Thyroid Associated OphthalmopathyPhase 4ORGONCT03098225
A Trial to Evaluate the Efficacy of Orbital Radiotherapy in Graves' Orbitopathy
A Phase 4 study testing Orbital radiotherapy and Methylprednisolone in people with Thyroid Associated Ophthalmopathy, run by University of Pisa.
Trial 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. Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Thyroid Associated Ophthalmopathy
- What is being tested?
- Orbital radiotherapy and Methylprednisolone
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2024to 31 Mar 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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):
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- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
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
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
- Being tested
- Orbital radiotherapy, Methylprednisolone
- Medical subject headings
- Graves Ophthalmopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Orbital radiotherapyRadiation
Also called OR
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 called ivGC
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.
| Study group | Role | What they receive |
|---|---|---|
| Radiotherapy | Experimental | Patients with moderately severe GO treated with Intravenous glucocorticoids associated with orbital radiotherapy Receives: Radiation: Orbital radiotherapy; Drug: Methylprednisolone |
| No Radiotherapy | Active comparator | Patients with moderately severe GO treated with Intravenous glucocorticoids alone Receives: Drug: Methylprednisolone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 52 weeks
Secondary outcomes (4)
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)
Measured: 26 weeks
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Measured: 26 weeks
GO relapse
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)
Measured: 52 weeks
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Measured: 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2017
- Study start1 Jan 2024 (estimated)
- Primary completion31 Mar 2026 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thyroid Associated OphthalmopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pisa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marinò Michele, University of Pisa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03098225
- Sponsor's protocol ID
- ORGO
- Acronym
- ORGO
- Status last verified
- Mar 2023
- First submitted
- 21 Mar 2017
- Last updated
- 15 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03098225
- Acronym / sponsor ID
- ORGO / ORGO
- Conditions
- Thyroid Associated Ophthalmopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of PisaUniversity, hospital or other
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 31 Mar 2026 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 31 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Radiotherapy | Experimental | Radiation: Orbital radiotherapy, Drug: MethylprednisolonePatients with moderately severe GO treated with Intravenous glucocorticoids associated with orbital radiotherapy |
| No Radiotherapy | Active comparator | Drug: MethylprednisolonePatients with moderately severe GO treated with Intravenous glucocorticoids alone |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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)
Key exclusion criteria (14 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Orbital radiotherapyAlso: ORA 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. | Radiation | Radiotherapy |
| MethylprednisoloneAlso: ivGCMethylprednisolone 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. | Drug | No Radiotherapy, Radiotherapy |
Primary outcome
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)
4 secondary outcomes
Comparison of overall GO outcome determined using a composite evaluation
Time frame: 26 weeks
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Time frame: 26 weeks
GO relapse
Time frame: 52 weeks
Comparison of a disease specific quality of life questionnaire (GO-QoL)
Time frame: 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Mar 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Orbital radiotherapy and Methylprednisolone in people with Thyroid Associated Ophthalmopathy, run by University of Pisa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 15 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michele Marinò, MD (+39-348-0616959, michele.marino@med.unipi.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of overall GO outcome determined using a composite evaluation (time frame: 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Mar 2023.