Thyroid Treatment Trial
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|ClinicalTrials.gov Identifier: NCT00348413|
Recruitment Status : Completed
First Posted : July 4, 2006
Last Update Posted : May 12, 2010
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, parallel, controlled multidisciplinary clinical trial involving Singapore National Eye Centre, National University Hospital, Changi General Hospital, Tan Tock Seng Hospital and University of British Columbia Orbital Services, Singapore Eye Research Institute, Singapore General Hospital Endocrinology and Radiology Departments and Tan Tock Seng Hospital Rheumatology Department is planned. The SingHealth-SGH High Field MR Research Laboratory will be involved in the MR imaging of the trial patients.
Patients who satisfy the inclusion and exclusion criteria will be asked to participate in this trial. After informed consent (Appendix B) is obtained, each patient will be randomized into one of two treatment arms: 1) Intravenous high-dose pulsed methylprednisolone (1 gram infusion over 1 hour per day with a total of 3 doses over 3 days; 4 cycles at 6 weekly intervals) and oral placebo and 2) Intravenous high-dose pulsed methylprednisolone (same dose) plus oral methotrexate 7.5 mg per week for 2 weeks, increased to 10 mg per week for another 2 weeks then 12.5 mg per week for 5 months (total 6 months of methotrexate treatment). Depending on patient response, the dose can be further increased by 2.5mg per week every 4 weeks to a maximum of 20 mg per week. A strict management protocol will be observed for each recruited patient. Patients who develop adverse side effects or need for surgical intervention will receive appropriate treatment (i.e. treatment will deviate from the protocol but will continue to be monitored). Patients who refuse treatment will be observed clinically and with imaging as a natural control group until such time as intervention is accepted.
The patients will have a baseline assessment followed by regular visits to assess treatment response and adverse effects. Observations will include the use of an inflammatory index, motility measurements including quantitative ductions, exophthalmometry readings, palpebral aperture readings and indices of optic nerve function. With regards to the imaging, the patients will be assessed with an initial quantitative CT scan and 3-Tesla MRI scan prior to treatment. After treatment is started, patients will also undergo repeat MRI scan at 24 weeks and 72 weeks to assess quantitative changes with treatment using the Muscle Diameter Index (MDI) and Pixel Value Ratio (PVR) for the inferior rectus, superior rectus, the medial rectus, lateral rectus and orbital fat (Appendix E). Serum and urine will be obtained at the same time intervals as the MRI scan to assess levels of thyroid hormones, thyroid antibodies and urinary glycosaminoglycans (GAGs). Free T4, free T3 and TSH will be recorded to monitor control of hyperthyroidism. Thyroid antibodies measured will include thyroid stimulating immunoglobulin (TSI), thyrotropin-binding inhibition antibody (TB II), thyroid peroxidase antibodies and thyroglobulin antibody. Other tests including the full blood count, urea and electrolytes will be run prior to each dose of steroid treatment and during follow-up to monitor for adverse effects.
The results of the assessments will be analyzed for significant differences in treatment response between the 2 groups. The indices of interest will include the percentage of patients in each group who demonstrate a decrease in the inflammatory index of at least 2 points and the time taken for 50% of patients to show such a decrease. Other parameters that reflect the visual function and motility will be compared at different points in time after starting treatment to observe response and sustainability of response. From the serial MRI scans, quantitative analysis of orbital tissues will be done to identify changes with treatment. Antibody and GAG levels will be analyzed to detect any change with treatment. The types and frequency of adverse side effects in the 2 groups will also be assessed.
80 normal subjects will be recruited for MRI scan of the orbits and brain to obtain normative values for the MDI and PVR for the Asian population (Appendix E). This will include 20 subjects from each of 4 decades (21-30 years, 31-40 years, 41-50 years, 51-60 years).
The normative data will also be used to create a virtual orbital atlas. This aspect of the study will be performed in collaboration with the Labs for Information Technology (A-Star).
|Condition or disease||Intervention/treatment||Phase|
|Graves Ophthalmopathy||Drug: Intravenous Methylprednisolone + Oral Methotrexate vs Intravenous Methylprednisolone + Placebo||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Official Title:||Comparison of Efficacy and Safety of Intravenous Pulsed Methylprednisolone and Oral Methotrexate Versus Intravenous Pulsed Methylprednisolone and Oral Placebo in the Treatment of Active Moderate and Severe Thyroid Eye Disease - a Prospective, Randomized, Double-blind, Parallel, Controlled Multidisciplinary Clinical Trial and Imaging Study.|
|Study Start Date :||June 2003|
|Actual Primary Completion Date :||July 2008|
|Actual Study Completion Date :||July 2008|
- Inflammatory index
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00348413
|Singapore National Centre|
|Singapore, Singapore, 168751|
|Study Chair:||Lay Leng Seah, MMed(Ophth), FRCS(Ed)||Singapore National Eye Centre|
|Principal Investigator:||Audrey Lee Geok Looi, MMed(Ophth), FRCS(Ed)||Singapore National Eye Centre|
|Principal Investigator:||Jack Rootman, MD. FRCS(C)||University of British Columbia|