Graves OphthalmopathyPhase 4CRISEPTEDNCT02339142
Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
A Phase 4 study testing External beam radiotherapy and intravenous corticosteroids (methylprednisolone) in people with Graves Ophthalmopathy, run by University of British Columbia.
Trial summary
Thyroid eye disease is an autoimmune disorder affecting approximately 50% of individuals with autoimmune thyroid diseases resulting in enlargement of ocular muscles and may lead to congestion of the eyelids and ocular surface, ocular movement restriction and double vision, and optic nerve compression and loss of… Read more about this study
- Who is it for?
- Ages 35 years and older
- Conditions the study is for
- Graves Ophthalmopathy
- What is being tested?
- External beam radiotherapy and intravenous corticosteroids (methylprednisolone)
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- No sites listed yet
- Study dates
- Jan 2015to Dec 2019
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Active TED: Onset less than 6 months AND: Progressive with historic or measured worsening in one or more of VISA parameters in past 2 months: (increasing soft tissue inflammatory changes, development of intermittent or constant diplopia or increased prominence of either eye or lid retraction)
- Moderately severe TED (all of the following criteria must be met):
- V: No optic neuropathy I: Inflammatory score >/= 4/10 S: Intermittent or constant diplopia in any direction except primary gaze AND/OR restriction in ductions to < 30 degrees in any cardinal direction on clinical examination
- -
Who cannot join
- Age < 35 yrs
- Diabetes mellitus
- Previous orbital surgery or radiotherapy for TED
- Corticosteroid or immunotherapy within previous 2 months for TED
- Unable or unwilling to provide informed consent-
Trial locations and contacts
No sites are listed yet.
About this study
Thyroid eye disease is an autoimmune disorder affecting approximately 50% of individuals with autoimmune thyroid diseases resulting in enlargement of ocular muscles and may lead to congestion of the eyelids and ocular surface, ocular movement restriction and double vision, and optic nerve compression and loss of vision.
First line medical therapy is oral or intravenous corticosteroids (CS), which several studies have shown results in reduction of soft tissue congestion, but some studies suggesting that ocular restriction or visual loss may still occur in spite of CS therapy.i
Read more
External beam radiotherapy (XRT) is second line therapy but is controversial, with some studies suggesting benefit in preventing onset of double vision or optic nerve compression while other studies suggest it has no benefit. Most proponents of XRT for TED believe that it is most effective early in the disease evolution. XRT has been shown to be a safe therapy with few side-effects, although retinopathy changes have developed in a small percentage of diabetics and its use is avoided for diabetics.
Combined oral prednisone and XRT has been shown to be more effective in reducing soft tissue inflammation and motility complications than either monotherapy in two different studies.
To date there have been no trials comparing combined XRT and iv CS with iv CS alone for early progressive TED to identify potential benefit in reducing the severity of motility disorders or preventing the onset of dysthyroid optic neuropathy. That is the purpose of this study.
Read the detailed description
- Purpose: To demonstrate that combined Radiotherapy (RT) and intravenous corticosteroid (CS) is more effective than iv CS alone in preventing severe motility disruption (including strabismus and primary diplopia) and new-onset dysthyroid optic neuropathy in early progressive thyroid orbitopathy.
- Hypothesis: Combined RT and iv CS are more effective than iv CS alone in preventing motility problems (reduced field of single binocular vision, reduced ductions, strabismus and worsening diplopia) and in preventing new-onset dysthyroid optic neuropathy in patients with early progressive thyroid orbitopathy.
- Justification: Standard therapy for progressive TED is iv CS, occasionally supplemented with RT if complications develop in spite of appropriate iv CS therapy. A single retrospective study suggested that early combined treatment may prevent more serious visual complications; this would be the first randomized controlled prospective trial to see if this finding is true.
- Objectives: Demonstrate a statistically significant reduced rate of new onset optic neuropathy and double vision in patients with progressive TED with combined therapy versus traditional monotherapy.
- Research Method: Multicentre, institutional based, randomized controlled trial.
