Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease

Graves Ophthalmopathy Clinical Trial

— CRISEPTED  

Official title:

Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02339142
• Other study ID #: H14-03166
• Status: Not yet recruiting
• Phase: Phase 4
• First received: January 12, 2015
• Last updated: January 14, 2015
• Start date: January 2015
• Est. completion date: December 2019

Study information

• Verified date: January 2015
• Source: University of British Columbia
• Contact: Peter J Dolman, MD, FRCSC
• Phone: 604 306 4482
• Email: peterdolman[@]hotmail.com
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical 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 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.

Description:

1. 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.

2. 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.

3. 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.

4. 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.

5. Research Method: Multicentre, institutional based, randomized controlled trial.

6. Statistical Analysis:

Subjects: 100 patients with early progressive TED randomized equally into two groups:

1. 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

2. Control: Same iv MP dose + no XRT

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2019
• Est. primary completion date: December 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 35 Years and older

Eligibility

Inclusion Criteria:

1. 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)

2. 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:

1. Age < 35 yrs

2. Diabetes mellitus

3. Previous orbital surgery or radiotherapy for TED

4. Corticosteroid or immunotherapy within previous 2 months for TED

5. Unable or unwilling to provide informed consent-

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Eye Diseases
• Graves Ophthalmopathy

Intervention

Radiation:
• External beam radiotherapy
100 Rads to each lateral orbit x 10 doses

Drug:
• intravenous corticosteroids (methylprednisolone)
Intravenous methylprednisolone (iv MP) 500 mg weekly x 6 weeks, then iv MP 250 mg x 6 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of British Columbia

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	New onset dysthyroid optic neuropathy		1 year	No
Primary	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	1 year	No
Primary	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	1 year	No
Secondary	VISA inflammatory scores	Ocular Inflammatory and congestive scores	6 months and 1 year	No
Secondary	Quality of life scores	Specific Graves orbitopathy quality of life scoring systems: TED QOL and GO QOL	6 months and 1 year	No
Secondary	Proptosis and eyelid retraction changes	Change in proptosis and upper lid retraction	1 year	No
Secondary	Supplemental iv corticosteroid requirements	Need for additional intravenous corticosteroids	1 year	No