Status:
COMPLETED
Thyroid Treatment Trial
Lead Sponsor:
Singapore National Eye Centre
Collaborating Sponsors:
International Stem Cell Forum
Conditions:
Graves Ophthalmopathy
Eligibility:
All Genders
21-60 years
Phase:
NA
Brief Summary
This project will compare the efficacy and safety of 2 methods of disease modification in the treatment of active moderate and severe thyroid orbitopathy. A prospective, randomized, double-blind, para...
Detailed Description
Since 1835 when Graves first described the eye changes in thyroid disease, considerable literature on investigating the basic disease process, the clinical behaviour, natural history and various medic...
Eligibility Criteria
Inclusion
- Confirmed TED (as defined by Bartley and Gorman19)
- \- Eyelid retraction (upper eyelid margin at or above the superior corneoscleral limbus in primary gaze without frontalis muscle contraction) in association with any one of the following:
- Thyroid dysfunction or abnormal regulation (increased serum thyroxine or triiodothyronine level, decreased serum thyroid stimulating hormone level, absence of thyroid radioiodine uptake suppression after administration of triiodothyronine, or the presence of thyroid stimulating immunoglobulins in serum)
- Exophthalmos (Hertel measurement of at least 20mm)
- Extraocular muscle involvement (restrictive myopathy or objective evidence of enlarged muscles)
- Optic nerve dysfunction (abnormal visual acuity, colour vision, pupillary reaction or perimetry not attributable to other causes)
- OR
- \- Thyroid dysfunction or abnormal regulation in association with any one of the following:
- Exophthalmos
- \- Extraocular muscle involvement
- \- Optic nerve dysfunction
- Active disease
- Inflammatory Index
- Inflammatory Index
- Soft tissue feature Rating Chemosis 0 Absent
- Moderate (up to lid margin)
- Severe (over lid margin; persists on closing eye)
- Conjunctival injection 0 Absent 1 Present
- Lid injection 0 Absent
- 1 Present
- Lid edema 0 Absent
- Moderate
- Severe (festoons, overhang)
- Pain at rest (clearly defined as retrobulbar aching) 0 Absent 1 Present
- Pain on movement 0 Absent
- 1 Present
- Total possible 8
- Active disease is defined as an inflammatory index of at least 3 together with acute or subacute onset (3 months and under) and/or evidence of progression (from history or clinical observation).
- (3) Moderate or severe disease
- Primary Criteria
- Mild Moderate Severe Inflammatory Index \<3 3-5 \>5
- Motility \<1/3 1/3 to 2/3 \>2/3 (involving any one muscle) limitation limitation Limitation
- Elevation, depression, adduction and abduction of the individual eyes will be measured with a modified Aimarck perimeter with input from both patient and the orthoptist who performs the test 20.
- Secondary Criteria 21,22,23,24
- Mild Moderate Severe Exophthalmos (mm) \<21 21-24 25 or more
- Best corrected vision (Logmar) - - 0.6 or worse
- CT criterion (Muscle Diameter Index) 21-24 25-30 31 and above
- These criteria are not considered absolutes and emphasize measurable indices based on previous studies.
- The presence of at least 1 primary criterion and at least 1 secondary criterion places the patient in the more advanced disease group (in the situation where 1 primary criterion is mild and the other severe, the presence of 1 severe secondary criterion will yield a severe grade whereas absence of this criterion will result in a mild grade) eg 1) a patient with an inflammatory index of 6 and moderate limitation of extraocular motility, 21mm proptosis, 0.3 vision and MDI of 26 has moderate disease as the secondary criteria for severe disease was not present eg 2) a patient with an inflammatory index of 5 and mild limitation of extraocular motility, 21mm proptosis, 0.3 vision and MDI of 30 has moderate disease as 1 primary and 2 secondary criteria for moderate disease were present eg 3) a patient with inflammatory index of 6 and mild limitation of extraocular motility, 20mm proptosis, 0.3 vision and MDI of 21 has mild disease as the secondary criterion for severe disease was absent and the other primary parameter (motility) was graded mild.
- (4) Age between 21 - 60
- (5) Written informed consent is obtained
Exclusion
- Previous treatment for TED
- Oral steroids (e.g. immunosuppressive dose) for last 3 months, radiotherapy
- Intravenous pulsed steroid or methrotrexate therapy
- Medically unfit to receive I/V high-dose pulsed methylprednisolone or methotrexate
- History of cardiac arrthymias, recent acute myocardial infarction
- History of seizure
- History of acute bleeding peptic ulcer
- History of pulmonary tuberculosis, Hepatitis B carrier, Hepatitis C positivity, HIV
- Uncontrolled diabetes or hypertension (to be eligible for the trial, random blood glucose must be \< 11.1 mmol/L and blood pressure must be 140/90 or lower#. If above these limits, patients can be treated and reviewed at 2 weeks for enrolment when criteria are met - provided the patient does not have optic neuropathy)
- Hepatic dysfunction (Alb, AST, ALT and Alkaline phosphates levels must be within normal range for eligibility)
- Renal impairment (Urea and Creatinine levels must be within normal range)
- Abnormal blood count (outside normal range)
- Others
- Fertile females considering becoming pregnant during the course of the study and those not willing to take precautions to avoid pregnancy
- Both female and male planning to start a family during the trial period or within 6 months of stopping the drugs
- History of seizure
- History of mental / psychiatric disorder
- Patients with clinical features of optic nerve disc pallor at primary presentation will be excluded
Key Trial Info
Start Date :
June 1 2003
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
July 1 2008
Estimated Enrollment :
80 Patients enrolled
Trial Details
Trial ID
NCT00348413
Start Date
June 1 2003
End Date
July 1 2008
Last Update
May 12 2010
Active Locations (1)
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1
Singapore National Centre
Singapore, Singapore, 168751