NCT05345119

Sirolimus in Graves' Orbitopathy

An Observational, Retrospective, Single-center, Clinical Study to Evaluate the Efficacy of Sirolimus (Rapamycin) in Patients With Graves' Disease and Moderate-to-severe and Active Graves' Orbitopathy (GO)

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 30 (actual)
• Sponsor: University of Pisa · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

Graves' Orbitopathy (GO) is a disabling and disfiguring condition associated with Graves' Disease, due to autoimmunity against antigens expressed by the thyroid and orbital tissues, and resulting in orbital fibroblast proliferation and release of glycosaminoglycans. The current treatments available, especially glucocorticoids, are not effective in all patients. Two cases of patients with GO treated with Sirolimus have been reported with an excellent response to the drug. The rationale for the use of Sirolimus lies in its mechanisms of action. Sirolimus is able to inhibit T-cell activation as well as fibroblast proliferation. In addition, acts indirectly on the Insulin-Like Growth Factor-1 (IGF-1) pathway, and recent clinical trials have shown that a monoclonal antibody against the IGF-1 receptor (Teprotumumab) is effective in patients with GO. Thus, Sirolimus could be used in GO as monotherapy in patients with GO. The aim of the present drug vs standard treatment, observational study is to evaluate the efficacy of Sirolimus as a second-line treatment in patients with moderately severe, active GO.

Detailed description

Study Design: observational Thirty consecutive patients with moderate-to-severe and active GO treated with sirolimus (15 patients) or methylprednisolone (15 patients) observance 18 consecutive months will be compared. Study Timeline Baseline visit - (Time 0) Treatment period (week 1-week 12): daily administration of the trial agent (Sirolimus) or weekly administration of the standard treatment (methylprednisolone) Outcome visit (week 24)

Conditions

• Graves Ophthalmopathy

Interventions

Type	Name	Description
DRUG	Sirolimus	2 mg orally on the first day followed by 0.5 mg per day for 12 weeks
DRUG	Methylprednisolone	500 mg/weekly (6 weeks) intravenously, 250 mg/weekly (6 weeks) (cumulative dose 4.5 g).

Timeline

• Start date: 2020-01-15
• Primary completion: 2021-06-15
• Completion: 2021-06-15
• First posted: 2022-04-25
• Last updated: 2022-04-25

Locations

1 site across 1 country: Italy

Regulatory

• FDA-regulated drug study