Development of a Risk Prediction Model for Graves' Orbitopathy Using Systematic Ophthalmological Data and Inflammatory Metabolic Biomarkers in Patients With Newly Diagnosed Graves' Disease
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 430
- 试验地点
- 1
- 主要终点
- Incidence of Thyroid Eye Disease (TED) within 12 months
研究概览
简要总结
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.
The main questions the study aims to answer are:
- What proportion of participants develop TED within one year of being diagnosed with GD?
- 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?
Participants with newly diagnosed GD will attend two study visits, one at baseline and one approximately one year later. At each visit, participants will:
- Answer questions about their symptoms and quality of life
- Undergo a standardized eye examination and have clinical photographs taken of their eyes
- Provide blood samples, tear-fluid samples, and a small swab sample from the ocular surface
The 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.
The 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.
详细描述
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.
The 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.
The 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.
The 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.
The 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Newly Diagnosed Graves' Disease (GD) Cohort:
- •Age 18 years or older
- •Newly diagnosed GD
- •Positive TSH receptor antibodies, defined as TRAb >1.5 IU/L
- •Biochemical hyperthyroidism, defined as TSH <0.01 mIU/L
- •Residence in and/or clinical management within the Capital Region of Denmark, including Hvidovre Hospital, Rigshospitalet, Amager Hospital, Nordsjællands Hospital, Herlev Hospital, and Bispebjerg Hospital.
- •Ability to provide oral and written informed consent
- •Healthy Control Group:
- •Age 18 years or older
- •No known history of GD
- •No previous positive TRAb measurement
- •No known thyroid dysfunction requiring antithyroid drug therapy or thyroid hormone replacement therapy
- •Ability to provide oral and written informed consent
- •Moderate-to-Severe Thyroid Eye Disease (TED) Group:
- •Age 18 years or older
- •Diagnosis of moderate-to-severe TED
- •Followed or treated in a relevant specialized clinical setting
- •Ability to provide oral and written informed consent
排除标准
- •Newly Diagnosed GD Cohort:
- •Age below 18 years
- •Previous documented TRAb measurement >1.5 IU/L prior to the current diagnostic episode
- •Inability to provide informed consent
- •Inability to complete the baseline assessment within the predefined study timeframe
- •Healthy Control Group:
- •Age below 18 years
- •Known Graves' disease or previous positive TRAb measurement
- •Known thyroid dysfunction requiring antithyroid drug therapy or thyroid hormone replacement therapy
- •Inability to provide informed consent
- •Moderate-to-Severe TED Group:
- •Age below 18 years
- •Inability to provide informed consent
- •Inability to complete the planned study assessment
研究组 & 干预措施
Newly Diagnosed Graves' Disease Cohort
Adults with newly diagnosed Graves' disease with residence in and/or 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.
干预措施: Study-related ophthalmological assessment and biospecimen collection (Other)
Newly Diagnosed Graves' Disease Cohort
Adults with newly diagnosed Graves' disease with residence in and/or 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.
干预措施: Blood biomarkers and standardized blood samples including thyroid function status (Other)
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.
干预措施: Study-related ophthalmological assessment and biospecimen collection (Other)
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.
干预措施: Study-related ophthalmological assessment and biospecimen collection (Other)
结局指标
主要结局
Incidence of Thyroid Eye Disease (TED) within 12 months
时间窗: Baseline to 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.
次要结局
- Prevalence of TED at baseline assessment(Baseline)
- Area Under the Receiver Operating Characteristic curve (AUROC) of the multivariable TED prediction model(Baseline to 12 months)
- Change from baseline in Clinical Activity Score (CAS points)(Baseline to 12 months)
- Change from baseline in proptosis(Baseline to 12 months)
- Change from baseline in Gorman Diplopia Score(Baseline to 12 months)
- Baseline serum TRAb concentration according to TED status at 12 months(Baseline to 12 months)
- Baseline TSH receptor-stimulating antibody activity according to TED status at 12 months(Baseline to 12 months)
- Baseline TSH receptor-blocking antibody activity according to TED status at 12 months(Baseline to 12 months)
- Change in EQ Visual Analogue Scale score from baseline to 12 months(Baseline and 12 months)
- Baseline tear-fluid CCL2 concentration according to TED status at 12 months(Baseline to 12 months)
- Baseline tear-fluid CD40L concentration according to TED status at 12 months(Baseline to 12 months)
- Baseline tear-fluid IL-6 concentration according to TED status at 12 months(Baseline to 12 months)
- Ocular surface microbiome diversity according to TED status(12 months)
- Relative abundance of specific ocular surface microbial taxa according to TED status(12 months)
- Change in Ocular Surface Disease Index score from baseline to 12 months(Baseline and 12 months)
- Change in Graves' Ophthalmopathy Quality of Life (GO-QoL) score from baseline to 12 months(Baseline and 12 months)
- Change in thyroid-related quality of life composite score using Thyroid-Specific Patient-Reported Outcome (ThyPRO-39) from baseline to 12 months(Baseline and 12 months)
- Change in EQ-5D index value from baseline to 12 months(Baseline and 12 months)
研究者
Birte Nygaard
Clinical Associate Professor, Ph.D., Chief Physician
Herlev Hospital