Sirolimus in Graves' Orbitopathy

NCT ID: NCT05345119

Last Updated: 2022-04-25

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-01-15
• Study Completion Date: 2021-06-15

Brief 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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Sirolimus

Treatment with sirolimus for 12 weeks, given as a second-line treatment

Sirolimus

Intervention Type: DRUG

2 mg orally on the first day followed by 0.5 mg per day for 12 weeks

Methylprednisolone

Treatment with methylprednisolone for 12 weeks, given as a second-line treatment

Methylprednisolone

Intervention Type: DRUG

500 mg/weekly (6 weeks) intravenously, 250 mg/weekly (6 weeks) (cumulative dose 4.5 g).

Interventions

Sirolimus

2 mg orally on the first day followed by 0.5 mg per day for 12 weeks

Intervention Type: DRUG

Methylprednisolone

500 mg/weekly (6 weeks) intravenously, 250 mg/weekly (6 weeks) (cumulative dose 4.5 g).

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pisa

OTHER

Sponsor Role: lead

Responsible Party

Marinò Michele

Associate Professor of Endocrinology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Endocrinologia II

Pisa, PI, Italy

Countries

Italy

Other Identifiers

RETROSIRGO

Identifier Type: -

Identifier Source: org_study_id