Early Risk Stratification of Thyroid Eye Disease in Newly Diagnosed Graves' Disease
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18+
SponsorUniversity of Copenhagen
About this trial
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:
1. What proportion of participants develop TED within one year of being diagnosed with GD? 2. 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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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
Disqualifiers
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
Trial population
Newly diagnosed GD cohort: Potential participants will be identified through approved recruitment reports based on EPIC/Sundhedsplatformen 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/L and TSH \<0.01 mU/L, and no previous TRAb \>1.5 IU/L. Participants may also be recruited through public announcements. Moderate-to-severe TED group: Participants will be identified among patients followed at the Endocrinology Outpatient Clinic, Herlev Hospital, and approached during a scheduled visit. Healthy control group: Participants will be recruited through staff advertisements at Herlev and Gentofte Hospital and public announcements.
Trial design
Design model
Cohort
Time perspective
Prospective
Treatments tested in this trial
Study-related ophthalmological assessment and biospecimen collection
Other interventionParticipants 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.
Blood biomarkers and standardized blood samples including thyroid function status
Other interventionNo 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
Treatment groups
430 Participants
are divided into 3 treatment groupsGroup A: Newly Diagnosed Graves' Disease Cohort2 interventions
Group B: Healthy Control Group1 intervention
Group C: Moderate-to-Severe Thyroid Eye Disease Group1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline to 12 monthsSecondary outcomes
1
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.
Time frame
Baseline2
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/clinical 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 \[kg/m²\]). 2) Thyroid status: TSH, Free T4, T3, TRAb, and functional stimulating/blocking 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).
Time frame
Baseline to 12 months3
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.
Time frame
Baseline to 12 months4
Change from baseline in proptosis
Change in eye protrusion for each eye between baseline and 12 months, measured in milimeter (mm) using Hertel exophthalmometry
Time frame
Baseline to 12 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Copenhagen
Lead sponsor
Herlev Hospital
Sponsor institution
Department of Medicine, Endocrine Unit Herlev University Hospital, Herlev, Denmark
Collaborator
Rigshospitalet, Denmark
Collaborator
Source ClinicalTrials.gov
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