NCT04936854

Sirolimus vs Corticosteroids in Treatment of Thyroid Eye Disease

Prospective Comparison of Sirolimus Against Corticosteroids in Treatment of Patients With Active Thyroid Eye Disease

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Haukeland University Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to determine whether Sirolimus is more effective and burdened with less side effects than conventional treatment with corticosteroids in patients with active thyroid eye disease.

Detailed description

Grave's disease is one of the most common autoimmune diseases. Thyroid eye disease is affecting nearly 50% of patients with Grave's disease. European guidelines recommend treating patients with serious TED in the acute face with intravenous steroids for 12 weeks. This treatment is burdened with metabolic complications, like raised blood pressure, high blood glucose, worsening of diabetes, osteoporosis, and weight gain. In addition, peptic ulcer and psychological disturbances are frequently seen. Long-term treatment with high doses of steroids could also suppress the corticotropic axis for a variable time period, giving temporary iatrogenic adrenal insufficiency. It is paramount to develop a treatment with equal or better effect and fewer complications for this group of patients. Recently, Teprotumumab, which act by inhibiting Insulin-Like Growth Factor-1 (IGF-1), has been introduced in treatment of TED. This represents a new area in the anti-inflammatory treatment of the disease. The anti-inflammatory effect of Sirolimus has not been examined in patients with TED, but there are two promising case-reports describing excellent response. Sirolimus have multiple immunosuppressive actions that may be favourable in the inflammatory response in TED. These are: inhibiting T-cell activation, anti-fibroblast effect and blocking the IGF-1 pathway. In contrast to other immunosuppressive drugs, Sirolimus is associated few side effects at low doses. The investigators are planning a comparative study of conventional treatment (corticosteroids) compared with Sirolimus, regarding clinical outcomes and adverse effects. The investigators plan to include a total of 60 patients (30 in each group) with moderate to severe TED over a period of approximately 3 years.

Conditions

• Thyroid-Associated Ophthalmopathy

Interventions

Type	Name	Description
DRUG	Sirolimus 1 mg Oral Tablet	2 mg Sirolimus (two 1 mg tablets) on the first day, followed by 0,5 mg Sirolimus (half 1 mg tablet) per day for 12 weeks.
DRUG	Methylprednisolone	500 mg Methylprednisolone intravenously once a week for 6 weeks, followed by 250 mg once a week for 6 weeks. Total period of treatment 12 weeks.

Timeline

• Start date: 2023-01-01
• Primary completion: 2028-01-01
• Completion: 2028-12-01
• First posted: 2021-06-23
• Last updated: 2025-09-22

Locations

1 site across 1 country: Norway

Regulatory

• FDA-regulated drug study