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Trial record 10 of 24 for:    "Hyperthyroidism" | "Anti-Inflammatory Agents"

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

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ClinicalTrials.gov Identifier: NCT03098225
Recruitment Status : Not yet recruiting
First Posted : March 31, 2017
Last Update Posted : April 17, 2019
Sponsor:
Information provided by (Responsible Party):
Marinò Michele, University of Pisa

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.


Condition or disease Intervention/treatment Phase
Thyroid Associated Ophthalmopathy Radiation: Orbital radiotherapy Drug: Methylprednisolone Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Masking Description: Ophthalmology blinded to treatment
Primary Purpose: Treatment
Official 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
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : March 31, 2023
Estimated Study Completion Date : March 31, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Steroids

Arm Intervention/treatment
Experimental: Radiotherapy
Patients with moderately severe GO treated with Intravenous glucocorticoids associated with orbital radiotherapy
Radiation: Orbital radiotherapy
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 Name: OR

Drug: Methylprednisolone
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 Name: ivGC

Active Comparator: No Radiotherapy
Patients with moderately severe GO treated with Intravenous glucocorticoids alone
Drug: Methylprednisolone
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 Name: ivGC




Primary Outcome Measures :
  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 Outcome Measures :
  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)



Information from the National Library of Medicine

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Ages Eligible for Study:   35 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. No major treatments for hyperthyroidism (thyroidectomy or radioiodine) in the last 3 months
  3. Euthyroidism on anti-thyroid medications or L'thyroxine (LT4) since at least 2 months
  4. GO symptoms lasting since no more than one year
  5. Active GO: CAS ≥ 3 out of 7 (worst eye)
  6. 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
  7. No corticosteroids or immunosuppressive treatment for GO in the last 3 months
  8. No contraindication to OR: diabetes, hypertension, retinopathy of any type, glaucoma
  9. Male and female patients of age: 35-75 years
  10. Effective method of contraception during the whole trial and at least six weeks after last intake of trial drugs (only female of reproducing age)
  11. No mental illness that prevent patients from comprehensive, written informed consent
  12. Compliant patient, regular follow-up possible

Exclusion Criteria:

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03098225


Contacts
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Contact: Michele Marinò, MD +39-348-0616959 michele.marino@med.unipi.it
Contact: Marenza Leo, MD +39-389-7993873 marenzaleo@libero.it

Sponsors and Collaborators
University of Pisa

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Responsible Party: Marinò Michele, Ricercatore (Assistant Professor), University of Pisa
ClinicalTrials.gov Identifier: NCT03098225     History of Changes
Other Study ID Numbers: ORGO
First Posted: March 31, 2017    Key Record Dates
Last Update Posted: April 17, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Hyperthyroidism
Anti-Inflammatory Agents
Graves Ophthalmopathy
Eye Diseases
Eye Diseases, Hereditary
Graves Disease
Exophthalmos
Orbital Diseases
Genetic Diseases, Inborn
Goiter
Thyroid Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Glucocorticoids
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents