99Tc-MDP for Thyroid-Associated Ophthalmopathy

Study Overview
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Brief Summary
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To investigate the efficacy，safety and tolerability of 99Tc-MDP in comparison to Methylprednisolone, in the treatment of participants suffering from active moderate to severe TAO.

Official Title
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A Double-masked, Methylprednisolone-control, Efficacy and Safety Study of 99Tc-MDP for Thyroid Associated Ophthalmopathy.

Conditions
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Thyroid-Associated Ophthalmopathy

Intervention / Treatment
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* Drug: Methylprednisolone
* Drug: 99Tc-MDP(99Technetium-Methylenediphosphonate Injection)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient age 18 Years to 76 Years; Fewer than 6 months from onset of TAO; Clinical diagnosis of Graves' disease associated with active TAO and a clinical activity score of ≥ 3; Moderate to severe TAO; No previous medical or surgical treatment, excluding local supportive measures and oral steroids if the maximum cumulative dose is less than 1000 mg methylprednisolone or equivalent with at least 6 weeks between last administration of oral steroids and randomization. Exclusion Criteria: Optic neuropathy, severe orbital appearance and surgical; Extra-thyroid disease; Pregnant and children; Severe impairment of cardiac, hepatic and renal functions; Allergies; Other contraindications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 76 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Methylprednisolone(ivMP)<br>Methylprednisolone(ivMP) 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. once a week for 6 weeks. | Drug: Methylprednisolone<br>* 500mg i.v. infusion once a week for 6 weeks followed by 250mg i.v. once a week for 6 weeks.<br>|
| Experimental: 99Tc-MDP<br>99Tc-MDP 15mg i.v. infusion once a day for 10 days, 20 days apart, received 3 courses of infusions. | Drug: 99Tc-MDP(99Technetium-Methylenediphosphonate Injection)<br>* 15mg i.v. infusion once a day for 10 days, 20 days apart, received 3 courses of infusions.<br>* Other names: Yunke;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responder Status at Week 12 | This end point main evaluation improvement of clinical activity score and proptosis at week 12. A reduction of the CAS 2 point or more, and reduction of the proptosis 2 mm or more was defined as response. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Average Continuous Change in CAS From Baseline to Week 24 | The 7-item European Group on Graves' Ophthalmopathy (EUGOGO) amended CAS was used to evaluate clinical activity. CAS of 3 point or more on a 7-point scale indicating active thyroid-associated ophthalmopathy. | Baseline to Week 24 | 
| Overall Average Continuous Change in Proptosis From Baseline to Week 24 | Proptosis is the amount of protrusion of the eye from the orbital rim. Measurements were recorded with the Hertel exophthalmometer. | Baseline to Week 24 | 
| Overall Average Change in Diplopia grading From Baseline to Week 24 | Diplopia grading included 01/4no：no diplopia; 11/4intermittent： diplopia in primary position of gaze, when tired or when first awakening; 21/4inconstant： diplopia at extremes of gaze; 31/4constant： continuous diplopia in primary or reading position). Diplopia change in one grade or more at week 24 was regarded as improvement. | Baseline to Week 24 | 
| Overall Average Change in extra-ocular muscular thickening From Baseline in thickening extra-ocular muscular improvement in Orbital CT to Week 24 | Observation of extra-ocular muscular thickening is observed on Orbital CT. One or more extra-ocular muscle recovery at week 24 was regarded as improvemed. | Baseline to Week 24 | 
| Overall Average Change in Graves' Ophthalmopathy Quality of Life (GO-QOL) Scale From baseline to Week 24 follow-up | The GO-QOL is a 16-item self-administered questionnaire used to assess the perceived effects of thyroid associated ophthalmopathy (TAO) by the participants on their daily physical and psychosocial functioning. Two subscales of the 16-question GO-QOL have been defined: Visual Functioning and Appearance, with 8 questions comprising each subscale.The transformed overall score is the sum of scores from all 16 questions to a scale of 0 (worst health) to 100 (best health). A change of 8 point was defined as improvement. | Baseline to Week 24 | 
| Overall Average Change in GO-QOLScale - Visual Functioning From baseline to Week 24 follow-up | Transformed Visual Functioning score is the sum of scores from following 8 questions to a scale of 0 (worst health) to 50 (best health): bicycling, driving, moving around the house, walking outdoors, reading, watching television (TV), hobby or pastime, feel hindered. | Baseline to Week 24 | 
| Overall Average Change in GO-QOLScale - Appearance From baseline to Week 24 follow-up | Transformed Appearance score is the sum of scores from the following 8 questions to a scale of 0 (worst health) to 50 (best health): feel appearance has changed, feel being stared at, feel people react unpleasantly, influence on self-confidence, feel socially isolated, influence on making friends, appear less often on photos, try to mask changes in appearance. | Baseline to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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99Tc-MDP, TAO, efficacy, safety