- Statistical Analysis:
Subjects: 100 patients with early progressive TED randomized equally into two groups:
- Therapy: iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 weeks + XRT 100 Rads to each orbit x 10 doses
- Control: Same iv MP dose + no XRT
- Conditions
- Graves Ophthalmopathy
- Being tested
- External beam radiotherapy, intravenous corticosteroids (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.
External beam radiotherapyRadiation
100 Rads to each lateral orbit x 10 doses
intravenous corticosteroids (methylprednisolone)Drug
Intravenous methylprednisolone (iv MP) 500 mg weekly x 6 weeks, then iv MP 250 mg x 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Combined radiotherapy and iv corticosteroid | Experimental | Therapy: iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 weeks
+ External beam radiotherapy: 100 Rads to each orbit x 10 doses Receives: Radiation: External beam radiotherapy; Drug: intravenous corticosteroids (methylprednisolone) |
| iv Corticosteroid | Active comparator | iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 week No Radiotherapy administered Receives: Drug: intravenous corticosteroids (methylprednisolone) |
What is being measured
The primary outcome is the main question the study is designed to answer.
New onset dysthyroid optic neuropathy
Measured: 1 year
Progression in ocular motility dysfunction (Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery)
Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery at 1 year following initiation of treatment
Measured: 1 year
Participants escaping trial (Number of participants leaving trial because of onset of optic neuropathy or primary strabismus)
Number of participants leaving trial because of onset of optic neuropathy or primary strabismus
Measured: 1 year
Secondary outcomes (4)
VISA inflammatory scores
Ocular Inflammatory and congestive scores
Measured: 6 months and 1 year
Quality of life scores
Specific Graves orbitopathy quality of life scoring systems: TED QOL and GO QOL
Measured: 6 months and 1 year
Proptosis and eyelid retraction changes
Change in proptosis and upper lid retraction
Measured: 1 year
Supplemental iv corticosteroid requirements
Need for additional intravenous corticosteroids
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jan 2015 (estimated)
- Study startJan 2015
- Primary completionDec 2018 (estimated)
- Study completionDec 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves OphthalmopathyStudies of the same condition, open and under way.
- More trials run by University of British ColumbiaThe sponsor's other registered studies.
- 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of British Columbia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peter Dolman, University of British Columbia
- Investigators
- Peter J Dolman, MD, FRCSC, Principal investigator, University of British Columbia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02339142
- Sponsor's protocol ID
- H14-03166
- Acronym
- CRISEPTED
- Status last verified
- Jan 2015
- First submitted
- 12 Jan 2015
- Last updated
- 15 Jan 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
- ClinicalTrials.gov ID
- NCT02339142
- Acronym / sponsor ID
- CRISEPTED / H14-03166
- Conditions
- Graves Ophthalmopathy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- University of British ColumbiaUniversity, hospital or other
- Study start
- Jan 2015
- Primary completion
- Dec 2018 (estimated)
- Study completion
- Dec 2019 (estimated)
- First posted
- 15 Jan 2015 (estimated)
- 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.
Thyroid eye disease is an autoimmune disorder affecting approximately 50% of individuals with autoimmune thyroid diseases resulting in enlargement of ocular muscles and may lead to congestion of the eyelids and ocular surface, ocular movement restriction and double vision, and optic nerve compression and loss of vision.
First line medical therapy is oral or intravenous corticosteroids (CS), which several studies have shown results in reduction of soft tissue congestion, but some studies suggesting that ocular restriction or visual loss may still occur in spite of CS therapy.i
External beam radiotherapy (XRT) is second line therapy but is controversial, with some studies suggesting benefit in preventing onset of double vision or optic nerve compression while other studies suggest it has no benefit. Most proponents of XRT for TED believe that it is most effective early in the disease evolution. XRT has been shown to be a safe therapy with few side-effects, although retinopathy changes have developed in a small percentage of diabetics and its use is avoided for diabetics.
Combined oral prednisone and XRT has been shown to be more effective in reducing soft tissue inflammation and motility complications than either monotherapy in two different studies.
To date there have been no trials comparing combined XRT and iv CS with iv CS alone for early progressive TED to identify potential benefit in reducing the severity of motility disorders or preventing the onset of dysthyroid optic neuropathy. That is the purpose of this study.
