The Effects of Metformin in Patients With Mild Graves' Ophthalmopathy

Study Overview
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Brief Summary
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This is a prospective, randomized, double-blind, placebo-controlled study about the effect of metformin in patients with mild Graves' ophthalmopathy. Eighty patients with mild ophthalmopathy will be included. Each patient will be given either metformin (500mg PO three times a day) or placebo ( PO three times a day ) for 6 months and then followed for 6 months after withdrawal of treatment.

Conditions
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Mild Graves' Ophthalmopathy

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-80 years Patients should not have diabetes (HbA1c level at screening should be lower than 6.5) Mild Graves' ophthalmopathy according to EUGOGO statement. Clinical activity score lower than 4 Being euthyroid for at least 2 month before the enrollment No previous specific therapy for GO in 6 month before the enrollment except for local measures (e.g. eye drops) Exclusion Criteria: Moderate-severe Graves' ophthalmopathy Clinical activity score ≥ 4 Contraindication for metformin use as following: renal dysfunction (creatinine level should be within normal range), liver dysfunction (AST and ALT levels should be within normal range), severe concomitant illness Pregnant women Current use of metformin or containing preparations Metformin intolerance Inability to comply with the study protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin<br>Metformin 500mg PO three times a day for 24 weeks | Drug: Metformin<br>* Tablets metformin 500 mg PO three times a day for 24 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo tab. PO three times a day for 24 weeks | Drug: Placebo<br>* Tablets placebo PO three times a day for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Clinical Activity Score (CAS) score | Comparison of CAS scores before and after treatment in each arm and an inter-arm | At 0, 6 and 12 months | 
| Change of NOSPECS score | Comparison of NOSPECS scores before and after treatment in each arm and an inter-arm. | At 0, 6 and 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events | Comparison of adverse events rate in each arm and an inter-arm. | At 0, 6 and 12 months | 
| Quality of life questionnaires (GO-QoL) | Comparison of Graves' ophthalmopathy Quality of life questionnaire (GO-QOL) scores before and after treatment in each arm and an inter-arm. | At 0, 6 and 12 months |