Sirolimus in Graves' Orbitopathy

NCT05345119 | Completed FDA Drug

• 1 other identifier: RETROSIRGO
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Graves Ophthalmopathy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change in exophthalmos

  24 weeks

• Change in the clinical activity score (CAS)

  24 weeks

• Change in quality of life

  24 weeks

• Change in eye ductions

  24 weeks

• Change in eyelid aperture

  24 weeks

Study Arms (2)

Sirolimus

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

Drug: Sirolimus

Methylprednisolone

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

Drug: Methylprednisolone

Interventions

Sirolimus DRUG

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

Sirolimus

Methylprednisolone DRUG

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

Methylprednisolone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive patients with moderate-to-severe, active Graves' orbitopathy treated with either sirolimus of methyprednisolone as a second-line treatment after a previous course of methyprednisolone, over 18 consecutive months

You may qualify if:

• Patients willing and capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form
• 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
• Active GO: CAS (4) ≥2 out of 7 points in the most affected eye
• Previous GO treatment with glucocorticoids and/or orbital radiotherapy and/or orbital decompressive surgery, performed more than 24 weeks before the current treatment
• Male and female patients of age: 18-75 years

You may not qualify if:

• Optic neuropathy
• 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
• Mental illness that prevents patients from comprehensive, written informed consent

Sponsors & Collaborators

• University of Pisa: lead

Study Sites (1)

Endocrinologia II

Pisa, PI, 56124, Italy

Location

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

Sirolimus; Methylprednisolone

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Endocrinology

Study Record Dates

• First Submitted: April 19, 2022
• First Posted: April 25, 2022
• Study Start: January 15, 2020
• Primary Completion: June 15, 2021
• Study Completion: June 15, 2021
• Last Updated: April 25, 2022

Record last verified: 2022-04

Locations

IT (1)