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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
University of British Columbia
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Graves Ophthalmopathy

Eligibility Criteria

35 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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-

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

    First Posted
    January 12, 2015
    Last Updated
    January 14, 2015
    Sponsor
    University of British Columbia
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    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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