Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease (CRISEPTED)
Primary Purpose
Graves Ophthalmopathy
Status
Unknown status
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
External beam radiotherapy
intravenous corticosteroids (methylprednisolone)
Sponsored by
About this trial
This is an interventional prevention trial for Graves Ophthalmopathy
Eligibility Criteria
Inclusion Criteria:
- 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
-
Exclusion Criteria:
- 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-
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Combined radiotherapy and iv corticosteroid
iv Corticosteroid
Arm Description
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 MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 week No Radiotherapy administered
Outcomes
Primary Outcome Measures
New onset dysthyroid optic neuropathy
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
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
Secondary Outcome Measures
VISA inflammatory scores
Ocular Inflammatory and congestive scores
Quality of life scores
Specific Graves orbitopathy quality of life scoring systems: TED QOL and GO QOL
Proptosis and eyelid retraction changes
Change in proptosis and upper lid retraction
Supplemental iv corticosteroid requirements
Need for additional intravenous corticosteroids
Full Information
NCT ID
NCT02339142
First Posted
January 12, 2015
Last Updated
January 14, 2015
Sponsor
University of British Columbia
1. Study Identification
Unique Protocol Identification Number
NCT02339142
Brief Title
Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
Acronym
CRISEPTED
Official Title
Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Unknown status
Study Start Date
January 2015 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2019 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of British Columbia
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Graves Ophthalmopathy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Combined radiotherapy and iv corticosteroid
Arm Type
Experimental
Arm Description
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
Arm Title
iv Corticosteroid
Arm Type
Active Comparator
Arm Description
iv MP 500 mg iv weekly for 6 weeks, then 250 mg iv weekly for 6 week No Radiotherapy administered
Intervention Type
Radiation
Intervention Name(s)
External beam radiotherapy
Intervention Description
100 Rads to each lateral orbit x 10 doses
Intervention Type
Drug
Intervention Name(s)
intravenous corticosteroids (methylprednisolone)
Intervention Description
Intravenous methylprednisolone (iv MP) 500 mg weekly x 6 weeks, then iv MP 250 mg x 6 weeks
Primary Outcome Measure Information:
Title
New onset dysthyroid optic neuropathy
Time Frame
1 year
Title
Progression in ocular motility dysfunction (Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery)
Description
Improvement or worsening in motility scores and ocular restriction, and need for strabismus surgery at 1 year following initiation of treatment
Time Frame
1 year
Title
Participants escaping trial (Number of participants leaving trial because of onset of optic neuropathy or primary strabismus)
Description
Number of participants leaving trial because of onset of optic neuropathy or primary strabismus
Time Frame
1 year
Secondary Outcome Measure Information:
Title
VISA inflammatory scores
Description
Ocular Inflammatory and congestive scores
Time Frame
6 months and 1 year
Title
Quality of life scores
Description
Specific Graves orbitopathy quality of life scoring systems: TED QOL and GO QOL
Time Frame
6 months and 1 year
Title
Proptosis and eyelid retraction changes
Description
Change in proptosis and upper lid retraction
Time Frame
1 year
Title
Supplemental iv corticosteroid requirements
Description
Need for additional intravenous corticosteroids
Time Frame
1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
-
Exclusion Criteria:
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-
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Peter J Dolman, MD, FRCSC
Phone
604 306 4482
Email
peterdolman@hotmail.com
First Name & Middle Initial & Last Name or Official Title & Degree
Wilfredo Yap
Phone
604 875-4346
Ext
2
Email
lemontree604@yahoo.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter J Dolman, MD, FRCSC
Organizational Affiliation
University of British Columbia
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease
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