Combined Radiotherapy and Intravenous Steroids for Early Progressive Thyroid Eye Disease

NCT02339142 | Unknown Phase 4

• 1 other identifier: H14-03166
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Graves Ophthalmopathy

Outcome Measures

Primary Outcomes (3)

• New onset dysthyroid optic neuropathy

  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

  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

  1 year

Secondary Outcomes (4)

• VISA inflammatory scores

  6 months and 1 year

• Quality of life scores

  6 months and 1 year

• Proptosis and eyelid retraction changes

  1 year

• Supplemental iv corticosteroid requirements

  1 year

Study Arms (2)

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

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

Drug: intravenous corticosteroids (methylprednisolone)

Interventions

External beam radiotherapy RADIATION

100 Rads to each lateral orbit x 10 doses

Combined radiotherapy and iv corticosteroid

intravenous corticosteroids (methylprednisolone) DRUG

Intravenous methylprednisolone (iv MP) 500 mg weekly x 6 weeks, then iv MP 250 mg x 6 weeks

Combined radiotherapy and iv corticosteroid; iv Corticosteroid

Eligibility Criteria

• Age: 35 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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-

Sponsors & Collaborators

• University of British Columbia: lead

MeSH Terms

Conditions

Graves Ophthalmopathy

Interventions

Methylprednisolone

Condition Hierarchy (Ancestors)

Eye Diseases, Hereditary; Eye Diseases; Graves Disease; Exophthalmos; Orbital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Goiter; Thyroid Diseases; Endocrine System Diseases; Hyperthyroidism; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Peter J Dolman, MD, FRCSC

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peter J Dolman, MD, FRCSC

CONTACT

604 306 4482; peterdolman@hotmail.com

Wilfredo Yap

CONTACT

604 875-4346; lemontree604@yahoo.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Professor

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: January 15, 2015
• Study Start: January 1, 2015
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2019
• Last Updated: January 15, 2015

Record last verified: 2015-01