Detailed description
- Purpose: To demonstrate that combined Radiotherapy (RT) and intravenous corticosteroid (CS) is more effective than iv CS alone in preventing severe motility disruption (including strabismus and primary diplopia) and new-onset dysthyroid optic neuropathy in early progressive thyroid orbitopathy.
- Hypothesis: Combined RT and iv CS are more effective than iv CS alone in preventing motility problems (reduced field of single binocular vision, reduced ductions, strabismus and worsening diplopia) and in preventing new-onset dysthyroid optic neuropathy in patients with early progressive thyroid orbitopathy.
- Justification: Standard therapy for progressive TED is iv CS, occasionally supplemented with RT if complications develop in spite of appropriate iv CS therapy. A single retrospective study suggested that early combined treatment may prevent more serious visual complications; this would be the first randomized controlled prospective trial to see if this finding is true.
- Objectives: Demonstrate a statistically significant reduced rate of new onset optic neuropathy and double vision in patients with progressive TED with combined therapy versus traditional monotherapy.
- Research Method: Multicentre, institutional based, randomized controlled trial.
- Statistical Analysis:
Subjects: 100 patients with early progressive TED randomized equally into two groups:
- Therapy: iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 weeks + XRT 100 Rads to each orbit x 10 doses
- Control: Same iv MP dose + no XRT
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Combined radiotherapy and iv corticosteroid | Experimental | Radiation: External beam radiotherapy, Drug: intravenous corticosteroids (methylprednisolone)Therapy: iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 weeks + External beam radiotherapy: 100 Rads to each orbit x 10 doses |
| iv Corticosteroid | Active comparator | Drug: intravenous corticosteroids (methylprednisolone)iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 week No Radiotherapy administered |
Who may qualify
- Ages
- 35 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Active TED: Onset less than 6 months AND: Progressive with historic or measured worsening in one or more of VISA parameters in past 2 months: (increasing soft tissue inflammatory changes, development of intermittent or constant diplopia or increased prominence of either eye or lid retraction)
- Moderately severe TED (all of the following criteria must be met):
- V: No optic neuropathy I: Inflammatory score >/= 4/10 S: Intermittent or constant diplopia in any direction except primary gaze AND/OR restriction in ductions to < 30 degrees in any cardinal direction on clinical examination
- -
Key exclusion criteria (5 listed)
- Age < 35 yrs
- Diabetes mellitus
- Previous orbital surgery or radiotherapy for TED
- Corticosteroid or immunotherapy within previous 2 months for TED
- Unable or unwilling to provide informed consent-
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 |
|---|---|---|
| External beam radiotherapy100 Rads to each lateral orbit x 10 doses | Radiation | Combined radiotherapy and iv corticosteroid |
| intravenous corticosteroids (methylprednisolone)Intravenous methylprednisolone (iv MP) 500 mg weekly x 6 weeks, then iv MP 250 mg x 6 weeks | Drug | Combined radiotherapy and iv corticosteroid, iv Corticosteroid |
Primary outcome
New onset dysthyroid optic neuropathy
Time frame: 1 year
Progression in ocular motility dysfunction (Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery)
Time frame: 1 year
Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery at 1 year following initiation of treatment
Participants escaping trial (Number of participants leaving trial because of onset of optic neuropathy or primary strabismus)
Time frame: 1 year
Number of participants leaving trial because of onset of optic neuropathy or primary strabismus
4 secondary outcomes
VISA inflammatory scores
Time frame: 6 months and 1 year
Quality of life scores
Time frame: 6 months and 1 year
Proptosis and eyelid retraction changes
Time frame: 1 year
Supplemental iv corticosteroid requirements
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jan 2015.
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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. This study is not recruiting at the moment.
Peter J Dolman, MD, FRCSC principal investigator
University of British Columbia
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing External beam radiotherapy and intravenous corticosteroids (methylprednisolone) in people with Graves Ophthalmopathy, run by University of British Columbia.
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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 15 Jan 2015. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter J Dolman, MD, FRCSC (604 306 4482, peterdolman@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
New onset dysthyroid optic neuropathy (time frame: 1 year). The study lists 3 primary outcomes in all. 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 Jan 2015.