced medical treatment. Participants will undergo one study visit for comparison of ophthalmological findings, biomarker profiles, and ocular surface microbiome characteristics.",[82],[93,105],{"type":6,"name":94,"description":95,"armGroupLabels":96,"otherNames":97},"Study-related ophthalmological assessment and biospecimen collection","Participants are not assigned to any treatment or therapeutic intervention as part of the study. Study-related procedures include standardized ophthalmological assessments, patient-reported outcome measures, blood sampling, tear-fluid collection using Schirmer strips, and conjunctival ocular surface swab sampling for ocular microbiome profiling. Standard clinical care is not altered by study participation.",[85,89,79],[98,99,100,101,102,103,104],"Standardized ophthalmological assessment","Biospecimen collection","Tear-fluid sampling","Ocular surface swab sampling","Patient-reported outcome assessment","Quality of life questionnaires","Ocular symptom questionnaires",{"type":6,"name":106,"description":107,"armGroupLabels":108,"otherNames":109},"Blood biomarkers and standardized blood samples including thyroid function status","No experimental or therapeutic interventions are administered. Participants undergo routine blood sampling (including thyroid function, biochemistry, hematology, lipids, and liver function markers) solely to gather baseline predictors for the TED prediction model",[79],[110],"thyroid function, biochemistry, hematology, lipids, and liver function markers",[112,116,119],{"name":113,"affiliation":114,"role":115},"Floriana Bytyqi, M.D","Herlev Hospital","STUDY_DIRECTOR",{"name":117,"affiliation":114,"role":118},"Birte Nygaard, M.D., Ph.D.","PRINCIPAL_INVESTIGATOR",{"name":120,"affiliation":114,"role":115},"Jens Pedersen, M.D., Ph.D.",[122,127],{"name":123,"role":124,"phone":125,"phoneExt":71,"email":126},"Birte Nygaard, M.D., Ph.D","CONTACT","+4538689527","birte.nygaard@regionh.dk",{"name":128,"role":124,"phone":129,"phoneExt":71,"email":130},"Jens Pedersen, M.D., Ph.D","38688583","jens.pedersen@regionh.dk",[132],{"facility":133,"status":71,"city":134,"state":71,"zip":135,"country":136,"countryCode":137,"cosmosGeoPoint":138,"geoPoint":143,"contacts":144},"Department of Medical Diseases, Endocrinology Unit, Herlev-Gentofte Hospital","Herlev","2730","Denmark","DK",{"type":139,"coordinates":140},"Point",[141,142],12.43998,55.72366,{"lat":142,"lon":141},[145,148,150,151,152,155],{"name":117,"role":124,"phone":146,"phoneExt":71,"email":147},"004538689527","birte.nygaard@region.dk",{"name":120,"role":124,"phone":149,"phoneExt":71,"email":130},"004538688583",{"name":117,"role":118,"phone":71,"phoneExt":71,"email":71},{"name":120,"role":118,"phone":71,"phoneExt":71,"email":71},{"name":153,"role":154,"phone":71,"phoneExt":71,"email":71},"Moug Al-Bakri, M.D., Ph.D.","SUB_INVESTIGATOR",{"name":156,"role":154,"phone":71,"phoneExt":71,"email":71},"Floriana Bytyqi, M.D.",{"type":118,"investigatorFullName":158,"investigatorTitle":159,"investigatorAffiliation":114,"oldNameTitle":71,"oldOrganization":71},"Birte Nygaard","Clinical Associate Professor, Ph.D., Chief Physician",[161,164],{"name":162,"class":163},"Department of Medicine, Endocrine Unit Herlev University Hospital, Herlev, Denmark","UNKNOWN",{"name":165,"class":6},"Rigshospitalet, Denmark","100655448","early-risk-stratification-of-thyroid-eye-disease-in-newly-diagnosed-graves-disease-100655448",false,"NCT07812194","Early Risk Stratification of Thyroid Eye Disease in Newly Diagnosed Graves' Disease","Development of a Risk Prediction Model for Graves' Orbitopathy Using Systematic Ophthalmological Data and Inflammatory Metabolic Biomarkers in Patients With Newly Diagnosed Graves' Disease","SOGO","Inclusion Criteria:\n\nNewly Diagnosed Graves' Disease (GD) Cohort:\n\n* Age 18 years or older\n* Newly diagnosed GD\n* Positive TSH receptor antibodies, defined as TRAb \\>1.5 IU\u002FL\n* Biochemical hyperthyroidism, defined as TSH \\\u003C0.01 mIU\u002FL\n* Residence in and\u002For clinical management within the Capital Region of Denmark, including Hvidovre Hospital, Rigshospitalet, Amager Hospital, Nordsjællands Hospital, Herlev Hospital, and Bispebjerg Hospital.