Function of Regulatory T Cells Improved by Dexamethasone in Graves' Patients

Study Overview
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Brief Summary
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Antithyroid drugs is the first choice treatment of Graves' disease in China and Europe. However,the relapse rate is very high (40-60%) after therapy withdrawal, and many patients need further treatment. In our previous study, a new treatment strategy for GD has been introduced. After methimazole (18 months) combined with intrathyroid injection of dexamethasone (DEX) (3 months) treatment, the relapse rate of hyperthyroidism was markedly reduced compared with methimazole treatment alone (7.4% versus 51%) during the 2-year follow-up period. The results have been published in the 'J Clin Endocrinol Metab, 2009,94:4984-4991'. However, the mechanism by which the DEX reduces the relapse rate of GD is not fully understood. In vitro study, we have proven that DEX could effectively improve the function of regulatory T (Treg) cells and set up a new balance of T helper 1(Th1)/Th2 in GD patients(this results have been in press in the Eur J Endocrinol). In order to elucidate mechanism of this treatment strategy in vivo, we plan to recruit 20-30 patients with GD and treat those patients by intrathyroid injection of DEX combined with methimazole, and the function of Treg cells and balance of Th1/Th2 will be evaluated.

Official Title
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Function of Regulatory T Cells Improved by Treatment With an Intrathyroid Injection of Dexamethasone in Graves' Patients

Conditions
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Graves' Disease

Intervention / Treatment
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* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: GD patients will have been trated with methimazole and serum levels of TSH and FT4 should be in the normal range. Exclusion Criteria: Pregnancy Allergy to antithyroid drugs (ATD) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels more than two times the upper normal range Patients with coexistent endocrine or organ-specific autoimmune diseases (such as those with atopic dermatitis or bronchial asthma) Patients taking medications that could affect the immune system (such as corticosteroids), noncompliance because of psychiatric or other serious diseases Unwillingness to participate in the study.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 60 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
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Isotonic Na chloride<br>The treatment strategy is the same with intervention, only the drug (dexamethasone) will be changed to isotonic Na chloride. | Drug: Dexamethasone<br>* The course of treatment will be last for 3 months. The intrathyroid injection of dexamethasone will be performed using a 25-gauge (0.25-mm) needle under ultrasound guidance. The injection will be performed in both lobes of the thyroid. The dosage of dexamethasone is 5mg (1.0 ml) in each lobe, twice a week during the first month of the treatment. The treatment strategy will be changed to once a week in the second month and twice a month in the third month; the dosage of dexamethasone is the same as in the first month.<br>* Other names: Hexadecadrol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Function of Regulatory T Cells | Function of Treg cells will be analyzed by the proliferation rate of CD4+CD25- T cells, according to the following formula: cell proliferation rate (%) = proliferation rate of CD4+CD25- T cells co-cultured with CD4+CD25+T cells/proliferation rate of CD4+CD25- T cells alone×100%. | From baseline to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of Th1 and Th2 cells | Th1 and Th2 cells will be identified by flow cytometry analysis. | From baseline to 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexamethasone, Graves' disease, Function of regulatory T cells, The proportion of Th1 and Th2 cells