Overview
The goal of this clinical trial is to learn whether statin therapy and vitamin D supplementation can modify disease activity in patients with active thyroid eye disease. The study will also evaluate the safety of these treatments. The main questions it aims to answer are:
- Does statin therapy change disease activity, as measured by changes in the Clinical Activity Score (CAS) and proptosis?
- Does vitamin D supplementation change disease activity in patients with active thyroid eye disease?
- Does combined treatment with statin and vitamin D produce different effects compared with either treatment alone or standard care?
- What adverse events occur during treatment?
Researchers will compare four groups: standard care alone, statin therapy plus standard care, vitamin D supplementation plus standard care, and combined statin and vitamin D therapy plus standard care.
Participants will:
- Be randomly assigned to one of four treatment groups
- Receive the assigned treatment for 24 weeks
- Attend clinic visits for clinical assessments and blood tests at baseline and at 24 weeks
- Be followed through medical record review for up to three years after completion of the intervention
Description
Thyroid eye disease (TED) is an autoimmune inflammatory disorder commonly associated with Graves' disease. The disease typically follows an active inflammatory phase, characterized by orbital inflammation, pain, redness, swelling, and progression of eye protrusion, followed by an inactive fibrotic phase with more permanent structural changes. Early intervention during the active phase is critical to reduce disease severity and prevent long-term functional and cosmetic complications.
Current treatments for active TED primarily focus on immunosuppression, such as systemic corticosteroids or other immunomodulatory therapies. However, these treatments may be associated with significant side effects and variable treatment responses. Therefore, there is an unmet need for adjunctive therapies with favorable safety profiles that may modify disease activity and change outcomes in patients with active TED.
Recent observational studies have suggested that statin use is associated with a lower risk of developing thyroid eye disease and a reduced severity of disease manifestations. These potential benefits appear to be independent of cholesterol-lowering effects and may be related to the anti-inflammatory and immunomodulatory properties of statins. In addition, vitamin D deficiency has been frequently observed in patients with TED, and vitamin D is known to play a role in immune regulation and inflammatory control. Experimental and clinical studies suggest that vitamin D supplementation may modulate autoimmune activity and modify inflammatory responses.
Despite these findings, there is limited prospective clinical trial evidence evaluating the effects of statin therapy and vitamin D supplementation in patients with active TED. This study is designed as a randomized, open-label, 2×2 factorial clinical trial to evaluate the individual and combined effects of statin therapy and vitamin D supplementation on disease activity in patients with active TED.
Eligible participants with active TED will be randomly assigned to one of four groups: standard care alone, standard care plus statin therapy, standard care plus vitamin D supplementation, or standard care plus combined statin and vitamin D therapy. The intervention period will last for 24 weeks. Statin therapy consists of oral atorvastatin 20 mg once daily, and vitamin D supplementation consists of oral vitamin D at a daily dose of 1400 IU.
The primary outcomes of the study include changes in the Clinical Activity Score (CAS), responder rate defined as a ≥2-point change in Clinical Activity Score (CAS), changes in proptosis measured by Hertel exophthalmometry, and changes in thyroid-stimulating immunoglobulin (TSI) levels from baseline to 24 weeks. Secondary outcomes include changes in thyroid function, lipid profiles, blood glucose levels, and the use of thyroid-related medications and systemic corticosteroids during the intervention period.
Safety assessments will be conducted throughout the study by monitoring clinical symptoms, laboratory parameters, and reported adverse events. After completion of the 24-week intervention, participants will return to standard care and will be followed through medical record review for up to three years to observe long-term disease activity outcomes.
This study aims to provide prospective clinical evidence regarding the potential role of statin therapy and vitamin D supplementation as adjunctive treatments for active thyroid eye disease.
Eligibility
Inclusion Criteria:
- Adults aged 20 years or older
- Diagnosis of active thyroid eye disease with a Clinical Activity Score (CAS) of 3 or higher
- Low-density lipoprotein cholesterol (LDL-C) level of 100 mg/dL or higher
Exclusion Criteria:
- Prior orbital radiotherapy or orbital surgery for thyroid eye disease
- Use of statins or high-dose vitamin D supplementation (greater than 400 IU per day) within 3 months prior to enrollment
- Pregnancy
- Severe renal impairment, defined as an estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m²
