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NCT Number: NCT03098225

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

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.

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Key information

Conditions

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

Age range

35 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: OR

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.

Other names: ivGC

Primary outcomes

  1. Comparison of overall GO outcome determined using a composite evaluation

    Time frame: 52 weeks

    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)

Secondary outcomes

  1. Comparison of overall GO outcome determined using a composite evaluation

    Time frame: 26 weeks

    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)

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

    Time frame: 26 weeks

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

  3. GO relapse

    Time frame: 52 weeks

    GO worsening in comparison with the 26 week evaluation, by a composite GO score:

    Worsening is defined as worsening in two parameters in at least one eye:

    The parameters are:

    • Eyelid swelling (worsening according to EUGOGO Atlas evaluation)
    • Lid aperture in mm (significant worsening: 2 or more mm)
    • Clinical activity score (CAS) (7 items: spontaneous pain, evoked pain, eyelid edema, eyelid redness, conjunctiva redness, caruncle edema, chemosis; significant worsening: at least 2 points)
    • Exophthalmos in mm (significant worsening: 2 or more mm)
    • Eye muscle involvement - diplopia score (Gorman score) (significant worsening: appearance or change in the degree, or worsening of ≥12 degrees in motility)

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

    Time frame: 52 weeks

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

Study contacts

Contact information is provided by the study sponsor or research team.

Marenza Leo, MD

CONTACT

[email protected]

+39-389-7993873

Michele Marinò, MD

CONTACT

[email protected]

+39-348-0616959

Sponsors and collaborators

Lead sponsor

University of Pisa

Other

Registry information

Official study title

A Phase IV, Randomized, Multi-center Clinical Trial to Compare the Efficacy of Orbital Radiotherapy in Association With Intravenous Glucocorticoids vs Intravenous Glucocorticoids Alone for Moderately Severe and Active Graves' Orbitopathy

Acronym: ORGO

Important dates

Study start
2024
Primary completion
2026
Study completion
2027
First posted
Mar 31, 2017
Registry last updated
Mar 15, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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