The Effect of a New Antioxidant Combination (ASTED) on Moderate to Severe Thyroid Eye Disease

Study Overview
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Brief Summary
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ASTED (Antioxidant Supplements for TED) trial is an investigator-initiated, randomized, triple masked, clinical trial of a selected combination of vitamins and minerals versus placebo in patients with moderate to severe thyroid eye disease. The trial has a parallel-arm design.

Detailed Description
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Primary aim: To investigate if ASTED or as compared with placebo could affect the course of TED either by enhancing improvement or preventing worsening in patients with Moderate to severe TED thyroid eye disease (TED) based on: Total eye score (NOSPECS severity score) 1 Total eye score is used to assess the severity of TED, which was calculated by multiplying each class of the NOSPECS system1 (except class 0) to its grade of severity (0-3), yielding a maximum total score of 63 and a minimum total score of 0 (the higher the number the worse the severity) The overall ophthalmic outcome is a composite score based on multiple items (Soft tissue, retraction, proptosis, diplopia, and corneal involvement); the use of a composite score circumvents the problem arising from the presence of improvement in one item and simultaneous worsening in another item. The severity score in each of the classes 1, 2, 3, and 4 will also be separately compared to evaluate the effect of different treatments on each sign. Score of thyroid eye disease Quality of life questionnaire (TED-QOL) 2. Secondary outcomes measures: To compare possible change in: Clinical activity score (CAS Score) 3 (7 items are scored in the beginning and 10 items are scored at 3 and 6 months) Serum thyroid auto-antibodies (Anti-thyroid peroxidase (TPO), Anti-thyroglobulin) at 0, 3 and 6 months. Thyroid function test (Free T4, T3, and TSH) will be measured in all 3 visits0 Side effects

Official Title
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The Effect of a New Antioxidant Combination (ASTED) on Moderate to Severe Thyroid Eye Disease, a Double Blind Placebo Controlled Randomized Clinical Trial

Conditions
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Thyroid Eye Disease

Intervention / Treatment
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* Drug: Methylprednisolone + ASTED
* Drug: Methylprednisolone +Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Moderate to severe TED of less than 18 months duration: Active state (Clinical activity score of 3 and more). No steroid and or any supplement treatment for the last 6 months. Euthyroidism Age 18-70 years. Exclusion Criteria: Sight-threatening TED Pregnancy Drug and/or alcohol abuse Severe concomitant illness Inability to comply with the study protocol No informed consent Developing more severe TED (Sight threatening TED) in the course of the trial. Contraindications of steroid treatment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Methylprednisolone + ASTED<br>ASTED (Antioxidant Supplements for Thyroid Eye Disease) includes : B-Carotene (6 mg)+ Vit.C (200 mg) + Vit.E (200 mg) + Nicotinamide(20mg) + Selenium(200mic.) + Zinc oxide (8 mg) + Copper gluconate or oxide (1mg) + Manganese chloride (1.8 mg), Twice a day for 6 months Methylprednisolone includes : Methylprednisolone tablet of 50 and 5 mg, company….) 1mg/kg for the first 2 weeks, 0.8mg/kg for 2 weeks, 0.7 mg/kg for 2 weeks, and then tapering off the methylprednisolone in 6 weeks (total duration of 12 weeks) by 8-10 mg per week. For example, a patient with 75 kg weight will receive 75 mg for 2 weeks, 60 mg for 2 weeks, 52.5 mg for 2 weeks, and then decreasing by 8-10 mg per week for 6 weeks. The dose regiment will be written and handed to the patient on the first visit and will be monitored during the follow up. | Drug: Methylprednisolone + ASTED<br>* ASTED tablet: Twice daily for 6 months Methylprednisolone: Methylprednisolone tablet of 50 and 5 mg, company….) 1mg/kg for the first 2 weeks, 0.8mg/kg for 2 weeks, 0.7 mg/kg for 2 weeks, and then tapering off the methylprednisolone in 6 weeks (total duration of 12 weeks) by 8-10 mg per week. For example, a patient with 75 kg weight will receive 75 mg for 2 weeks, 60 mg for 2 weeks, 52.5 mg for 2 weeks, and then decreasing by 8-10 mg per week for 6 weeks. The dose regiment will be written and handed to the patient on the first visit and will be monitored during the follow ups.<br>|
| Placebo Comparator: Methylprednisolone + Placebo<br>Placebo Twice a day for 6 months Methylprednisolone prescribes as the same as arm 1 | Drug: Methylprednisolone +Placebo<br>* Placebo: twice daily Methylprednisolone: Methylprednisolone tablet of 50 and 5 mg, company….) 1mg/kg for the first 2 weeks, 0.8mg/kg for 2 weeks, 0.7 mg/kg for 2 weeks, and then tapering off the methylprednisolone in 6 weeks (total duration of 12 weeks) by 8-10 mg per week. For example, a patient with 75 kg weight will receive 75 mg for 2 weeks, 60 mg for 2 weeks, 52.5 mg for 2 weeks, and then decreasing by 8-10 mg per week for 6 weeks. The dose regiment will be written and handed to the patient on the first visit and will be monitored during the follow ups.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of total eye score changes (using NOSPECS severity score) | Total eye score change during study | baseline, 1 month, 3 months, 6 months | 
| Mean of thyroid eye disease Quality of life score changes (Using TED-QOL) | Changing quality of life during study period | baseline, 1 month, 3 months, 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean of clinical activity score changes (CAS Score) | Change of clinical activity score during study period | baseline, 1 month, 3 months, 6 months | 
| Changes of serum thyroid auto-antibodies (Anti-thyroid peroxidase (TPO), Anti-thyroglobulin) | Change of serum thyroid auto-antibodies during study period | baseline, 1 month, 3 months, 6 months | 
| Changes of thyroid function test (Free T4, T3, and TSH) Levels | Change of thyroid function test during study period | baseline, 1 month, 3 months, 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antioxidant, Graves' ophthalmopathy, Activity, Severity