\n* Ability to provide oral and written informed consent\n\nHealthy Control Group:\n\n* Age 18 years or older\n* No known history of GD\n* No previous positive TRAb measurement\n* No known thyroid dysfunction requiring antithyroid drug therapy or thyroid hormone replacement therapy\n* Ability to provide oral and written informed consent\n\nModerate-to-Severe Thyroid Eye Disease (TED) Group:\n\n* Age 18 years or older\n* Diagnosis of moderate-to-severe TED\n* Followed or treated in a relevant specialized clinical setting\n* Ability to provide oral and written informed consent\n\nExclusion Criteria:\n\nNewly Diagnosed GD Cohort:\n\n* Age below 18 years\n* Previous documented TRAb measurement \\>1.5 IU\u002FL prior to the current diagnostic episode\n* Inability to provide informed consent\n* Inability to complete the baseline assessment within the predefined study timeframe\n\nHealthy Control Group:\n\n* Age below 18 years\n* Known Graves' disease or previous positive TRAb measurement\n* Known thyroid dysfunction requiring antithyroid drug therapy or thyroid hormone replacement therapy\n* Inability to provide informed consent\n\nModerate-to-Severe TED Group:\n\n* Age below 18 years\n* Inability to provide informed consent\n* Inability to complete the planned study assessment",true,"ALL","18 Years",{"count":178,"type":179},430,"ESTIMATED","OBSERVATIONAL","The aim of this observational study is to investigate why some people with newly diagnosed Graves' disease (GD) develop thyroid eye disease (TED), also known as Graves' orbitopathy, while others do not.\n\nThe main questions the study aims to answer are:\n\n1. What proportion of participants develop TED within one year of being diagnosed with GD?\n2. Which early clinical signs, ophthalmological findings, blood biomarkers, tear-fluid biomarkers, or ocular surface microbiome characteristics are associated with an increased risk of developing thyroid eye disease?\n\nParticipants with newly diagnosed GD will attend two study visits, one at baseline and one approximately one year later. At each visit, participants will:\n\n* Answer questions about their symptoms and quality of life\n* Undergo a standardized eye examination and have clinical photographs taken of their eyes\n* Provide blood samples, tear-fluid samples, and a small swab sample from the ocular surface\n\nThe study will also include healthy volunteers and participants with moderate-to-severe TED. Participants in these comparison groups will attend one study visit. Researchers will compare findings across the groups to better understand the early clinical and biological changes associated with thyroid eye disease.\n\nThe long-term aim is to improve the early detection and follow-up of people with GD who may be at increased risk of developing TED.",[183,184,185],"Graves' Orbitopathy","Thyroid Eye Disease, TED","Graves' Disease",[187,188,189,190,191,192],"Risk stratification","Quality of Life","Tear Fluid Biomarkers","Early Detection","Prospective Cohort Study","Ocular Surface Microbiome","NOT_YET_RECRUITING","2026-09-03",{"date":196,"type":197},"2026-09-10","ACTUAL",{"date":199,"type":179},"2026-09-01",{"date":201,"type":179},"2029-09-01",{"name":5,"class":6},1]