Sirolimus in Graves' Orbitopathy

Graves Ophthalmopathy Clinical Trial

— RETROSIRGO  

Official title:

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05345119
• Other study ID #: RETROSIRGO
• Status: Completed
• Start date: January 15, 2020
• Est. completion date: June 15, 2021

Study information

• Verified date: April 2022
• Source: University of Pisa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 15, 2021
• Est. primary completion date: June 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

1. Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form

2. A moderate-to-severe GO, defined as the presence of at least one of the following criteria: an exophthalmos =2 mm compared with normal values for sex and race; presence of inconstant to constant diplopia; a lid retraction =2 mm

3. Active GO: CAS (4) =2 out of 7 points in the most affected eye

4. Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment

5. Male and female patients of age: 18-75 years

Exclusion Criteria:

1. Optic neuropathy

2. Treatment with glucocorticoids or other immunosuppressive medications, and/or selenium, and/or orbital radiotherapy and/or orbital decompressive surgery in the 24 weeks preceding the current treatment

3. Mental illness that prevents patients from comprehensive, written informed consent

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy

Intervention

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

Locations

Country	Name	City	State
Italy	Endocrinologia II	Pisa	PI

Sponsors (1)

Lead Sponsor	Collaborator
University of Pisa

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	GO overall response	Percentage of subjects with at least two of the following compared to baseline: a) Improvement in clinical activity score (CAS) by at least 1 point ; b) Improvement in exophthalmos by at least 2 mm; c) Improvement in lid aperture by at least 2 mm; d) Improvement in eye muscle ductions =8 degrees; e) Improvement of visual acuity by at least 0.2/1, without worsening of any of these parameters in the contralateral eye if applicable.	24 weeks
Secondary	Change in exophthalmos	Percentage of subjects with a reduction greater than or equal to 2 mm compared with the baseline evaluation in the study eye, without worsening in the contralateral eye	24 weeks
Secondary	Change in the clinical activity score (CAS)	Percentage of subjects with a reduction of CAS by at least two points in the study eye, without worsening in the contralateral eye	24 weeks
Secondary	Change in quality of life	Comparison of the quality of life scores between the two groups, determined with a questionnaire specific for GO (GO-QoL)	24 weeks
Secondary	Change in eye ductions	Percentage of subjects with an increase in eye ductions at least 8 degrees	24 weeks
Secondary	Change in eyelid aperture	Percentage of subjects with a reduction greater than or equal to 2 mm	24 weeks
Secondary	Change in diplopia	Percentage with an improvement in diplopia	24 weeks