A Trial to Evaluate the Efficacy of Orbital Radiotherapy in Graves' Orbitopathy

NCT03098225 | Not Yet Recruiting Phase 4

• 1 other identifier: ORGO
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

Graves' orbitopathy (GO) is a disfiguring and disabling disease that profoundly impairs the quality of life of affected patients. High dose intravenous (iv) glucocorticoids (GC) (ivGC) is a well established, widely used treatment for active GO. The use of systemic glucocorticoids takes advantage from their immune suppressive and antiinflammatory actions, resulting in an overall beneficial effect ranging from \~35 to \~60% of patients in various studies. The intravenous route of administration has been shown to be superior to the oral route, both in terms of GO outcome and side effect profile. The combination of ivGC and orbital radiotherapy (OR) is used routinely in patients with moderate-severe, active GO, as a second-line treatment, as also recommended in the recent Guidelines published by the European Thyroid Association/European Group on Graves' Orbitopathy. Thus, the majority of studies have shown that OR increases the response rate to GC. Those studies were performed using oral GC, whereas it is not known whether OR potentiate also the effects of ivGC. The present study is aimed at determining whether OR potentiate the effects of ivGC in the treatment of moderately severe and active GO, in terms of GO outcome and quality of life. A possible extension of the study can be foreseen, aimed at investigating the very long time GO outcome.

Conditions

Thyroid Associated Ophthalmopathy

Outcome Measures

Primary Outcomes (1)

• Comparison of overall GO outcome determined using a composite evaluation

  A composite evaluation of GO was described previously. Improvement is defined as amelioration of two parameters in at least one eye, without deterioration of any parameters in both eyes: Deterioration is defined as worsening in two parameters in at least one eye: All other cases are defined as "no change" The parameters are: * Eyelid swelling (improvement/worsening according to EUGOGO Atlas evaluation) * Lid aperture in mm (significant variation: 2 or more mm) * Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant change: at least 2 points) * Exophthalmos in mm (significant variation 2 or more mm) * Eye muscle involvement - diplopia score (Gorman score) (significant variation: disappearance or change in the degree, or improvement of ≥12 degrees in motility)

  52 weeks

Secondary Outcomes (4)

• Comparison of overall GO outcome determined using a composite evaluation

  26 weeks

• Comparison of a disease specific quality of life questionnaire (GO-QoL)

  26 weeks

• GO relapse

  52 weeks

• Comparison of a disease specific quality of life questionnaire (GO-QoL)

  52 weeks

Study Arms (2)

Radiotherapy

EXPERIMENTAL

Patients with moderately severe GO treated with Intravenous glucocorticoids associated with orbital radiotherapy

Radiation: Orbital radiotherapy; Drug: Methylprednisolone

No Radiotherapy

ACTIVE COMPARATOR

Patients with moderately severe GO treated with Intravenous glucocorticoids alone

Drug: Methylprednisolone

Interventions

Orbital radiotherapy RADIATION

A high-voltage linear accelerator will be used and a cumulative radiation dose of 20 Gy will be delivered to each eye in 10 fractionated doses over a period of 2 weeks. All patients will be treated in both eyes.

Also known as: OR

Radiotherapy

Methylprednisolone DRUG

Methylprednisolone pulse therapy for 12 weeks as follows: 500 mg IV once weekly for 6 weeks, then 250 mg IV once weekly for a further 6 weeks. Cumulative dose 4.5 g.

Also known as: ivGC

No Radiotherapy; Radiotherapy

Eligibility Criteria

• Age: 35 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A diagnosis of Graves' disease based on the presence of hyperthyroidism (either untreated or treated with antithyroid drugs) associated with detectable anti-TSH receptor autoantibodies
• No major treatments for hyperthyroidism (thyroidectomy or radioiodine) in the last 3 months
• Euthyroidism on anti-thyroid medications or L'thyroxine (LT4) since at least 2 months
• GO symptoms lasting since no more than one year
• Active GO: CAS ≥ 3 out of 7 (worst eye)
• Moderate or moderately severe GO: at least one of the following signs (worst eye):
• Exophthalmos ≥ 22 mm
• Eye muscle involvement with mono-ocular ductions in any direction of gaze of less than 30° or evident dismotility
• Diplopia according to Gorman score of grades a-c
• No corticosteroids or immunosuppressive treatment for GO in the last 3 months
• No contraindication to OR: diabetes, hypertension, retinopathy of any type, glaucoma
• Male and female patients of age: 35-75 years
• Effective method of contraception during the whole trial and at least six weeks after last intake of trial drugs (only female of reproducing age)
• No mental illness that prevent patients from comprehensive, written informed consent
• Compliant patient, regular follow-up possible

You may not qualify if:

• Absence of Graves' hyperthyroidism (present or past)
• Thyroidectomy or radioiodine in the last 3 months
• Uncontrolled hyperthyroidism or hypothyroidism
• GO symptoms lasting since more than one year
• CAS \<3 (worst eye)
• Optic neuropathy
• Contraindications to OR (diabetes, retinopathy of any kind)
• Pregnancy, breast-feeding women
• No informed consent
• Acute or chronic liver disease
• Relevant Malignancy
• Chronic renal failure or other diseases of any relevance to prevent steroid treatment 13) Corticosteroids or other immunosuppressive agents within last 3 months
• Recent (≤1 year) history of alcoholism or drug abuse
• Previous orbital disease other than GO, eye injuries or surgery

Sponsors & Collaborators

• University of Pisa: lead

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

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)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Michele Marinò, MD

CONTACT

+39-348-0616959; michele.marino@med.unipi.it

Marenza Leo, MD

CONTACT

+39-389-7993873; marenzaleo@libero.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Ophthalmology blinded to treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ricercatore (Assistant Professor)

Study Record Dates

• First Submitted: March 21, 2017
• First Posted: March 31, 2017
• Study Start: January 1, 2024
• Primary Completion: March 31, 2026
• Study Completion (Estimated): March 31, 2027
• Last Updated: March 15, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share